Neurohumoral contributions to chronic angiotensin-induced hypertension.

A central pressor effect of angiotensin II (ANG II) has been implicated in the pathogenesis of several forms of experimental hypertension. Therefore, the present studies were designed to investigate mechanisms that contribute to hypertension resulting from selective stimulation of brain ANG II receptors by chronic intracerebroventricular (ICV) infusion of ANG II. Specifically, the role of the sympathetic nervous system, the pressor actions of vasopressin, and the direct vasoconstrictor effect of blood-borne ANG II were investigated in rats made hypertensive by 5- to 7-day ICV ANG II infusions (6 micrograms/h). Rats were chronically instrumented with indwelling arterial and venous catheters and a lateral cerebral ventricular cannula. Acute intravenous infusion of the competitive ANG II receptor antagonist [Sar1-Ala8]ANG II during the period of ICV ANG II infusion resulted in a moderate decrease in arterial pressure, indicating that an increase in blood-borne ANG II may account for a small component of the hypertensive response to ICV ANG II. Activation of the sympathetic nervous system appeared to be the major contributor to the elevated arterial pressure, since acute ganglionic blockade and combined alpha- and beta-adrenergic blockade produced greater depressor responses in rats made hypertensive with chronic ICV ANG II infusion than in normotensive rats. Furthermore, peripheral sympathectomy delayed hypertension development. Intravenous administration of a specific antagonist of the vascular vasopressin receptor did not cause a depressor response in rats made hypertensive with chronic ICV ANG II infusions. These studies demonstrate that a major mechanism involved in the pressor response to acute ICV ANG II injections, namely vasopressin release, does not appear to contribute to hypertension produced by chronic ICV infusions of ANG II. Rather, this form of hypertension is characterized predominantly by an increase in sympathetic vasoconstrictor tone and possibly by a mechanism activated by a small increase in circulating levels of ANG II.