RESUMO
It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively low efficacy has been established, whereas downstream BK currents seem to be increased. Thus, the overall performance of this signaling pathway in SHR is elusive. For a better understanding, we focused on one aspect, the direct targeting of the BK channel by the G-protein/AC pathway and tested the hypothesis that the comparatively low AC pathway efficacy in SHR results in a reduced agonist-induced stimulation of BK currents. This hypothesis was investigated using freshly isolated smooth muscle cells from WKY and SHR rat tail artery and the patch-clamp technique. It was observed that: (1) single BK channels have similar current-voltage relationships, voltage-dependence and calcium sensitivity; (2) BK currents in cells with a strong buffering of the BK channel activator calcium have similar current-voltage relationships; (3) the iloprost-induced concentration-dependent increase of the BK current is larger in WKY compared to SHR; (4) the effects of activators of the PKA pathway, the catalytic subunit of PKA and the potent and selective cAMP-analogue Sp-5,6-DCl-cBIMPS on BK currents are similar. Thus, our data suggest that the lower iloprost-induced stimulation of the BK current in freshly isolated rat tail artery smooth muscle cells from SHR compared with WKY is due to the lower efficacy of upstream elements of the G-Protein/AC/BK channel pathway.
Assuntos
Cálcio , Hipertensão , Iloprosta , Canais de Potássio Ativados por Cálcio de Condutância Alta , Músculo Liso Vascular , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vasodilatadores , Animais , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Ratos , Cálcio/metabolismo , Iloprosta/farmacologia , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Vasodilatadores/farmacologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Masculino , Artérias/efeitos dos fármacos , Artérias/metabolismo , Cauda/irrigação sanguínea , Transdução de Sinais/efeitos dos fármacosRESUMO
The signals that regulate peripheral blood vessel formation during development are still under investigation. The hormone leptin promotes blood vessel formation, adipose tissue establishment and expansion, tumor growth, and wound healing, but the underlying mechanisms for these actions are currently unknown. We investigated whether leptin promotes angiogenesis in the developing tail fin using embryonic transgenic xflk-1:GFP Xenopus laevis, which express a green fluorescent protein on vascular endothelial cells to mark blood vessels. We found that leptin protein is expressed in endothelial cells of developing blood vessels and that leptin treatment via injection increased phosphorylated STAT3 signaling, which is indicative of leptin activation of its receptor, in blood vessels of the larval tail fin. Leptin administration via media increased vessel length, branching, and reconnection with the cardinal vein, while decreased leptin signaling via immunoneutralization had an opposing effect on vessel development. We also observed disorganization of major vessels and microvessels of the tail fin and muscle when leptin signaling was decreased. Reduced leptin signaling lowered mRNA expression of cenpk, gpx1, and mmp9, markers for cell proliferation, antioxidation, and extracellular matrix remodeling/cell migration, respectively, in the developing tail, providing insight into three possible mechanisms underlying leptin's promotion of angiogenesis. Together these results illustrate that leptin levels are correlated with embryonic angiogenesis and that leptin coordinates multiple aspects of blood vessel growth and development, showing that leptin is an important morphogen during embryonic development.
Assuntos
Larva , Leptina , Neovascularização Fisiológica , Transdução de Sinais , Cauda , Xenopus laevis , Animais , Leptina/metabolismo , Cauda/irrigação sanguínea , Cauda/embriologia , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Larva/metabolismo , Vasos Sanguíneos/embriologia , Vasos Sanguíneos/metabolismo , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/genética , Animais Geneticamente Modificados , Fator de Transcrição STAT3/metabolismo , Embrião não Mamífero/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
As artérias mesentéricas das aves são importantes para a irrigação do aparelho digestório e encontram-se associadas ao ganho de peso e conversão alimentar. Objetivou-se descrever as origens, esqueletopias, medidas e principais ramificações das artérias mesentéricas cranial e caudal em avestruzes. Foram utilizados 41 cadáveres de filhotes de avestruzes, 23 machos e 18 fêmeas, obtidos de um criadouro após morte natural. Os cadáveres foram fixados com formaldeído a 10% e tiveram o sistema vascular preenchido com Petrolatex® S-65 colorido. As artérias mesentéricas, cranial e caudal e seus ramos proximais foram dissecados "in situ" e medidas com paquímetro digital. A artéria mesentérica cranial teve comprimento médio de 3,68 ± 1,04 cm e surgiu da aorta descendente ao nível da oitava vértebra torácica na maioria dos casos. Ramificou-se em artérias jejunal e ileocecal. A artéria jejunal ofereceu média de 14,04 ±2,08 ramos ao jejuno e a artéria ileocecal originou um ramo retal e outro que se bifurcou para derivar ramos para íleo, ceco e reto. Em um espécime macho a artéria ileocecal foi ramo da artéria celíaca. A artéria mesentérica caudal originou-se na porção terminal da aorta descendente predominantemente ao nível das 4ª e 6ª vértebras sacro-caudais. Perto da extremidade caudal do rim emitiu os ramos cranial e caudal. O primeiro irrigou o reto e anastomosou-se com ramo retal da artéria mesentérica cranial; o segundo irrigou a porção final do reto, cloaca e bolsa cloacal. Não houve diferença significativa (p<0,05) entre as medidas, esqueletopia e número de ramificações das artérias entre os sexos.(AU)
The mesenteric arteries of birds are important for the irrigation of the digestive tract and are associated with weight gain and food conversion. This study aimed to describe the origins, skeletopy, measures and main branches of cranial and caudal mesenteric arteries in ostriches. Forty-one cadavers of ostrich chicks, 23 males and 18 females, obtained from a farmer after natural death. The cadavers were fixed with 10% formaldehyde solution and their vascular system was filled with colored Petrolatex® S-65. The cranial and caudal mesenteric arteries and its proximal branches were dissected in situ and measured with a digital caliper. The mesenteric artery had an average length of 3.68cm±1.04 and emerged from the descending aorta at the level of the eighth thoracic vertebra in most cases; it branched into jejunal and ileocecal arteries. The jejunal artery sent a mean of 14 (14.04±2.08) branches to the jejunum. The ileocecal artery sent a rectal branch and another branch that irrigated ileum, cecum and rectum. In a male specimen the ileocecal artery was originated from the celiac artery. The caudal mesenteric artery emerged in the terminal portion of the descending aorta predominantly at the level of the 4th and 6th sacrocaudal vertebrae. Near the caudal end of the kidney it issued the cranial and caudal branches. The first irrigated the rectum and anastomosed with the rectal branch of the cranial mesenteric artery; the second irrigated the final part of the rectum, cloaca and cloacal bursa. There was no significant difference (p<0.05) between measurements, skeletopy and number of branches of the arteries between genders.(AU)
Assuntos
Animais , Intestinos/irrigação sanguínea , Artérias Mesentéricas/anatomia & histologia , Crânio/irrigação sanguínea , Struthioniformes/anatomia & histologia , Cauda/irrigação sanguínea , Sistema Cardiovascular/anatomia & histologiaRESUMO
This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7 percent), WSS (Wistar/E+: 36; SHR/E+: 40 percent) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.
Assuntos
Animais , Masculino , Ratos , Hipertensão/fisiopatologia , Polietilenoglicóis/farmacologia , Cauda/irrigação sanguínea , Resistência Vascular/efeitos dos fármacos , Artérias/efeitos dos fármacos , Artérias/fisiologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Viscosidade Sanguínea/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Modelos Animais , Ratos Endogâmicos SHR , Ratos Wistar , Resistência Vascular/fisiologiaRESUMO
OBJETIVO: Estudar dois modelos de obesidade, exócrina e endócrina, e sua associação sobre a pressão arterial de cauda (PAC), o peso corporal (PC), o metabolismo glicídico (ISI) e gordura epididimal relativa (GER). MÉTODOS: Foram estudados ratos machos da cepa Wistar. O grupo MSG recebeu glutamato monossódico no período neonatal. Aos 3 meses de idade parte desses animais passou a receber dieta cafeteria (CAF). Os animais receberam controle salina no período neonatal. Durante 12 semanas foram pesados (PC) e tiveram a pressão arterial de cauda (PAC) aferida. O Teste de Tolerância Oral à Glicose foi realizado e o Índice de Sensibilidade à Insulina (ISI), calculado. O peso ventricular relativo (PVR) e a gordura epididimal relativa (GER) também foram calculados. RESULTADOS: Não se verificou alterações no PC e na PAC. A obesidade induzida pela administração de MSG e CAF, isoladamente, promoveu aumento da resistência à insulina (WST = 23,25 ± 9,31; CAF = 15,92 ± 9,10*; MSG = 13,41 ± 3,84* mg-1mU-1, p < 0,05 vs WST) e da gordura visceral (WST = 6,20 ± 0,57; CAF = 8,27 ± 1,53*; MSG = 8,23 ± 1,98* g/100 g, *p < 0,05), quando esses animais foram comparados com os controles. A associação de ambos os modelos de obesidade produziu um efeito sinérgico sobre a resistência à insulina (MSG+CAF = 9,34 ± 5,77 mg-1mU-1, p<0,05 vs MSG e CAF) e sobre o conteúdo de gordura visceral (MSG+CAF = 11,12 ± 3,85 g/100g, p < 0,05 vs MSG e CAF). CONCLUSÃO : A associação de dois modelos de obesidade agrava a resistência à insulina e esse fato pode ser atribuído pelo menos em parte ao aumento da GER.
OBJECTIVE: To study two different models of obesity, exocrine and endocrine, and its association on tail arterial pressure (TAP), body weight (BW), glucose metabolism and visceral fat content. METHODS: Male Wistar rats were studied. The MSG group was composed by rats that received of MSG in neonatal period. At the 3rd month of life, part of these animals received cafeteria diet. Animals received saline control in the neonatal period. In the 12 weeks of study, body weight and blood pressure were measured twice a week. In the end of this period on, Oral Glucose Tolerance Test (OGTT) was performed and the Insulin Sensitivity Index (ISI) was calculated, also the left Relative Ventricular Weight (RLW) and Relative Epididimal Fat Weight (REFW) were obtained. RESULTS: No changes on BW and TAP were verified. The obesity induced by MSG and CAF, individually, let to increases on insulin resistance (WST = 23,25 ± 9,31; CAF = 15,92 ± 9,10*; MSG = 13,41 ± 3,84* mg-1mU-1, p < 0,05 vs WST) and relative epididimal fat content (WST = 6,20 ± 0,57; CAF = 8,27 ± 1,53*; MSG = 8,23 ± 1,98* g/100 g, *p < 0,05) when these rats were compared to control rats. An enhanced effect upon these parameters was observed with the association of both obesity models (MSG+CAF = 9,34 ± 5,77 mg-1mU-1, p < 0,05 vs MSG and CAF) and visceral fat content (MSG+CAF = 11,12 ± 3,85 g/100g, p < 0,05 vs MSG and CAF). CONCLUSION: The association of these two experimental models of obesity aggravates insulin resistance that probably is due at least in part to the increase of visceral fat content.
Assuntos
Animais , Masculino , Ratos , Pressão Sanguínea , Glucose/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Cauda/irrigação sanguínea , Glândulas Exócrinas , Sistemas Neurossecretores , Obesidade/etiologia , Ratos WistarRESUMO
Chronic lead exposure induces hypertension in humans and animals, affecting endothelial function. However, studies concerning acute cardiovascular effects are lacking. We investigated the effects of acute administration of a high concentration of lead acetate (100 µÌ) on the pressor response to phenylephrine (PHE) in the tail vascular bed of male Wistar rats. Animals were anesthetized with sodium pentobarbital and heparinized. The tail artery was dissected and cannulated for drug infusion and mean perfusion pressure measurements. Endothelium and vascular smooth muscle relaxation were tested with acetylcholine (5 µg/100 µL) and sodium nitroprusside (0.1 µg/100 µL), respectively, in arteries precontracted with 0.1 µM PHE. Concentration-response curves to PHE (0.001-300 µg/100 µL) were constructed before and after perfusion for 1 h with 100 µÌ lead acetate. In the presence of endothelium (E+), lead acetate increased maximal response (Emax) (control: 364.4 ± 36, Pb2+: 480.0 ± 27 mmHg; P < 0.05) and the sensitivity (pD2; control: 1.98 ± 0.07, 2.38 ± 0.14 log mM) to PHE. In the absence of endothelium (E-) lead had no effect but increased baseline perfusion pressure (E+: 79.5 ± 2.4, E-: 118 ± 2.2 mmHg; P < 0.05). To investigate the underlying mechanisms, this protocol was repeated after treatment with 100 µM L-NAME, 10 µM indomethacin and 1 µM tempol in the presence of lead. Lead actions on Emax and pD2 were abolished in the presence of indomethacin, and partially abolished with L-NAME and tempol. Results suggest that acute lead administration affects the endothelium, releasing cyclooxygenase-derived vasoconstrictors and involving reactive oxygen species.
Assuntos
Animais , Masculino , Ratos , Endotélio Vascular/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Cauda/irrigação sanguínea , Vasoconstrição/efeitos dos fármacos , Endotélio Vascular/fisiologia , Compostos Organometálicos/administração & dosagem , Fenilefrina/farmacologia , Ratos WistarRESUMO
The investigation of resistance vessels is generally costly and difficult to execute. The present study investigated the diameters and the vascular reactivity of different segments of the rat tail artery (base, middle, and tail end) of 30 male Wister rats (EPM strain) to characterize a conductance or resistance vessel, using a low-cost simple technique. The diameters (mean ± SEM) of the base and middle segments were 471 ± 4.97 and 540 ± 8.39 µm, respectively, the tail end was 253 ± 2.58 µm. To test reactivity, the whole tail arteries or segments were perfused under constant flow and the reactivity to phenylephrine (PHE; 0.01-300 µg) was evaluated before and after removal of the endothelium or drug administration. The maximal response (Emax) and sensitivity (pED50) to PHE of the whole tail and the base segment increased after endothelium removal or treatment with 100 µM L-NAME, which suggests modulation by nitric oxide. Indomethacin (10 µM) and tetraethylammonium (5 mM) did not change the Emax or pED50 of these segments. PHE and L-NAME increased the pED50 of the middle and the tail end only and indomethacin did not change pED50 or Emax. Tetraethylammonium increased the sensitivity only at the tail end, which suggests a blockade of vasodilator release. Results indicate that the proximal segment of the tail artery possesses a diameter compatible with a conductance vessel, while the tail end has the diameter of a resistance vessel. In addition, the vascular reactivity to PHE in the proximal segment is nitric oxide-dependent, while the tail end is dependent on endothelium-derived hyperpolarizing factor.
Assuntos
Animais , Masculino , Ratos , Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiologia , Cauda/irrigação sanguínea , Resistência Vascular/fisiologia , Artérias/anatomia & histologia , Artérias/efeitos dos fármacos , Artérias/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Modelos Animais , Fenilefrina/farmacologia , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Resistência Vascular/efeitos dos fármacos , Vasoconstritores/farmacologiaRESUMO
The delivery of transgenes to the central nervous system (CNS) can be a valuable tool to treat CNS diseases. Various systems for the delivery to the CNS have been developed; vascular delivery of viral vectors being most recent. Here, we investigated gene transfer to the CNS by intravenous injection of recombinant adenoviral vectors, containing green fluorescence protein (GFP) as a reporter gene. Expression of GFP was first observed 6 days after the gene transfer, peaked at 14 days, and almost diminished after 28 days. The observed expression of GFP in the CNS was highly localized to hippocampal CA regions of cerebral neocortex, inferior colliculus of midbrain, and granular cell and Purkinje cell layers of cerebellum. It is concluded that intravenous delivery of adenoviral vectors can be used for gene delivery to the CNS, and hence the technique could be beneficial to gene therapy.
Assuntos
Animais , Feminino , Camundongos , Adenovírus Humanos/isolamento & purificação , Barreira Hematoencefálica , Encéfalo/virologia , Cerebelo/citologia , Cerebelo/virologia , Estudo Comparativo , Genes Reporter , Vetores Genéticos/administração & dosagem , Vetores Genéticos/isolamento & purificação , Vetores Genéticos/farmacocinética , Hipocampo/virologia , Colículos Inferiores/virologia , Injeções Intravenosas , Proteínas Luminescentes/análise , Proteínas Luminescentes/biossíntese , Proteínas Luminescentes/genética , Camundongos Endogâmicos BALB C , Neuroglia/virologia , Neurônios/virologia , Células de Purkinje/virologia , Células Piramidais/virologia , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Cauda/irrigação sanguínea , Distribuição TecidualRESUMO
The aim of the investigation was to examine the effects of cooling on the tail artery regarding the scarceness of such studies in spite of the essential thermoregulatory role played by this vessel. Segments of the proximal portion were suspended isometrically in medium containig 1.25 mM Ca. Lowering the temperature to 25 degrees Celsius increased the sensitivity and maximum strength of the adrenaline concentration-effect curves. These changes were reversed by warming to 37 degrees Celsius. Cocaine attenuated the increase of sensitivity without changing the increase of the maximum response. Either the sensitivity and strength of the responses to phenylephrine and serotomin were increased by cooling. Clonidine evoked weak contractions in 18 out of 38 experiments. After cooling, the responses persisted only in 7 arteries and the strength was almost halved. Responses to field eletric stimulation at 25 degrees Celsius exhibited a pronounced increase of strength and a small increase of sensitivity. -log Kb for prazosin against adrenaline was encreased by cooling (8.7 and 9.1 at 37 degrees Celsius and 25 degrees Celsius C, P<0.01). After partial receptor inactivation using phenoxybenzamine, the dissociation-constant (KA) indicated a moderate affinity for phenylephrine that was not changed by cooling (4.1 and 4.2 x 10(-6) at 37 degrees Celsius respectively). Receptor reserve and occupancy at EC(50) also remained unchanged at 25 degrees Celsius. It can be concluded that: 1) cooling increases the tail artery reactivity, partly as a consequence of the inhibition of adrenergic neuronal uptake; 2) responsiveness to alpha 2-agonists is not in volved in the effects of cooling whereas the role of alpha 1-adrenoceptor could not be properly clarified; 3) cooling may facilitate some steps of the contractile activation beyond the agonist-receptor interaction.
Assuntos
Animais , Ratos , Agonistas alfa-Adrenérgicos/farmacologia , Artérias/fisiologia , Temperatura Baixa , Sequestradores de Radicais Livres/farmacologia , Serotonina/farmacologia , Cauda/irrigação sanguínea , Artérias/efeitos dos fármacos , Clonidina/farmacologia , Estimulação Elétrica , Epinefrina/farmacologia , Fenoxibenzamina/farmacologia , Fenilefrina/farmacologia , Prazosina/farmacologiaRESUMO
The aim of the investigation was to examine the effects of cooling on the tail artery regarding the scarceness of such studies in spite of the essential thermoregulatory role played by this vessel. Segments of the proximal portion were suspended isometrically in medium containig 1.25 mM Ca. Lowering the temperature to 25 degrees Celsius increased the sensitivity and maximum strength of the adrenaline concentration-effect curves. These changes were reversed by warming to 37 degrees Celsius. Cocaine attenuated the increase of sensitivity without changing the increase of the maximum response. Either the sensitivity and strength of the responses to phenylephrine and serotomin were increased by cooling. Clonidine evoked weak contractions in 18 out of 38 experiments. After cooling, the responses persisted only in 7 arteries and the strength was almost halved. Responses to field eletric stimulation at 25 degrees Celsius exhibited a pronounced increase of strength and a small increase of sensitivity. -log Kb for prazosin against adrenaline was encreased by cooling (8.7 and 9.1 at 37 degrees Celsius and 25 degrees Celsius C, P<0.01). After partial receptor inactivation using phenoxybenzamine, the dissociation-constant (KA) indicated a moderate affinity for phenylephrine that was not changed by cooling (4.1 and 4.2 x 10(-6) at 37 degrees Celsius respectively). Receptor reserve and occupancy at EC(50) also remained unchanged at 25 degrees Celsius. It can be concluded that: 1) cooling increases the tail artery reactivity, partly as a consequence of the inhibition of adrenergic neuronal uptake; 2) responsiveness to alpha 2-agonists is not in volved in the effects of cooling whereas the role of alpha 1-adrenoceptor could not be properly clarified; 3) cooling may facilitate some steps of the contractile activation beyond the agonist-receptor interaction. (AU)
Assuntos
Animais , Ratos , Temperatura Baixa , Cauda/irrigação sanguínea , Artérias/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Serotonina/farmacologia , Sequestradores de Radicais Livres/farmacologia , Artérias/efeitos dos fármacos , Fenilefrina/farmacologia , Epinefrina/farmacologia , Clonidina/farmacologia , Prazosina/farmacologia , Fenoxibenzamina/farmacologia , Estimulação ElétricaRESUMO
Se estudiaron los efectos de la Rianodina (RI) y cafeína (CF) sobre las contracciones inducidas por noradrenalina (NA) en arterias de la cola de ratas espontáneamente hipertensas (SHR) y normotensas (WKY). El depósito intracellular de calcio sensible a NA fue vaciado completamente por exposición a NA 1 AM en solución libre de calcio, y fue responsable de un 40% de la contracción a NA en presencia de calcio 1.6 mM. Sin embargo, solamente en 60% del depósito fue utilizado para la contracción en calcio 1.6 mM. La reexposición al calcio extracelular rellenó el depósito sensible a NA en menos de 10 minutos, pero mientras el depóstio de la WKY captó aproximadamente el mismo calcio que tenía previamente (a juzgar por la magnitud de la respuesta mecánica posterior en solución libre de calcio), la SHR captó aproximadamente el doble de calcio en las msmas condiciones. La RI impidió el relleno del depósito en la SHR y WKY, sin liberar calcio del depósito y sin afectar el influjo de calcio a través de la membrana. La CF también previno el relleno de los depósitos sensibles a NA, pero también liberó calcio del depósito y promovió el ingreso de calcio a través de la membrana celular. Se concluye que la principal acción de la RI em el músculo liso de la cola de la rata es prevenir la captación de calcio por el depósito intracelular sensible a NA, mientras que la CF tiene varios efectos: inhibición de la captación de calcio por el depósito, liberación de calcio por depóstio, y apertura de canales de calcio de la membrana celular. Además, en la SHR (pero no en la WKY) la pérdida de calcio de la membrana vuelve a ésta más permeable al calcio, permitiendo una captación aumentada de calcio por el depósito intracelular en una subsiguiente exposición al calcio extracelular (AU)
Assuntos
Ratos , Animais , Cálcio/metabolismo , Rianodina/farmacologia , Cafeína/farmacologia , Norepinefrina/farmacologia , Contração Muscular/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Artérias/metabolismo , Ratos Endogâmicos , Cauda/irrigação sanguínea , Ratos Endogâmicos WKYRESUMO
Se estudiaron los efectos de la Rianodina (RI) y cafeína (CF) sobre las contracciones inducidas por noradrenalina (NA) en arterias de la cola de ratas espontáneamente hipertensas (SHR) y normotensas (WKY). El depósito intracellular de calcio sensible a NA fue vaciado completamente por exposición a NA 1 µM en solución libre de calcio, y fue responsable de un 40% de la contracción a NA en presencia de calcio 1.6 mM. Sin embargo, solamente en 60% del depósito fue utilizado para la contracción en calcio 1.6 mM. La reexposición al calcio extracelular rellenó el depósito sensible a NA en menos de 10 minutos, pero mientras el depóstio de la WKY captó aproximadamente el mismo calcio que tenía previamente (a juzgar por la magnitud de la respuesta mecánica posterior en solución libre de calcio), la SHR captó aproximadamente el doble de calcio en las msmas condiciones. La RI impidió el relleno del depósito en la SHR y WKY, sin liberar calcio del depósito y sin afectar el influjo de calcio a través de la membrana. La CF también previno el relleno de los depósitos sensibles a NA, pero también liberó calcio del depósito y promovió el ingreso de calcio a través de la membrana celular. Se concluye que la principal acción de la RI em el músculo liso de la cola de la rata es prevenir la captación de calcio por el depósito intracelular sensible a NA, mientras que la CF tiene varios efectos: inhibición de la captación de calcio por el depósito, liberación de calcio por depóstio, y apertura de canales de calcio de la membrana celular. Además, en la SHR (pero no en la WKY) la pérdida de calcio de la membrana vuelve a ésta más permeable al calcio, permitiendo una captación aumentada de calcio por el depósito intracelular en una subsiguiente exposición al calcio extracelular