Central actions of angiotensin in cardiovascular control: Multiple roles for a single peptide

Abstract

Angiotensin II (ANG II) acts peripherally as a hormone, with actions on the vasculature, adrenals, and kidney. In addition, certain actions of ANG II in the central nervous system are directed toward cardiovascular control and fluid volume homeostasis. Dense binding sites for ANG II are found at circumventricular organs, which apparently have the ability to relay information to cardiovascular centers via neural circuitry. Microinjection of ANG II into the subfornical organ (SFO) or area postrema (AP) produces site-specific increases in blood pressure. In addition, electrophysiological studies demonstrate profound effects of ANG II, acting at the SFO, on activity of neurohypophysial neurons and release of oxytocin and vasopressin, which can be antagonized by ANG II blockers or attenuated by SFO lesions. Evidence from microinjection, electrophysiological, and lesion studies indicate a complex interaction between central sites involved in mechanisms of cardiovascular control: the SFO, AP, organum vasculosum of the lamina terminalis, and paraventricular and supraoptic nuclei of the hypothalamus. Not only is ANG II a humoral messenger in this central scenario, but evidence suggests it acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control.

Heart failure and the brain: new perspectives

“…Although currently used ACE inhibitors, AT 1 receptor blockers and MC receptor antagonists may act upon the CNS, either by crossing blood-brain barrier (95,150,174) or by acting upon the circumventricular organs that lack a blood-brain barrier (50,137,140,142), their design and clinical usage target peripheral endpoints. Ideally, it might be possible to continue treating the adverse peripheral consequences of RAAS, e.g., vasoconstriction, cardiac and vascular remodeling, while increasing the ability of these agents to penetrate brain regions whose intrinsic RAAS activity may actually be augmented by predominantly peripheral ACE inhibition in heart failure.…”

“…Ideally, it might be possible to continue treating the adverse peripheral consequences of RAAS, e.g., vasoconstriction, cardiac and vascular remodeling, while increasing the ability of these agents to penetrate brain regions whose intrinsic RAAS activity may actually be augmented by predominantly peripheral ACE inhibition in heart failure. The forebrain circumventricular organs, rich in ACE (140,143) and AT 1 receptors (50,142) and lacking the protection of the blood-brain barrier, would appear to be easily accessible targets for therapeutic intervention.…”

AT4 receptor binding in the developing rabbit

“…The principal physiological functions of AngII are related to water homeostasis and cardiovascular regulation. These effects are mediated by virtue of AngII's action on both peripheral tissues and the central nervous system (CNS) (Phillips, 1987;Ferguson and Wall, 1992). These physiological responses are invoked through the interaction of AngII and membranebound receptors, of which there are two major subtypes, AT 1 and AT 2 .…”

Microinjections of Angiotensin II into the Supraoptic and Paraventricular Nuclei Produce Potent Antidiureses by Vasopressin Release Mediated through Adrenergic and Angiotensin Receptors

“…The primary action site(s) of Ang II is suggested to be an organ(s) surrounding the an teroventral third ventricle (AV3V), from the results that lesion or ablation of AV3V inhibits the antidiuretic effects (1,3). There are Ang II-sensitive neurons from the circum ventricular organs to the hypothalamic paraventricular nucleus (PVN) (6,7). The PVN, being adjacent to the wall of the third ventricle, includes cell bodies of vasopres sin-containing neurons.…”

“…Vasopres sin-containing neurons are activated by Ang II (12 14). Also, Ang II receptors, neurons and terminals of Ang II containing neurons are involved in the SON, as well as in the PVN (6,8,15).…”