Functional roles of brain AT 1 and AT 2 receptors in the central angiotensin II pressor response in conscious young spontaneously hypertensive rats

Abstract

Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominately express AT 1 ANG II receptors. In contrast, AT 2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT 1 and AT 2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 μl) were determined 10 minutes after i.c.v. injection of either the AT 1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 10.0 μg), the AT 2 receptor ligand PD 123319 (3.5 × [10 −6, 10 −4, 10 −2, 10 0] μg), or both. In control rats, i.c.v. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner ( P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II-induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT 1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 μg of PD 123319 than when given alone ( P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG II-induced pressor effects may involve activation of multiple receptor subtypes.