Effects of central losartan on plasma renin and centrally mediated natriuresis

Because intracerebroventricular (ICV) infusion of hypertonic saline or angiotensin II (Ang II) both induce water drinking, vasopressin secretion, natriuresis and increased arterial pressure, the possibility that common neural pathways mediate responses to ICV Ang II and hypertonic saline has been investigated. This was done by testing the effect of ICV infusion of the Ang II antagonist losartan on the natriuretic and pressor responses to ICV hypertonic NaCl in sheep. The effect of ICV losartan on plasma renin concentration (PRC) was also investigated. Infusion of losartan (1 mg/hr) into a lateral ventricle prevented both natriuretic and pressor responses to infusion of 0.6 mol/liter NaCl into a lateral ventricle at 1 ml/hr. In another experiment, ICV losartan at 1 mg/hr caused a pronounced increase in the PRC of Na-depleted sheep, while ICV Ang II at 3 micrograms/hr decreased PRC. The results suggest that: (i) a central angiotensinergic pathway may mediate osmoregulatory responses to centrally administered hypertonic saline, and (ii) a central angiotensinergic pathway may have a tonic inhibitory influence on renin secretion in Na-depleted animals.