Cardiovascular Actions of Angiotensin II in the Ventrolateral Medulla

Abstract

Angiotensin II (ANG II) has received considerable attention as a humoral regulator of cardiovascular homeostasis because of its well known actions at resistance vessels, its stimulatory effects on neurohormonal systems and its role as a potent dipsogen via actions in the hypothalamus. Furthermore, evidence obtained over the last 25 years has shown that circulating Ang II acts at restricted sites in the central nervous system lacking an intact blood- brain barrier to influence the regulation of the autonomic nervous system. ANG II enhances the activity of the sympathetic nervous system by an action of the peptide at the area postrema. Many aspects of ANG II involvement in circulatory homeostasis are directly related to the plasma concentration of this peptide. However, local tissue renin-angiotensin systems (RAS) have been recognized as contributing to the regulation of arterial pressure. Evidence shows that the brain contains a functional RAS. Angiotensinogen is a major protein component of cerebrospinal fluid (Brosnihan et al., 1987) and glial cells contain abundant mRNA necessary for the synthesis of the renin substrate (Deschepper et al., 1986). Immunohistochemical and anatomical studies have shown that ANG II and binding sites for this peptide are found in brain regions important in the regulation of hydromineral balance and cardiovascular function (Aguirre et al., 1989; Diz et al., 1986; Lind et al., 1985a,b; Speth et al., 1985). In the hypothalamus, circumventricular organs that respond to blood-borne ANG II by eliciting dipsogenic and pressor responses may utilize neural pathways exhibiting ANG II immunoreactivity.