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We present 14 simultaneous Chandra X-ray Observatory (CXO)-Hubble Space Telescope (HST) observations of Jupiter's Northern X-ray and ultraviolet (UV) aurorae from 2016 to 2019. Despite the variety of dynamic UV and X-ray auroral structures, one region is conspicuous by its persistent absence of emission: the dark polar region (DPR). Previous HST observations have shown that very little UV emission is produced by the DPR. We find that the DPR also produces very few X-ray photons. For all 14 observations, the low level of X-ray emission from the DPR is consistent (within 2-standard deviations) with scattered solar emission and/or photons spread by Chandra's Point Spread Function from known X-ray-bright regions. We therefore conclude that for these 14 observations the DPR produced no statistically significant detectable X-ray signature.
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OBJECTIVE: The prevalence of radiographic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) approaches 50%, yet the prevalence of significant knee pain is unknown. We applied three different models of Knee injury and Osteoarthritis Outcome Score (KOOS) thresholds for significant knee pain to an ACLR cohort to identify prevalence and risk factors. DESIGN: Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort patients with a unilateral primary ACLR and normal contralateral knee were assessed at 2 and 6 years. Independent variables included patient demographics, validated Patient Reported Outcomes (PRO; Marx activity score, KOOS), and surgical characteristics. Models included: (1) KOOS criteria for a painful knee = quality of life subscale <87.5 and ≥2 of: KOOSpain <86.1, KOOSsymptoms <85.7, KOOSADL <86.8, or KOOSsports/rec <85.0; (2) KOOSpain subscale score ≤72 (≥2 standard deviations below population mean); (3) 10-point KOOSpain drop from 2 to 6 years. Proportional odds models (alpha ≤ 0.05) were used. RESULTS: 1761 patients of median age 23 years, median body mass index (BMI) 24.8 kg/m(2) and 56% male met inclusion, with 87% (1530/1761) and 86% (1506/1761) follow-up at 2 and 6 years, respectively. At 6 years, n = 592 (39%), n = 131 (9%) and n = 169 (12%) met criteria for models #1 through #3, respectively. The most consistent and strongest independent risk factor at both time-points was subsequent ipsilateral knee surgery. Low 2-year Marx activity score increased the odds of a painful knee at 6 years. CONCLUSIONS: Significant knee pain is prevalent after ACLR; with those who undergo subsequent ipsilateral surgery at greatest risk. The relationship between pain and structural OA warrants further study.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Artralgia/epidemiologia , Traumatismos do Joelho/cirurgia , Osteoartrite do Joelho/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort. METHODS: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors. RESULTS: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference. CONCLUSION: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study.
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Reconstrução do Ligamento Cruzado Anterior , Traumatismos em Atletas/cirurgia , Traumatismos do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Adolescente , Adulto , Fatores Etários , Traumatismos em Atletas/complicações , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Traumatismos do Joelho/complicações , Articulação do Joelho/cirurgia , Modelos Lineares , Estudos Longitudinais , Masculino , Meniscos Tibiais/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Radiografia , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
The magnetospheric cusp connects the planetary magnetic field to interplanetary space, offering opportunities for charged particles to precipitate to or escape from the planet. Terrestrial cusps are typically found near noon local time, but the characteristics of the Jovian cusp are unknown. Here we show direct evidence of Jovian cusps using datasets from multiple instruments onboard Juno spacecraft. We find that the cusps of Jupiter are in the dusk sector, which is contradicting Earth-based predictions of a near-noon location. Nevertheless, the characteristics of charged particles in the Jovian cusps resemble terrestrial and Saturnian cusps, implying similar cusp microphysics exist across different planets. These results demonstrate that while the basic physical processes may operate similarly to those at Earth, Jupiter's rapid rotation and its location in the heliosphere can dramatically change the configuration of the cusp. This work provides useful insights into the fundamental consequences of star-planet interactions, highlighting how planetary environments and rotational dynamics influence magnetospheric structures.
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We present a statistical study of Jupiter's disk X-ray emissions using 19 years of Chandra X-Ray Observatory (CXO) observations. Previous work has suggested that these emissions are consistent with solar X-rays elastically scattered from Jupiter's upper atmosphere. We showcase a new pulse invariant (PI) filtering method that minimizes instrumental effects which may produce unphysical trends in photon counts across the nearly two-decade span of the observations. We compare the CXO results with solar X-ray flux data from the Geostationary Operational Environmental Satellites X-ray Sensor for the wavelength band 1-8 Å (long channel), to quantify the correlation between solar activity and Jovian disk counts. We find a statistically significant Pearson's Correlation Coefficient of 0.9, which confirms that emitted Jovian disk X-rays are predominantly governed by solar activity. We also utilize the high spatial resolution of the High Resolution Camera Instrument on-board the CXO to map the disk photons to their positions on Jupiter's surface. Voronoi tessellation diagrams were constructed with the Juno Reference Model through Perijove 9 internal field model overlaid to identify any spatial preference of equatorial photons. After accounting for area and scattering across the curved surface of the planet, we find a preference of Jovian disk emission at 2-3.5 Gauss surface magnetic field strength. This suggests that a portion of the disk X-rays may be linked to processes other than solar scattering: the spatial preference associated with magnetic field strength may imply increased precipitation from the radiation belts, as previously postulated.
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AIM: Hypoxia causes vasodilatation of coronary arteries which protects the heart from ischaemic damage through mechanisms including the generation of hydrogen sulphide (H2 S), but the influence of the perivascular adipose tissue (PVAT) and myocardium is incompletely understood. This study aimed to determine whether PVAT and the myocardium modulate the coronary artery hypoxic response and whether this involves hydrogen sulphide. METHODS: Porcine left circumflex coronary arteries were prepared as cleaned segments and with PVAT intact, myocardium intact or both PVAT and myocardium intact, and contractility investigated using isometric tension recording. Immunoblotting was used to measure levels of H2 S-synthesizing enzymes: cystathionine-ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MPST). RESULTS: All three H2 S-synthesizing enzymes were detected in the artery and myocardium, but only CBS and MPST were detected in PVAT. Hypoxia elicited a biphasic response in cleaned artery segments consisting of transient contraction followed by prolonged relaxation. In arteries with PVAT intact, hypoxic contraction was attenuated and relaxation augmented. In arteries with myocardium intact, hypoxic contraction was attenuated, but relaxation was unaffected. In replacement experiments, replacement of dissected PVAT and myocardium attenuated artery contraction and augmented relaxation to hypoxia, mimicking the effect of in situ PVAT and indicating involvement of a diffusible factor(s). In arteries with intact PVAT, augmentation of hypoxic relaxation was reversed by amino-oxyacetate (CBS inhibitor), but not DL-propargylglycine (CSE inhibitor) or aspartate (inhibits MPST pathway). CONCLUSION: PVAT augments hypoxic relaxation of coronary arteries through a mechanism involving H2 S and CBS, pointing to an important role in regulation of coronary blood flow during hypoxia.
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Tecido Adiposo/enzimologia , Vasos Coronários/metabolismo , Cistationina beta-Sintase/metabolismo , Sulfeto de Hidrogênio/metabolismo , Miocárdio/enzimologia , Vasodilatação , Animais , Hipóxia Celular , Circulação Coronária , Cistationina gama-Liase/metabolismo , Feminino , Gases , Técnicas In Vitro , Masculino , Comunicação Parácrina , Transdução de Sinais , Sulfurtransferases/metabolismo , Sus scrofaRESUMO
BACKGROUND AND PURPOSE: Noradrenaline and ATP are sympathetic co-transmitters. In the rat perfused mesenteric bed cannabinoids have been shown to modify the overall response to sympathetic nerve stimulation. This study has assessed whether cannabinoid receptor activation modulates differentially the noradrenergic and purinergic components of sympathetic vasoconstriction. EXPERIMENTAL APPROACH: Rat mesenteric beds were perfused with physiological salt solution and the effects of cannabinoids on responses to nerve stimulation, or exogenous noradrenaline or alpha,beta-methylene ATP (alpha,beta-meATP; P2X receptor agonist) were determined after raising tone with U46619. The effects of cannabinoids on the noradrenaline and ATP components of sympathetic neurotransmission were assessed using the alpha 1-adrenoceptor antagonist, prazosin, or after P2X receptor desensitization with alpha,beta-meATP. KEY RESULTS: Anandamide, WIN 55,212-2 and CP55,940 attenuated sympathetic neurogenic vasoconstrictor responses. The inhibitory actions of anandamide and WIN 55,212-2 were blocked by LY320135, a CB1 receptor antagonist, but not by SR144528, a CB2 receptor antagonist. The inhibitory actions of CP55,940 were unaffected by LY320135 and SR144528. WIN 55,212-3, the inactive S(-) enantiomer of WIN 55,212-2, had no effect on sympathetic neurogenic responses. None of the cannabinoids affected contractile responses to exogenous noradrenaline or alpha,beta-meATP. Anandamide and WIN 55,212-2 inhibited both the noradrenaline and ATP components of the sympathetic neurogenic contractile responses, with effects on the ATP component being most marked. CONCLUSIONS AND IMPLICATIONS: These results indicate that prejunctional CB1-like receptors mediate the sympathoinhibitory action of anandamide and WIN 55,212-2, but not CP55,940, in the rat mesenteric bed. Cannabinoids inhibit both the noradrenergic and purinergic components of sympathetic neurotransmission.
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Trifosfato de Adenosina/análogos & derivados , Canabinoides/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Norepinefrina/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Trifosfato de Adenosina/farmacologia , Fibras Adrenérgicas/efeitos dos fármacos , Fibras Adrenérgicas/fisiologia , Animais , Ácidos Araquidônicos/farmacologia , Benzofuranos/farmacologia , Benzoxazinas/farmacologia , Canfanos/farmacologia , Cicloexanóis/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Endocanabinoides , Técnicas In Vitro , Masculino , Artérias Mesentéricas/inervação , Artérias Mesentéricas/fisiologia , Morfolinas/farmacologia , Tono Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/inervação , Músculo Liso Vascular/fisiologia , Naftalenos/farmacologia , Perfusão , Alcamidas Poli-Insaturadas/farmacologia , Prazosina/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptores Purinérgicos P2/fisiologiaRESUMO
Hypoxia-induced coronary artery vasodilatation protects the heart by increasing blood flow under ischemic conditions, however its mechanism is not fully elucidated. Hydrogen sulfide (H2S) is reported to be an oxygen sensor/transducer in the vasculature. The present study aimed to identify and characterise the role of H2S in the hypoxic response of the coronary artery, and to define the H2S synthetic enzymes involved. Immunoblotting and immunohistochemistry showed expression of all three H2S-producing enzymes, cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST), in porcine coronary artery. Artery segments were mounted for isometric tension recording; hypoxia caused a transient endothelium-dependent contraction followed by prolonged endothelium-independent relaxation. The CBS inhibitor amino-oxyacetate (AOAA) reduced both phases of the hypoxic response. The CSE inhibitor dl-propargylglycine (PPG) and aspartate (limits MPST) had no effect alone, but when applied together with AOAA the hypoxic relaxation response was further reduced. Exogenous H2S (Na2S and NaHS) produced concentration-dependent contraction followed by prolonged relaxation. Responses to both hypoxia and exogenous H2S were dependent on the endothelium, NO, cGMP, K+ channels and Cl-/HCO3- exchange. H2S production in coronary arteries was blocked by CBS inhibition (AOAA), but not by CSE inhibition (PPG). These data show that H2S is an endogenous mediator of the hypoxic response in coronary arteries. Of the three H2S-producing enzymes, CBS, expressed in the vascular smooth muscle, appears to be the most important for H2S generated during hypoxic relaxation of the coronary artery. A contribution from other H2S-producing enzymes only becomes apparent when CBS activity is inhibited.
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Vasos Coronários/efeitos dos fármacos , Cistationina beta-Sintase/metabolismo , Sulfeto de Hidrogênio/farmacologia , Sulfetos/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Hipóxia Celular , Células Cultivadas , Antiportadores de Cloreto-Bicarbonato/efeitos dos fármacos , Antiportadores de Cloreto-Bicarbonato/metabolismo , Vasos Coronários/enzimologia , GMP Cíclico/metabolismo , Cistationina beta-Sintase/antagonistas & inibidores , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/metabolismo , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Sulfeto de Hidrogênio/metabolismo , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Óxido Nítrico/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Transdução de Sinais , Sulfetos/metabolismo , Sulfurtransferases/metabolismo , Sus scrofa , Vasodilatadores/metabolismoRESUMO
In this study we examined the structural properties of cerebral and mesenteric resistance arteries isolated from normotensive, Sprague-Dawley (SD) rats (mean arterial pressure [MAP], 110 +/- 3 mm Hg) and hypertensive, transgenic (TG) rats (MAP, 167 +/- 4 mm Hg), which express the mouse Ren-2 renin gene. Vessels were set up in a pressure myograph, and ID and vascular wall thickness were determined at increasing intraluminal pressures. Arteries were subsequently pressurized to the MAP of the animal from which they were isolated and were fixed with glutaraldehyde before being embedded in araldite, sectioned, and examined histologically. The middle cerebral artery (MCA) isolated from SD rats and TG rats had similar media cross-sectional areas. There was no difference in MCA diameter at 10 mm Hg in vessels from TG rats compared with SD rats. However, at higher distending pressures, the diameter of the MCA from TG rats was significantly smaller than that of vessels from SD rats. This reduced ID at the higher pressures was a consequence of a decreased distensibility of the MCA from TG rats (as shown by a leftward shift of the stress-strain relationship in arteries from TG rats) and was not caused by an increase in wall thickness. First- and second-order mesenteric resistance arteries isolated from TG rats displayed an increased wall thickness and media content compared with vessels from SD rats. However, this alteration in mesenteric artery structure did not impinge on the ID of arteries from TG rats; there was no difference in the IDs of mesenteric resistance arteries between the two strains at any distending pressure. These observations show that there are distinct regional alterations in vascular structure in hypertensive TG rats expressing the mouse Ren-2 renin gene. Mesenteric resistance arteries isolated from TG rats display signs of vascular growth, although this structural alteration does not produce a reduction in the ID of these arteries per se. In contrast, cerebral arteries from TG rats do not show increased growth but have a reduced vascular distensibility, which results in a smaller ID compared with vessels from SD rats.
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Artérias Cerebrais/fisiopatologia , Hipertensão/fisiopatologia , Artérias Mesentéricas/fisiopatologia , Renina/fisiologia , Resistência Vascular/fisiologia , Animais , Animais Geneticamente Modificados , Pressão Sanguínea , Expressão Gênica , Hipertensão/genética , Camundongos , Ratos , Ratos Sprague-Dawley , Renina/genéticaRESUMO
In this study we examined the structural and functional properties of mesenteric resistance arteries isolated from normotensive and hypertensive vasopressin-deficient rats. Hypertensive rats had a significantly higher mean arterial pressure (176 +/- 3 mm Hg) than normotensive controls (121 +/- 2 mm Hg). First- and second-order mesenteric resistance arteries were set up in a pressure myograph and pressurized to the mean arterial pressure of the rat from which they had been isolated. Vessels were fixed with glutaraldehyde, embedded in Araldite, sectioned, and examined histologically. First- and second-order mesenteric resistance arteries from hypertensive rats displayed a reduced internal diameter and increased media-to-lumen ratio compared with their normotensive controls. However, there was no evidence for an increased media content, indicating that the reduced internal diameter of hypertensive arteries was consequent to either remodeling of similar amounts of wall material or a reduced artery distensibility but not vascular growth. Pressurized arteries were also examined with respect to their responsiveness to the vasoconstrictors norepinephrine and arginine vasopressin and to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator papaverine. Both first- and second-order mesenteric arteries from hypertensive rats displayed enhanced sensitivity to norepinephrine compared with their normotensive controls. This effect was specific for norepinephrine, because responses to arginine vasopressin were similar in vessels isolated from normotensive and hypertensive rats. No evidence was found for an impaired endothelium-dependent vasodilatation in arteries from hypertensive rats. Indeed, in hypertensive vasopressin-deficient rats responses to acetylcholine were increased in first-order arteries compared with those from normotensive rats. Responses to papaverine were similar in arteries isolated from either normotensive or hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hipertensão/fisiopatologia , Artérias Mesentéricas/fisiopatologia , Vasopressinas/deficiência , Animais , Hipertensão/genética , Hipertensão/patologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/patologia , Microcirculação/patologia , Norepinefrina/farmacologia , Papaverina/farmacologia , Ratos , Resistência VascularRESUMO
OBJECTIVE: To examine the effects of hypertension induced by chronic inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME) on the structure of mesenteric resistance arteries. DESIGN AND METHODS: Brattleboro rats were given L-NAME (0.01-0.05 mg/ml, equivalent to 10-50 mg/kg per day) in their drinking water for 2-3 weeks. On the day of the experiment, mean arterial pressure was measured directly using an intra-arterial catheter that had been implanted 2 days previously. Isolated mesenteric resistance arteries were set up in a pressure-perfusion myograph in a calcium-free physiological solution and subsequently fixed with glutaraldehyde, embedded in Araldite, sectioned and examined histologically. RESULTS: L-NAME administration increased mean arterial blood pressure in comparison with normotensive controls. No differences were found between the structural characteristics of mesenteric resistance arteries of first (pressurized diameter approximately 350 microns), second (approximately 270 microns) or third (approximately 200 microns) order vessels isolated from normotensive rats and rats that had been treated with L-NAME. There were no significant correlations between mean arterial blood pressure and the variables of internal diameter, media thickness and media: lumen area ratio. CONCLUSIONS: Hypertension produced by chronic inhibition of nitric oxide synthase is not associated with remodelling of mesenteric resistance arteries in Brattleboro rats.
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Hipertensão/fisiopatologia , Artérias Mesentéricas/fisiopatologia , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Masculino , Miografia , NG-Nitroarginina Metil Éster , Ratos , Ratos Brattleboro , Televisão , Fatores de Tempo , Resistência Vascular/efeitos dos fármacosRESUMO
Under normal experimental conditions, sympathetic nerve-mediated responses to electrical field stimulation in the isolated distal saphenous artery of the rabbit are sensitive to prazosin (0.1 microM) and so, by definition, are mediated by alpha 1-adrenoceptors. In the presence of angiotensin II (A II, 0.05 microM) however, a component of the response to nerve stimulation became resistant to prazosin. This 'uncovered' response was virtually abolished by the selective alpha 2-adrenoceptor antagonist rauwolscine (1 microM), a concentration that in the absence of A II had enhanced nerve-mediated responses. Exposure to A II therefore, allows the clear demonstration of a role for postjunctional alpha 2-adrenoceptors in mediating the contractile response to sympathetic nerve stimulation in this arterial preparation.
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Angiotensina II/farmacologia , Músculo Liso Vascular/inervação , Receptores Adrenérgicos alfa/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Estimulação Elétrica , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Norepinefrina/farmacologia , Prazosina/farmacologia , Coelhos , Sistema Nervoso Simpático/fisiologia , Ioimbina/farmacologiaRESUMO
1. Intracellular recording was used to investigate the electrophysiological effects of activating peptidergic primary afferent axons with capsaicin in the smooth muscle of rat mesenteric arteries in vitro. In addition, continuous amperometry was used to monitor the effects of capsaicin on noradrenaline release from the sympathetic nerves. 2. Capsaicin (1 microm) produced a hyperpolarization (-11+/-2 mV) and a reduction in the time constant of decay of excitatory junction potentials (e.j.p.'s) evoked by electrical stimulation of the perivascular sympathetic nerves. These effects of capsaicin were mimicked by calcitonin gene-related peptide (CGRP; 1 and 10 nm) but not by substance P (50 nm), which produced a small hyperpolarization (maximum -3+/-1 mV) but did not change excitatory junction potential (e.j.p.) time course. 3. The hyperpolarization produced by capsaicin and CGRP was blocked by glibenclamide (10 microm) but was not changed by the CGRP antagonist, CGRP8-37 (0.5 microm). Mechanical denudation of the endothelium also did not reduce the effect of capsaicin on membrane potential. 4. Capsaicin (1 microm) increased the amplitude of e.j.p.'s. This effect was not mimicked by CGRP or substance P nor blocked by glibenclamide or CGRP8-37. 5. All effects of capsaicin desensitized. 6. Capsaicin (1 microm) had no effect on noradrenaline-induced oxidation currents evoked by electrical stimulation, indicating that noradrenaline release was unchanged. 7. These results suggest that CGRP released from primary afferent axons hyperpolarizes vascular smooth muscle by activating glibenclamide-sensitive K+ channels. The findings also indicate that an unknown factor released by the primary afferent axons increases e.j.p. amplitude.
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Capsaicina/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Animais , Apamina/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Estimulação Elétrica , Eletrofisiologia , Endotélio Vascular/fisiologia , Feminino , Glibureto/farmacologia , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Artérias Mesentéricas/inervação , Artérias Mesentéricas/fisiologia , Neurônios Aferentes/metabolismo , Neurônios Aferentes/fisiologia , Norepinefrina/farmacologia , Fragmentos de Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar , Substância P/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologiaRESUMO
In the rabbit isolated distal saphenous artery, the population of postjunctional adrenoceptors is of the alpha 1 variety under normal in vitro experimental conditions, based on the potency order of selective agonists and on the effects of the antagonists prazosin and rauwolscine against responses to UK-14304. Angiotensin II (A II, 0.05 microM) however, without affecting resting baseline tension, markedly enhanced responses to UK-14304, particularly at low concentrations. This previously unseen component of the response to UK-14304 was resistant to prazosin (0.1 microM) but susceptible to rauwolscine (1 microM). A II would therefore appear to have a permissive role for the expression of a quiescent population of postjunctional alpha 2-adrenoceptors in the rabbit distal saphenous artery.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Angiotensina II/fisiologia , Quinoxalinas/farmacologia , Receptores Adrenérgicos alfa/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Artérias/efeitos dos fármacos , Tartarato de Brimonidina , Interações Medicamentosas , Técnicas In Vitro , Masculino , Prazosina/farmacologia , Coelhos , Ioimbina/farmacologiaRESUMO
1. Under normal experimental conditions, the rabbit isolated distal saphenous artery appears to contain a homogeneous population of postjunctional alpha 1-adrenoceptors. Prazosin competitively antagonized responses to noradrenaline (NA) with a pA2 value of 8.6, while a relatively high concentration of rauwolscine (1 microM), produced only a 2 fold rightward displacement of the NA cumulative concentration-response curve (CCRC). 2. Despite the fact that angiotensin II (AII) was without effect on responses to NA or phenylephrine in this preparation, this peptide made responses to NA less susceptible to the antagonistic action of prazosin. This was particularly evident on the lower portion of the CCRC for NA. These results suggest that in the presence of AII, NA produces contractile responses by an action mediated through a prazosin-resistant adrenoceptor. 3. An attempt was made to isolate a homogeneous population of postjunctional alpha 2-adrenoceptors by use of a receptor protection procedure involving the combination of rauwolscine and phenoxybenzamine. After the protection protocol no responses were observed to the alpha-adrenoceptor agonists NA, phenylephrine or UK-14304. In the presence of angiotensin II however, concentration-dependent contractions were observed to each of these agonists. Under these conditions the rank order of potency, UK-14304 greater than NA greater than phenylephrine, is consistent with that of an effect mediated through postjunctional alpha 2-adrenoceptors. 4. The responses to NA, after the protection protocol, in the presence of AII, were susceptible to the selective alpha 2-adrenoceptor antagonist, rauwolscine (1 microM), but resistant to the selective alpha 2-adrenoceptor antagonist prazosin (0.1 microM). Furthermore, the combination of rauwolscine (1 microM) and prazosin (0.1 I microM) was no more effective in blocking responses to NA than was rauwolscine (1 microM) alone. These results are consistent with the presence of a homogeneous population of postjunctional alpha 2-adrenoceptors. 5. Inducing a small degree of tone with a low concentration of the selective alpha 1-adrenoceptor agonist, phenylephrine, markedly increased the threshold sensitivity to the selective alpha 2-adrenoceptor agonist UK- 14304, in a manner analogous to that seen with All. 6. The results in the present study indicate that responses mediated via postjunctional alpha 2-adrenoceptors in the rabbit isolated distal saphenous artery are dependent upon a degree of vascular smooth muscle stimulation by some other receptor system. It is hypothesized that under normal experimental conditions, this function is fulfilled by stimulation of alpha l-adrenoceptors, while after alpha 1-adrenoceptor blockade the necessary positive influence can be provided by stimulation of All receptors. The implications for such an interaction between postjunctional alpha-adrenoceptor subtypes in demonstrating prazosin-resistant, rauwolscine- or yohimbine-sensitive responses in isolated blood vessels is discussed.
Assuntos
Músculo Liso Vascular/metabolismo , Norepinefrina/farmacologia , Prazosina/farmacologia , Receptores Adrenérgicos alfa/fisiologia , Antagonistas Adrenérgicos alfa/farmacologia , Angiotensina II/farmacologia , Animais , Tartarato de Brimonidina , Feminino , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Fenilefrina/farmacologia , Quinoxalinas/farmacologia , Coelhos , Receptores Adrenérgicos alfa/efeitos dos fármacos , Ioimbina/farmacologiaRESUMO
1. Characteristic features of noradrenaline (NA) and adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves in rat small mesenteric arteries in vitro have been investigated on an impulse-by-impulse basis. NA release was measured using continuous amperometry and ATP release was monitored by intracellular recording of excitatory junction potentials (e.j.ps). 2. Electrical stimuli evoked transient increases in oxidation current. During trains of ten stimuli at 0.5 - 4 Hz there was a depression in the amplitude of oxidation currents evoked following the first stimulus in the train. 3. The neuronal NA uptake inhibitor, desmethylimipramine (1 microM), increased the amplitude of the summed oxidation current evoked by ten stimuli at 1 Hz and slowed the decay of oxidation currents evoked by trains of ten stimuli at 1 and 10 Hz. 4. The alpha2-adrenoceptor antagonist, idazoxan (1 microM), increased the amplitudes of the oxidation currents evoked during trains of ten stimuli at 0.5 - 10 Hz but had no effect on the oxidation currents evoked by the first stimulus in the train. 5. Idazoxan (1 microM) increased the amplitude of all e.j.ps evoked during trains of stimuli at 0.5 and 1 Hz. In addition, the facilitatory effect of idazoxan on e.j.ps was significantly greater than that on oxidation currents. 6. The findings indicate that NA release from sympathetic nerves supplying small mesenteric arteries is regulated by activation of presynaptic alpha2-adrenoceptors and that clearance of released NA in this tissue depends, in part, upon neuronal uptake. The different effects of idazoxan on the oxidation currents and e.j.ps may indicate that the release of NA and ATP is differentially modulated.
Assuntos
Artérias Mesentéricas/inervação , Norepinefrina/metabolismo , Sistema Nervoso Simpático/metabolismo , Trifosfato de Adenosina/metabolismo , Inibidores da Captação Adrenérgica/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2 , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Cádmio/farmacologia , Corticosterona/farmacologia , Desipramina/farmacologia , Condutividade Elétrica , Estimulação Elétrica , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Idazoxano/farmacologia , Técnicas In Vitro , Cinética , Potenciais da Membrana/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa 2/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Tetrodotoxina/farmacologiaRESUMO
1. The effects of angiotensin II (AII) and Bay K 8644 on responses to noradrenaline (NA) mediated via postjunctional alpha 1- and/or alpha 2-adrenoceptors have been compared in three isolated venous preparations from the rabbit, the lateral saphenous vein, the left renal vein and the ear vein. 2. A similar action of AII and Bay K 8644 was observed only in the lateral saphenous vein; each potentiated responses to NA after isolation of a homogeneous population of postjunctional alpha 2- adrenoceptors. However, even in this preparation the mechanism of action for these agents was not identical. The sensitivity of KCl-induced contraction to changes in extracellular calcium ions (reflecting activation of voltage-dependent Ca2+ channels) was enhanced by Bay K 8644 but reduced by AII. 3. All produced a selective facilitation of responses mediated via postjunctional alpha 2-adrenoceptors. In the lateral saphenous vein it reduced the effectiveness of prazosin and facilitated responses after isolation of alpha 2-adrenoceptors with phenoxybenzamine and rauwolscine. It directly enhanced responses to NA in the ear vein, where only alpha 2-adrenoceptors are involved. In contrast, AII did not influence responses mediated via postjunctional alpha 1-adrenoceptors in the left renal vein (even after the receptor reserve had been removed with phenoxybenzamine) nor the 'rauwolscine-resistant' component of responses to NA in the saphenous vein. 4. Bay K 8644 enhanced contractile responses to NA mediated both via alpha 2-adrenoceptors, in the lateral saphenous vein, and via alpha 1-adrenoceptors in the left renal vein. Thus, unlike angiotensin II, no preferential effect was apparent. 5. Bay K 8644 was inactive against responses to NA in the rabbit isolated ear vein. Since the sustained component of responses to NA in this preparation is dependent upon the influx of extracellular Ca2 , these observations suggest that the influx of Ca2+ stimulated by NA is mediated via receptor-operated (1,4-dihydropyridine-resistant) Ca2 + channels.
Assuntos
Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Angiotensina II/farmacologia , Músculo Liso Vascular/fisiologia , Norepinefrina/fisiologia , Receptores Adrenérgicos alfa/fisiologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Cálcio/farmacologia , Orelha/irrigação sanguínea , Feminino , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Prazosina/farmacologia , Coelhos , Receptores Adrenérgicos alfa/efeitos dos fármacos , Receptores Adrenérgicos alfa/isolamento & purificação , Fluxo Sanguíneo Regional/efeitos dos fármacos , Veia Safena/efeitos dos fármacos , Ioimbina/farmacologiaRESUMO
1. The effects of the dihydropyridine calcium channel blocker, nifedipine, on noradrenaline-induced contractile responses have been examined in several isolated blood vessels from the rabbit, with particular emphasis on responses mediated via postjunctional alpha 2-adrenoceptors. 2. In the isolated renal vein, ear vein, distal saphenous artery, saphenous vein and plantaris vein, 0.1 microM and 1 microM nifedipine reduced responses elicited by 54 mM KCl by more than 70%. The remaining responses were abolished by alpha-adrenoceptor blockade, suggesting the involvement of noradrenaline released from neurones activating a dihydropyridine-resistant mechanism. 3. In the renal vein (alpha 1-), ear vein (predominantly alpha 2-), distal saphenous artery (alpha 1- greater than alpha 2-), saphenous vein and plantaris vein (alpha 2- greater than alpha 1-), 0.01 microM and 0.1 microM nifedipine produced concentration-related reductions in the maximum response to noradrenaline. However, 1 microM nifedipine was no more effective than 0.1 microM nifedipine and the reduction in the maximum varied from 10-25% of the control response. Thus, a sizeable component of the alpha-adrenoceptor-mediated response in all blood vessels is resistant to dihydropyridine calcium channel blockers and this appears to be unrelated to the alpha-adrenoceptor subtype involved. 4. Following irreversible inactivation of alpha 1-adrenoceptors and isolation of functional alpha 2-adrenoceptors in the saphenous vein, plantaris vein and distal saphenous artery (the latter requiring the presence of angiotensin II), the effect of nifedipine on responses to noradrenaline was increased. However, a component of the alpha 2-adrenoceptor response in each preparation was present even after the concentration of nifedipine was increased to 1 microM. 5. In the saphenous vein, a preparation in which it has been demonstrated previously that alpha 2-adrenoceptor-mediated responses are highly dependent upon the presence of extracellular calcium ions, partial depolarization with 20mM KCl failed to increase the inhibitory effect of 0.1 microM nifedipine. This suggests the involvement of dihydropyridine-resistant Ca2+ channels. The possible relationship between these dihydropyridine-resistant Ca2+ channels, alpha-adrenoceptor subtypes and 'receptor-operated' Ca2 + channels is discussed.
Assuntos
Músculo Liso Vascular/efeitos dos fármacos , Nifedipino/farmacologia , Receptores Adrenérgicos alfa/fisiologia , Animais , Feminino , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Coelhos , Receptores Adrenérgicos alfa/efeitos dos fármacosRESUMO
1. The roles of intracellular and extracellular-derived Ca2+ in alpha-adrenoceptor-mediated contractions to noradrenaline (NA) have been investigated in several isolated blood vessels from the rabbit by examining responses in the presence of a modified Krebs-Henseleit saline with 2.5 mM Ca2+ and a Ca2(+)-buffered saline with 0.1 microM free Ca2+. 2. NA was tested in preparations of the abdominal aorta, distal saphenous artery, renal vein, lateral saphenous vein, plantaris vein and ear vein exposed to a Ca2(+)-buffered saline with 0.1 microM [Ca2+]. A concentration of NA which was maximally effective in modified Krebs-Henseleit saline, produced an initial transient contraction (ITC) followed by a relaxation towards baseline. This is evidence that alpha-adrenoceptor-mediated responses in all these blood vessels depend upon calcium from both sources. 3. The ITC was particularly pronounced in the arteries and was associated more closely with the alpha 1-receptor subtype. In the abdominal aorta, distal saphenous artery and renal vein the ITC can almost exclusively be attributed to an alpha 1-adrenoceptor (prazosin-sensitive, rauwolscine-resistant). In the ear vein, and to a lesser extent the plantaris vein, the ITC was mediated in part by an alpha 2-adrenoceptor (prazosin-resistant, rauwolscine-sensitive). 4. alpha 2-Adrenoceptors in the lateral saphenous vein largely account for the response to NA in modified Krebs-Henseleit saline, but alpha 1-adrenoceptors mediate the ITC in Ca2(+)-buffered saline. After selective inactivation of alpha 1-adrenoceptors with a combination of phenoxybenzamine and rauwolscine, responses to NA in modified Krebs-Henseleit saline are slow in onset and there is no ITC in Ca2(+)-buffered saline. 5. The possible significance of the coupling of postjunctional alpha 2-adrenoceptors to dual sources of Ca2 + is discussed in relation to the interaction between alpha-adrenoceptor subtypes and the ease of demonstrating functional alpha 2-adrenoceptors in isolated blood vessels.
Assuntos
Cálcio/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Receptores Adrenérgicos alfa/fisiologia , Animais , Feminino , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Norepinefrina/farmacologia , Fenoxibenzamina/farmacologia , Cloreto de Potássio/farmacologia , Prazosina/farmacologia , Coelhos , Receptores Adrenérgicos alfa/efeitos dos fármacos , Veia Safena/efeitos dos fármacos , Veias/efeitos dos fármacos , Ioimbina/farmacologiaRESUMO
1. An attempt has been made, with the irreversible alpha-adrenoceptor antagonist phenoxybenzamine, to find the conditions under which postjunctional alpha 1-adrenoceptors in the rabbit isolated saphenous vein can be inactivated, such that postjunctional alpha 2-adrenoceptors can be studied in isolation. 2. Following exposure to various concentrations of phenoxybenzamine, no evidence was found for a selective inactivation of the postjunctional population of alpha 1-adrenoceptors: the "rauwolscine-resistant' (alpha 1-) and the "rauwolscine-sensitive' (alpha 2-) responses to (--)-noradrenaline were similarly affected. 3. However, in "receptor protection' experiments following exposure to a combination of phenoxybenzamine and the selective alpha 2-adrenoceptor antagonist rauwolscine, the remaining response to (--)-noradrenaline appeared to be mediated by a single population of postjunctional alpha 2-adrenoceptors: the response was insensitive to prazosin and rauwolscine was more potent than corynanthine. 4. Partial isolation of the alpha 1-adrenoceptor population was attempted by pre-exposure of the preparation to a combination of phenoxybenzamine and a selective alpha 1-adrenoceptor antagonist, i.e. prazosin or YM-12617. Following receptor protection, the inhibition produced by "selective' concentrations of either of these alpha 1-adrenoceptor antagonists were not significantly different from that observed in control preparations (no phenoxybenzamine). However, the selective alpha 2-adrenoceptor antagonists rauwolscine and CH-38083 were still able to inhibit part of the remaining responses to NA. This is interpreted as indicating that, in addition to protecting the putative postjunctional alpha 1-adrenoceptors, these procedures fail to produce complete inactivation of postjunctional alpha 2-adrenoceptors. 5. It is concluded that, although phenoxybenzamine appeared to be non-selective for the two populations of postjunctional alpha-adrenoceptors in the rabbit isolated saphenous vein, inclusion of a "selective' concentration of a competitive antagonist during the inactivation period results in differing degrees of functional protection of each subtype. Pharmacological isolation was possible for alpha 2-adrenoceptors but not convincingly for alpha 1-adrenoceptors.