Lack of interaction between a hypertonic NaCl stimulus and the brain renin-angiotensin system

Sodium and the renin-angiotensin system (RAS) participate in the regulation of cardiovascular function, in part via activation of central nervous system (CNS) mechanisms. Because intraventricular (IVT) administration of either hypertonic sodium chloride (NaCl) or angiotensin II (ANG II) elicits similar effects (i.e., natriuresis, hypertension, increased drinking, and enhanced vasopressin release) a common and final pathway may be involved. With this in mind, we measured the effect of an IVT injection (third or lateral ventricle) of 0.6 M NaCl on postganglionic renal nerve activity (RNA) and blood pressure in morphine-pentobarbital-anesthetized dogs before and after blockade of the brain RAS with either captopril or [Sar1,Ile8]ANG II. Both vagus and carotid sinus nerves were cut to avoid impingement of the baroreceptor reflex on the measured variables. IVT injection of 0.6 M NaCl produced a prominent hypertensive response and tachycardia associated with a 59 +/- 9% increase in RNA. These changes were statistically significant (P less than 0.001), correlated with each other, and were abolished by administration of hexamethonium chloride (10 mg/kg iv). Blockade of central ANG II receptors with [Sar1,Ile8]ANG II was without effect. However, in dogs given IVT SQ 14,225, there was a slight increase in baseline RNA before injection of 0.6 M NaCl; in addition, both the pressor and heart rate responses to the stimulus of hypertonic NaCl were further augmented. These results demonstrate that central administration of hypertonic NaCl in baroreceptor-denervated dogs produces marked activation of sympathetic nerve activity via mechanisms other than activation of the brain RAS.