Effects of l-NAME on cerebral metabolic, vasopressin, oxytocin, and blood pressure responses in hemorrhaged rats

Abstract

N G-nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), an inhibitor of NO synthase, or the vehicle artificial cerebrospinal fluid (aCSF; 5 μl) was administered intracerebroventricularly to conscious rats hemorrhaged (0.7 ml/min) to a 20% volume depletion. Hypotension was maximal 5 min after hemorrhage ended, with compensatory recovery to basal levels 20 min later, regardless of drug treatment.l-NAME, however, elevated ( P < 0.05) blood pressure (vs. aCSF controls) 40–45 min after intracerebroventricular administration. In normovolemic rats, l-NAME produced a significant pressor response and increased plasma levels of vasopressin (VP) and oxytocin (OT). After hemorrhage, both hormone levels increased, but only OT was further enhanced byl-NAME. Thus centrally produced NO tonically inhibits OT and VP secretion under basal normovolemic conditions and selectively inhibits OT release during hypovolemia. Hemorrhage increased the rates of glucose utilization in the neural lobe, indicative of enhanced efferent neural functional activity.l-NAME further enhanced the metabolic activity in the entire hypothalamoneurohypophysial system of hemorrhaged animals. Several other brain structures involved in the regulation of blood pressure and the stress response were also metabolically affected by the hemorrhage andl-NAME.