ABSTRACT
El óxido nítrico es una molécula neurotransmisora, mediadora de importantes funciones como la vasodilatación, estimulación de la síntesis de músculo liso vascular y antiagregación plaquetaria. El óxido nítrico es continuamente sintetizado y liberado desde el endotelio en condiciones fisiológicas. La inhibición crónica de la producción de óxido nítrico conduce a hipertensión arterial severa; por otra parte la hipertensión arterial se asocia con otros factores de riesgo, como lo es la sensibilidad a la sal. A pesar de que la hipertensión arterial inducida por sodio fue descrita hace medio siglo, aún se desconoce su etiología en humanos, y las implicaciones del óxido nítrico en su aparición. a) La ingesta elevada de sodio inhibe la producción del óxido nítrico; este efecto se revierte con la ingestión de sal. b) en sujetos obesos, la corrección de alteraciones metabólicas asociadas es capaz de corregir la sensibilidad a la sal y por lo tanto, de disminuir la hipertensión arterial en los individuos sal sensibles. También restablece la bioactividad normal del óxido nítrico. Estos hallazgos permiten afirmar que los factores de riesgo adquiridos juegan un papel importante en la patogénesis de la sensibilidad a la sal asociada a la obesidad, y que la corrección de la adiposidad abdominal mejora las anomalías metabólicas asociadas, reduce la reactividad de la presión arterial al sodio y mejora la producción de óxido nítrico.
Nitric oxide, as a neurotransmitter molecule, is a mediator of important functions including vasodilatation, synthesis of vascular smooth muscle and anti-aggregation of platelets. Under physiological conditions nitric oxide is synthesized and released from the endothelium. The chronic inhibition of nitric oxide production leads to severe hypertension; moreover hypertension is associated with other risk factors, such as salt sensitivity. Although hypertension induced by sodium was described half a century ago, its etiology remains unclear as well as the involvement of nitric oxide. A) high sodium intake inhibits the production of nitric oxide; this effect is reversed by reducing salt intake. B) in obese subjects, the reduction of central adiposity and the correction of related metabolic abnormalities can alter the salt sensitivy, and thereby decrease blood pressure in salt-sensitive individuals. It also restores the normal bioactivity of nitric oxide. These findings confirm the important role of risk factors in the pathogenesis of salt sensitivy associated with obesity, and that the correction of abdominal fat improves metabolic abnormalities, leading to the lowering of salt sensitivy and to an improvement in the production of nitric oxide.
Subject(s)
Humans , Cardiovascular Agents , Endothelium/physiology , Hypertension/physiopathology , Nitric Oxide , Obesity/physiopathology , Sodium/adverse effects , Cardiovascular Physiological Phenomena , Risk FactorsABSTRACT
The mechanism involved in the regulation of dopamine (DA) rease from mesocortical dopaminergic neurons were studied. Prefrontal cortical slices (PFC) were incubated with 3H-Da in the presence of 0.3 uM desipramine. Under these conditions,6 to 10% of 3H-norepinephrine was formed. After incubation, the slices were superfused (2 slices/chamber). At 45 minutes of washout, a constant rate of efflux of 3H- norepinephrine was obtained; 1.46+/- 0.1 % of the 3H present in the slices was released every 5 minutes. Electrical stimulation (1Hz, 120 pulses) produced a calcium dependent increase in the outflow of 3H- products above prestimulation levels (3.4+/_ 0.1%) Since the release of a neurotransmitter may be modulated by presynaptic receptors others than autoreceptors, we investigated the pharmacology of presynaptic receptors monitoring the effects of DA, norepinephrine, serotonine, acetylcholine, Gaba and CCK agonists and antagonists on the electrically evoked relase of DA. Apomorphine, LY171555 and bromocriptine inhibited Da realese. Maximun inhibition of release values for these drugs were 66 and 59% (EMAX) and those for EC50 were 25, 29 and 20 nM, respectively. Haloperidol antagonized the inhibitory effect of DA agonist whereas phentolamine hsd no effect. Haloperidol produced singnificant increase in the stimulation- evoked release of 3H (76%). The other agents did not modify DA release from PFC slices. These results suggest that DA release is modulated by auyoreceptors whereas the presynaptic noradrenergic, cholinergic serotoninergic, Gabaergic and CCK receptors do not appear to play a significant role in the regulation of DA