RESUMEN
The scaling relations for the dispersion coefficients of long-range interactions between the Mu(1s)-Mu(1s, 2s, or 2p) systems and the H(1s)-H(1s, 2s, or 2p) systems are obtained using analytical properties of hydrogenic wavefunctions, which allows us to obtain the dispersion coefficients for Mu(1s)-Mu(1s, 2s, or 2p) systems from the corresponding H(1s)-H(1s, 2s, or 2p) systems. Additionally, the dispersion coefficients of long-range interactions of Mu(1s) with the ground-state H, noble gas atoms He, Ne, Ar, Kr, and Xe, alkali-metal atoms Li, Na, K, and Rb, alkaline-earth atoms Be, Mg, Ca, and Sr, and Cu, Ag, F, and Cl atoms are calculated.
RESUMEN
INTRODUCTION: Purpose of the study is to evaluate a possible influence of subdural drainage duration and burr hole quantity on a relapse of a unilateral chronic subdural haematoma (CHSH). METHODS: Sixty - five patients who underwent evacuation of unilateral CHSH via 1 or 2 burr holes and subdural drainage during a period from January 2014 to December 2018 were retrospectively analyzed. Duration of the subdural drainage and the number of burr holes used were assessed in relation to an incidence of CHSH recurrence. According to the subdural drainage duration, we divided the patient cohort into two subgroups: with the subdural drainage duration of 1-3 days and 4-5 days. We also evaluated a possible influence of the subdural drainage duration on risk of postoperative infection. RESULTS: An overall incidence of CHSH recurrence was 18.5%. In 45 patients treated by means of a single burr hole the haematoma recurrence was observed in 10 patients (22.2%), in 22 patients with two burr holes recurrence occurred in 2 of them (9.1%). The difference was however, not statistically significant (p=0.3214). We did not observe any significant influence of age, gender and subdural drainage duration on the incidence of CHSH recurrence. The duration of subdural drainage had not significant impact on postoperative infection rate (p=0.0950). CONCLUSION: The number of burr holes used does not affect the rate of unilateral CHSH recurrence. Similarly the duration of subdural drainage affects neither the unilateral CHSH recurrence rate nor the incidence of postoperative infection.
Asunto(s)
Hematoma Subdural Crónico/cirugía , Drenaje , Humanos , Recurrencia , Estudios Retrospectivos , TrepanaciónRESUMEN
PURPOSE: Cage subsidence (CS) represents a risk factor for adjacent segment degeneration (ASD) and unfavorable results of anterior cervical discectomy (ACD). METHODS: Sixty-one patients after level 1 or 2 of ACD with implantation of Zero Profile VA cage were included in the study. CS was assessed with a follow-up period of 12 months after ACD. The impacts of factors such as sex, age, number of operated segments, osteoporosis and extent of peroperative distraction were assessed in relation to the incidence of CS. The influences of CS on clinical results (VAS, NDI, Odom's criteria) and ASD incidence were evaluated. RESULTS: In 74 % of cases there was the presence of CS into both adjacent vertebral bodies. CS into the ventral part of motion segment was dominant during the entire follow-up period. CS had no influence on clinical results of ACD. Parallel CS into both ventral and dorsal parts of motion segments significantly increased the incidence of proximal ASD (p = 0.0163). Osteoporosis and extent of peroperative distraction were linked to higher incidence of CS into the dorsal part of motion segment (p Ë 0.05). CONCLUSIONS: Osteoporosis and the extent of peroperative distraction are risk factors for the subsidence of anchored cage and while increasing the incidence of proximal adjacent segment degeneration it has no significant influence on clinical results of surgery (Tab. 3, Fig. 5, Ref. 32).
Asunto(s)
Vértebras Cervicales , Fusión Vertebral , Vértebras Cervicales/cirugía , Discectomía , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Dysphagia is a common finding after anterior cervical discectomy. The incidence and severity of swallowing disorders are variable and depend on many factors. METHODS: 73 patients after 1- or 2-level anterior cervical discectomy and fusion /ACDF/ were enrolled in prospective, single-center study. The severity of dysphagia was evaluated by the Bazaz-Yoo dysphagia score before surgery and 6 weeks, 3, 6 and 12 months after surgery. The impact of factors such as sex, age, number of operated segments, smoking, gastroesophageal reflux disease, hypertension, duration of surgery and pre-existing dysphagia on the incidence of dysphagia after surgery was verified. The correlation between the duration of surgery and severity of postoperative dysphagia, and similarly between the age and severity of preoperative and postoperative dysphagia was studied. RESULTS: Dysphagia was present in 22% patients within 12 months after surgery. No patient reported severe dysphagia. No significant relationship was demonstrated between sex, age, number of operated segments, pre-existing dysphagia, gastroesophageal reflux disease, hypertension and the incidence of dysphagia after surgery. Smokers showed a significantly lower incidence of dysphagia before surgery and within 12 months after ACDF (p.
Asunto(s)
Vértebras Cervicales , Trastornos de Deglución , Discectomía , Fusión Vertebral , Vértebras Cervicales/cirugía , Trastornos de Deglución/etiología , Discectomía/efectos adversos , Estudios de Seguimiento , Humanos , Estudios Prospectivos , Fusión Vertebral/efectos adversos , Resultado del TratamientoRESUMEN
Cell invasion from an aggregate into a surrounding extracellular matrix (ECM) is an important process during development disease, e.g., vascular network assembly or tumor progression. To describe the behavior emerging from autonomous cell motility, cell-cell adhesion and contact guidance by ECM filaments, we propose a suitably modified cellular Potts model. We consider an active cell motility process in which internal polarity is governed by a positive feedback from cell displacements, a mechanism that can result in highly persistent motion when constrained by an oriented ECM structure. The model allows us to explore the interplay between haptotaxis, matrix degradation and active cell movement. We show that for certain conditions the cells are able to both invade the ECM and follow the ECM tracks. Furthermore, we argue that enforcing mechanical equilibrium within a bulk cell mass is of key importance in multicellular simulations.
Asunto(s)
Neoplasias Encefálicas/patología , Adhesión Celular , Matriz Extracelular/fisiología , Modelos Biológicos , Animales , Neoplasias Encefálicas/ultraestructura , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Colágeno Tipo I/metabolismo , Células Endoteliales/citología , Humanos , Invasividad Neoplásica/patología , RatasRESUMEN
The projection method is used to demonstrate the existence of positron attachment to three doubly excited states of helium. The e(+)He(2s(2) (1)S(e))deg, e(+)He(3s(2) (1)S(e)), and the e(+)He(2s2p (3)P(o)) states have binding energies of 0.447, 0.256, and 0.486 eV, respectively. These energies were computed with the stochastic variational method and the configuration interaction method. These states will exist as resonances in the e(+)-He continuum, and the e(+)He(2s(2) (1)S(e)) state could be detectable in the e(+)+He collision spectrum. A resonance width of 0.068 eV was computed for the e(+)He(2s(2) (1)S(e)) state by using the complex rotation method. The existence of a series of e(+)He(ns(2) (1)S(e)) resonances associated with the He(ns(2)) double Rydberg series is also predicted, and an explicit calculation demonstrating the existence of the e(+)He(3s(2) (1)S(e)) state is reported.
RESUMEN
Advanced cirrhosis is associated with generalized vasodilation of unknown origin, which contributes to mortality. Cirrhotic patients are endotoxemic, and activation of vascular cannabinoid CB1 receptors has been implicated in endotoxin-induced hypotension. Here we show that rats with biliary cirrhosis have low blood pressure, which is elevated by the CB1 receptor antagonist SR141716A. The low blood pressure of rats with CCl4-induced cirrhosis was similarly reversed by SR141716A, which also reduced the elevated mesenteric blood flow and portal pressure. Monocytes from cirrhotic but not control patients or rats elicited SR141716A-sensitive hypotension in normal recipient rats and showed significantly elevated levels of anandamide. Compared with non-cirrhotic controls, in cirrhotic human livers there was a three-fold increase in CB1 receptors on isolated vascular endothelial cells. These results implicate anandamide and vascular CB1 receptors in the vasodilated state in advanced cirrhosis and indicate a novel approach for its management.
Asunto(s)
Ácidos Araquidónicos/metabolismo , Cirrosis Hepática/fisiopatología , Receptores de Droga/metabolismo , Vasodilatación/fisiología , Animales , Moduladores de Receptores de Cannabinoides , Cromatografía Líquida de Alta Presión , Endocannabinoides , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Hipotensión/etiología , Masculino , Espectrometría de Masas , Monocitos/metabolismo , Alcamidas Poliinsaturadas , Ratas , Ratas Sprague-Dawley , Receptores de CannabinoidesRESUMEN
We examined the activity of DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) stably expressed in polarized cystic fibrosis bronchial epithelial cells (CFBE41o(-)) human airway cells and Fisher Rat Thyroid (FRT) cells following treatment with low temperature and a panel of small molecule correctors of DeltaF508 CFTR misprocessing. Corr-4a increased DeltaF508 CFTR-dependent Cl(-) conductance in both cell types, whereas treatment with VRT-325 or VRT-640 increased activity only in FRT cells. Total currents stimulated by forskolin and genistein demonstrated similar dose/response effects to Corr-4a treatment in each cell type. When examining the relative contribution of forskolin and genistein to total stimulated current, CFBE41o(-) cells had smaller forskolin-stimulated I(sc) following either low temperature or corr-4a treatment (10-30% of the total I(sc) produced by the combination of both CFTR agonists). In contrast, forskolin consistently contributed greater than 40% of total I(sc) in DeltaF508 CFTR-expressing FRT cells corrected with low temperature, and corr-4a treatment preferentially enhanced forskolin dependent currents only in FRT cells (60% of total I(sc)). DeltaF508 CFTR cDNA transcript levels, DeltaF508 CFTR C band levels, or cAMP signaling did not account for the reduced forskolin response in CFBE41o(-) cells. Treatment with non-specific inhibitors of phosphodiesterases (papaverine) or phosphatases (endothall) did not restore DeltaF508 CFTR activation by forskolin in CFBE41o(-) cells, indicating that the Cl(-) transport defect in airway cells is distal to cAMP or its metabolism. The results identify important differences in DeltaF508 CFTR activation in polarizing epithelial models of CF, and have important implications regarding detection of rescued of DeltaF508 CFTR in vivo.
Asunto(s)
Cloruros/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Fibrosis Quística/metabolismo , Animales , Células Cultivadas , Colforsina/farmacología , AMP Cíclico/metabolismo , Células Epiteliales/metabolismo , Genisteína/farmacología , Humanos , Transporte Iónico , Inhibidores de Fosfodiesterasa/farmacología , Monoéster Fosfórico Hidrolasas/antagonistas & inhibidores , Ratas , Ratas Endogámicas F344 , TemperaturaRESUMEN
The confined variational method is used to generate a basis of correlated Gaussians to describe the interaction region wave function for positron scattering from the H2 molecule. The scattering length was approximately = -2.7a(0) while the zero energy Z(eff) of 15.7 is compatible with experimental values. The variation of the scattering length and Z(eff) with internuclear distance was surprisingly rapid due to virtual state formation at R approximately = 3.4a(0).
RESUMEN
AIM: A direct association between intraoperative use of red blood cell (RBC) transfusion and perioperative mortality in patients undergoing aortic aneurysm surgery has not been studied before. METHODS: One thousand patients (mean age, 69.0 +/- 10.0 years; males 810) who underwent acute or elective abdominal or thoracoabdominal aortic aneurysm surgery between January 1999 and April 2007 at Semmelweis Medical University (Budapest, Hungary), were studied. Patients were evaluated for clinical risk factors, chronic medication use and surgical characteristics. Propensity score analysis was used to adjust for the potential bias in the intraoperative use of RBC transfusion. Multivariable logistic regression analyses were applied to study the association between the likelihood of intraoperative use of RBC transfusion and mortality occurring within 30 days of surgery. RESULTS: Perioperative mortality occurred in 85 (8.5%) patients. Thirty-day mortality was significantly higher in patients who received intraoperative RBC transfusion compared to patients who did not receive it (1 or 2 units of RBCs, crude odds ratio [OR]: 6.2, 95% confidence interval [CI]: 1.8-21.0; P = 0.003; 3 or more units, OR: 35.7, 95% CI: 11.1-115.4; P < 0.0001). Even after correction for other baseline covariates and propensity for RBC transfusion intraoperative use of RBC transfusion was associated with increased 30-day mortality (1 or 2 units of RBCs, OR: 4.6, 95% CI: 1.1-18.5; P = 0.03; 3 or more units, OR: 4.0, 95% CI: 1.0-16.0; P = 0.05). CONCLUSIONS: Intraoperative use of RBC transfusion in patients with acute or elective aortic aneurysm surgery is independently associated with an increased incidence of perioperative mortality.
Asunto(s)
Aneurisma de la Aorta Abdominal/mortalidad , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta Torácica/cirugía , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión de Eritrocitos/mortalidad , Procedimientos Quirúrgicos Vasculares/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos como Asunto , Femenino , Hematócrito , Humanos , Cuidados Intraoperatorios , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Puntaje de Propensión , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Adulto JovenRESUMEN
The effect of deuteration on the 13C linewidths of U-13C, 15N 2D crystalline bacteriorhodopsin (bR) from Halobacterium salinarium, a 248-amino acid protein with seven-transmembrane (7TM) spanning regions, has been studied in purple membranes as a prelude to potential structural studies. Spectral doubling of resonances was observed for receptor expressed in 2H medium (for both 50:50% 1H:2H, and a more highly deuterated form) with the resonances being of similar intensities and separated by <0.3 ppm in the methyl spectral regions in which they were readily distinguished. Line-widths of the methyl side chains were not significantly altered when the protein was expressed in highly deuterated medium compared to growth in fully protonated medium (spectral line widths were about 0.5 ppm on average for receptor expressed both in the fully protonated and highly deuterated media from the C delta, C gamma 1, and C gamma 2 Ile 13C signals observed in the direct, 21-39 ppm, and indirect, 9-17 ppm, dimensions). The measured 13C NMR line-widths observed for both protonated and deuterated form of the receptor are sufficiently narrow, indicating that this crystalline protein morphology is suitable for structural studies. 1) decoupling comparison of the protonated and deuterated bR imply that deuteration may be advantageous for samples in which low power 1H decoupling is required.
Asunto(s)
Bacteriorodopsinas/química , Espectroscopía de Resonancia Magnética/métodos , Isótopos de Carbono , Cristalografía/métodos , Deuterio , Halobacterium salinarum/metabolismo , Membrana Púrpura/metabolismoRESUMEN
BACKGROUND: Dihydropiridine calcium-channel blockers are often used as an alternative to beta-blockers for the treatment of hypertension in patients undergoing aortic aneurysm surgery. We studied the relation between dihydropiridine calcium-channel blocker use and perioperative mortality in patients undergoing aortic aneurysm surgery. METHODS: We studied 1000 patients [mean (range) age, 69 (22-95) yr; males 810] who underwent acute or elective abdominal or thoracoabdominal aortic aneurysm surgery between January 1999 and April 2007, at Semmelweis Medical University (Budapest, Hungary). Patients were evaluated for clinical risk factors, chronic medication use, and surgical characteristics. Propensity score analysis was used to adjust for the potential bias in dihydropiridine calcium-channel blocker use. Multivariable logistic regression analyses were applied to study the association between the likelihood of dihydropiridine calcium-channel blocker use and mortality occurring within 30 days of surgery. RESULTS: Perioperative mortality occurred in 85 (8.5%) patients. Thirty-day mortality was significantly higher in dihydropiridine calcium-channel blocker users compared with non-users, 14.0% vs 6.0%; crude odds ratio (OR) 2.6, 95% confidence interval (CI): 1.6-4.0, P<0.0001. Even after correcting for other baseline covariates and propensity for these agents dihydropiridine calcium-channel blocker use was associated with increased 30-day mortality, OR (95% CI) 2.5(1.3-4.6), P=0.003. CONCLUSIONS: Dihydropiridine calcium-channel blocker use in patients with acute or elective aortic aneurysm surgery is independently associated with an increased incidence of perioperative mortality.
Asunto(s)
Antihipertensivos/efectos adversos , Aneurisma de la Aorta/cirugía , Bloqueadores de los Canales de Calcio/efectos adversos , Dihidropiridinas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/administración & dosificación , Aneurisma de la Aorta/mortalidad , Bloqueadores de los Canales de Calcio/administración & dosificación , Dihidropiridinas/administración & dosificación , Esquema de Medicación , Métodos Epidemiológicos , Femenino , Humanos , Hungría/epidemiología , Masculino , Persona de Mediana Edad , Atención Perioperativa/efectos adversos , Atención Perioperativa/métodos , Complicaciones Posoperatorias/mortalidadRESUMEN
AIM: Recently, the clinical significance of aprotinin-induced renal dysfunction and other end-organ complications in patients undergoing cardiac surgery has engendered substantial controversy. Therefore, we assessed the effect of aprotinin on end-organ complications in patients undergoing cardiac surgery. METHODS: Data of 674 patients (mean age 65.4 +/- 11.0 years, 457 males) undergoing cardiac surgery between January 1 and December 31, 2005 at Semmelweis University were used for the analyses. Preoperative, intraoperative and postoperative clinical and surgical variables were recorded. Patients administered aprotinin received the drug either as a low-dose regimen, a loading dose of 1 million kallikrein-inhibitor units (KIU), 1 million KIU in pump, and 1 million KIU post pump (or continuous infusion of 0.25 million KIU per hour); or a high-dose regimen, a loading dose of 2 million KIU, 2 million KIU in pump, and 2 million KIU post pump (or continuous infusion of 0.5 million KIU per hour). The outcomes were renal complications defined as a 25% reduction in postoperative calculated creatinine clearance compared to the preoperative baseline or renal failure requiring dialysis; and the composite of renal, cardiovascular and cerebrovascular complications and all-cause mortality. RESULTS: Patients underwent coronary artery bypass surgery (63%), valvular (27%) or a combination (5%) and surgery on the ascending aorta (5%). There were 550 patients (81.6%) who received aprotinin treatment. In multivariate regression analyses when the relation between high or low dose aprotinin compared to no aprotinin was evaluated, the likelihood of renal complications [high dose: odds ratio (OR)=1.4, 95% confidence interval (CI), 0.6-3.0, P=0.4; low dose: OR=1.2, 95%CI, 0.7-2.3, p=0.5], and the composite outcome variable (high dose: OR=1.6, 95%CI, 0.8-3.4, P=0.2; low dose: OR=1.3, 95%CI, 0.7-2.3, P=0.4) were not significantly increased. CONCLUSION: Our analysis suggests that aprotinin use in either a high or low dose regimen was not associated with an increase in adverse end-organ complications.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Aprotinina/efectos adversos , Procedimientos Quirúrgicos Cardíacos , Complicaciones Intraoperatorias/inducido químicamente , Inhibidores de Serina Proteinasa/efectos adversos , Anciano , Aprotinina/administración & dosificación , Distribución de Chi-Cuadrado , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Inhibidores de Serina Proteinasa/administración & dosificación , Resultado del TratamientoRESUMEN
Marijuana is a widely abused recreational drug well known for its psychoactive properties. Cannabinoids, the active ingredients of marijuana, elicit their neurobehavioral effects by interacting with the CB1 cannabinoid receptor subtype, expressed primarily in the brain but also present in some peripheral tissues. A second receptor subtype, the CB2 receptor, is expressed on cells of the immune system and is thought to be responsible for the immunosuppressant effects of cannabinoids. Recently, endogenous lipidlike substances have been identified, including arachidonyl ethanolamide (anandamide) and 2-arachidonyl glyceride, that bind to cannabinoid receptors and mimic many of the neurobehavioral effects of plant-derived cannabinoids. Both plant-derived cannabinoids and the endogenous ligands have been shown to elicit hypotension and bradycardia via activation of peripherally located CB1 receptors. Possible underlying mechanisms include presynaptic CB1 receptor mediated inhibition of norepinephrine release from peripheral sympathetic nerve terminals, and/or direct vasodilation via activation of vascular cannabinoid receptors. The latter may also be the target of endocannabinoids of vascular endothelial origin. Recent studies indicate that a peripheral endogenous cannabinoid system in circulating macrophages and platelets is activated in hemorrhagic and septic shock and may contribute to the hypotension associated with these conditions via activation of vascular cannabinoid receptors. The potential role of this mechanism in human shock conditions is under investigation.
Asunto(s)
Cannabinoides/farmacología , Corazón/efectos de los fármacos , Choque/metabolismo , Animales , Moduladores de Receptores de Cannabinoides , Cannabinoides/metabolismo , Humanos , Estructura Molecular , Plantas/química , Receptores de Cannabinoides , Receptores de Droga/metabolismoRESUMEN
We previously showed that in anesthetized rats anandamide elicits bradycardia and a triphasic blood pressure response: transient hypotension secondary to a vagally mediated bradycardia, followed by a brief pressor and prolonged depressor response, the latter two effects being similar to those of delta 9-tetrahydrocannabinol (THC). The prolonged depressor but not the pressor response was reduced after alpha-adrenergic receptor blockade or cervical spinal cord transection and was inhibited by the cannabinoid type 1 (CB1) receptor antagonist SR141716A, suggesting CB1 receptor-mediated sympathoinhibition as the underlying mechanism. Here we examined the relationship between sympathetic tone and the cardiovascular effects of anandamide by testing these effects in both conscious and anesthetized, normotensive and spontaneously hypertensive rats. In urethane-anesthetized normotensive rats, SR141716A inhibited the prolonged depressor and bradycardic effects of anandamide and THC with similar potency, whereas it did not affect the pressor response to either agent. Anadamide caused similar hypotension in spontaneously breathing and in paralyzed, mechanically ventilated rats, suggesting that the hypotension is not secondary to respiratory effects. In conscious normotensive rats, anandamide elicited transient vagal activation and a brief pressor response, but the prolonged hypotensive component was absent. SR141716A potentiated and prolonged the brief pressor response to anandamide, suggesting that the depressor response may have been masked by an increased pressor response. All three phases of the anadamide response were present in both anesthetized and conscious spontaneously hypertensive rats, and the hypotensive component, inhibited by SR141716A in both, was more prolonged in the absence (> 50 minutes) than the presence (10 to 15 minutes) of anesthesia. We conclude that anandamide causes a non-CB1 receptor-mediated pressor and a CB1 receptor-mediated prolonged depressor response. The depressor response can be elicited in both conscious and anesthetized animals, but its magnitude depends on preexisting sympathetic tone.
Asunto(s)
Ácidos Araquidónicos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/fisiopatología , Anestesia , Animales , Relación Dosis-Respuesta a Droga , Endocannabinoides , Inyecciones Intravenosas , Masculino , Alcamidas Poliinsaturadas , Ratas , Ratas Endogámicas SHR , Ratas Sprague-DawleyRESUMEN
Cannabinoids, including the endogenous ligand anandamide (arachidonyl ethanolamide), elicit pronounced hypotension in rats via activation of peripherally located CB1 cannabinoid receptors, which have been also implicated in endotoxin (lipopolysaccharide [LPS])-induced hypotension. The present study was designed to test the role of vascular CB1 receptors in cannabinoid- and endotoxin-induced mesenteric vasodilation. In the isolated, buffer-perfused rat mesenteric arterial bed precontracted with phenylephrine, anandamide induced long-lasting (up to 60 minutes) dose-dependent vasodilation (ED50: 79+/-3 nmol; maximal relaxation: 77+/-2%), inhibited by 0.5 to 5.0 micromol/L of the selective CB1 receptor antagonist SR141716A. Low doses of the calcium ionophore ionomycin also caused mesenteric vasodilation inhibited by SR141716A. The metabolically stable analogue R-methanandamide elicited mesenteric vasodilation (ED50: 286+/-29 nmol), whereas the potent synthetic CB1 receptor agonists WIN 55212-2 and HU-210 caused no change in vascular tone or only a minor dilator effect not affected by SR141716A, respectively. The endogenous ligand 2-arachidonyl glycerol caused no change in vascular tone, whereas Delta9-tetrahydrocannabinol and arachidonic acid caused mesenteric vasoconstriction. After endothelial denudation, the dilator response to anandamide was slightly reduced and was no longer inhibited by SR141716A. In preparations from LPS-pretreated rats, SR141716A alone caused a significant and prolonged increase in perfusion pressure, whereas it had no such effect in control preparations perfused in vitro with or without LPS or after endothelial denudation in preparations from rats pretreated with LPS. We conclude that anandamide-induced mesenteric vasodilation is mediated by an endothelially located SR141716A-sensitive "anandamide receptor" distinct from CB1 cannabinoid receptors and that activation of such receptors by an endocannabinoid, possibly anandamide, contributes to LPS-induced mesenteric vasodilation in vivo.
Asunto(s)
Ácidos Araquidónicos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Endotelio Vascular/fisiología , Arterias Mesentéricas/fisiología , Músculo Liso Vascular/fisiología , Vasodilatación/fisiología , Animales , Ácido Araquidónico/farmacología , Moduladores de Receptores de Cannabinoides , Dronabinol/farmacología , Endocannabinoides , Glicéridos/farmacología , Ligandos , Masculino , Arterias Mesentéricas/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Piperidinas/farmacología , Alcamidas Poliinsaturadas , Pirazoles/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Droga/antagonistas & inhibidores , Receptores de Droga/fisiología , Rimonabant , Vasoconstricción , Vasodilatación/efectos de los fármacosRESUMEN
We studied the effects of the endogenous cannabinoid ligand anandamide on blood pressure, single unit activity of barosensitive neurons in the rostral ventrolateral medulla, and postganglionic splanchnic sympathetic nerve discharge in urethane-anesthetized rats. In rats with an intact baroreflex, an intravenous bolus of 4 mg/kg anandamide caused a triphasic blood pressure response: transient hypotension, followed by a brief pressor and more prolonged depressor phase. Anandamide evoked a "primary" increase in neuronal firing coincident with its pressor effect and a "secondary," baroreflex-mediated rise coincident with its depressor effect at both sites. Pretreatment of rats with phentolamine or trimethaphan did not inhibit either the pressor response or the primary increase in splanchnic nerve discharge elicited by anandamide. In barodenervated rats, electrical stimulation of the rostral ventrolateral medulla increased blood pressure and splanchnic nerve discharge. Anandamide treatment blunted the rise in blood pressure without affecting the increase in splanchnic nerve discharge. Anandamide did not affect the rise in blood pressure in response to an intravenous bolus dose of phenylephrine. The results indicate that (1) the brief pressor response to anandamide is not sympathetically mediated, and (2) the prolonged hypotensive response to anandamide is not initiated in the central nervous system, in ganglia, or at postsynaptic adrenergic receptors but is due to a presynaptic action that inhibits norepinephrine release from sympathetic nerve terminals in the heart and vasculature.
Asunto(s)
Ácidos Araquidónicos/farmacología , Presión Sanguínea/efectos de los fármacos , Cannabinoides/farmacología , Anestesia , Animales , Dronabinol/farmacología , Endocannabinoides , Masculino , Alcamidas Poliinsaturadas , Presorreceptores/fisiología , Ratas , Ratas Sprague-Dawley , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
Diurnal rhythm of plasma beta endorphin was established with the highest level in the morning and the lowest one at midnight in normotensive subjects and also in patients with essential hypertension. Clonidine (300 micrograms daily) significantly increased plasma beta endorphin concentrations only in the hypertensive patients. The significant linear correlation between the increase in plasma beta endorphin concentration and the decrease in blood pressure (both systolic and diastolic) in these patients may point to the role of this endogenous opioid in the antihypertensive action of clonidine.
Asunto(s)
Ritmo Circadiano , Clonidina/uso terapéutico , Endorfinas/sangre , Hipertensión/sangre , Clonidina/farmacología , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión/tratamiento farmacológico , betaendorfinaRESUMEN
Daily doses of 0.3 mg clonidine and 3 mg guanfacine were equiactive in decreasing blood pressure and heart rate in 17 subjects with essential hypertension. Clonidine decreased cardiac output and guanfacine decreased total peripheral resistance, while clonidine had no effect on stroke volume but guanfacine increased it. Both clonidine and guanfacine decreased plasma renin activity. Naloxone, 0.4 mg iv, reversed the antihypertensive effect of clonidine but was ineffective even at higher doses (1.6 mg iv) when subjects were treated with placebo or guanfacine. It is suggested that the hemodynamic differences between the two centrally acting alpha 2-adrenoceptor agonist antihypertensive drugs may at least in part result from the involvement of opioid mechanisms only in the action of clonidine.
Asunto(s)
Clonidina/uso terapéutico , Guanidinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Fenilacetatos/uso terapéutico , Adulto , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Clonidina/antagonistas & inhibidores , Guanfacina , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Indio , Inyecciones Intravenosas , Persona de Mediana Edad , Naloxona/farmacología , Radioisótopos , Renina/sangreRESUMEN
Ethanol administered i.v. or into the nucleus tractus solitarii (NTS) of rats anaesthetized with urethane inhibits baroreflex bradycardia elicited by phenylephrine. This effect is prevented or reduced by pretreatment of rats with 3-mercaptopropionic acid, bicuculline, or RO 15-4513. Intra-NTS injection of muscimol also inhibits baroreflex bradycardia and causes a pressor response which is potentiated by intra-NTS ethanol. It is proposed that ethanol inhibits baroreflex bradycardia, at least in part, by potentiating the action of endogenous gamma-aminobutyric acid (GABA) at GABAA receptors in the NTS or its vicinity.