Actions of Angiotensin II

ACTIONS OF ANGIOTENSIN II

Angiotensin II exerts important actions at vascular smooth mus-cle, adrenal cortex, kidney, heart, and brain via the receptors described below. Through these actions, the renin-angiotensin system plays a key role in the regulation of fluid and electrolyte balance and arterial blood pressure. Excessive activity of therenin-angiotensin system can result in hypertension and disorders of fluid and electrolyte homeostasis.

Blood Pressure

Angiotensin II is a very potent pressor agent—on a molar basis, approximately 40 times more potent than norepinephrine. The pressor response to intravenous ANG II is rapid in onset (10–15 seconds) and sustained during long-term infusions. A large com-ponent of the pressor response is due to direct contraction of vascular—especially arteriolar—smooth muscle. In addition, however, ANG II can also increase blood pressure through actions on the brain and autonomic nervous system. The pressor response to ANG II is usually accompanied by little or no reflex bradycar-dia because the peptide acts on the brain to reset the baroreceptor reflex control of heart rate to a higher pressure.

Angiotensin II also interacts with the autonomic nervous sys-tem. It stimulates autonomic ganglia, increases the release of epi-nephrine and norepinephrine from the adrenal medulla, and most important, facilitates sympathetic transmission by an action at adrenergic nerve terminals. The latter effect involves both increased release and reduced reuptake of norepinephrine. Angiotensin II also has a less important direct positive inotropic action on the heart.

Adrenal Cortex & Kidney

Angiotensin II acts directly on the zona glomerulosa of the adrenal cortex to stimulate aldosterone synthesis and release. At higher concentrations, ANG II also stimulates glucocorticoid synthesis. Angiotensin II acts on the kidney to cause renal vasoconstriction, increase proximal tubular sodium reabsorption, and inhibit the release of renin.

Central Nervous System

In addition to its central effects on blood pressure, ANG II acts on the central nervous system to stimulate drinking (dipsogenic effect) and increase the secretion of vasopressin and adrenocorti-cotropic hormone (ACTH). The physiologic significance of the effects of ANG II on drinking and pituitary hormone secretion is not known.

Cell Growth

Angiotensin II is mitogenic for vascular and cardiac muscle cells and may contribute to the development of cardiovascular hyper-trophy. It also exerts a variety of important effects on the vascular endothelium. Indeed, overactivity of the renin-angiotensin system has been implicated as one of the most significant factors in the development of hypertensive vascular disease. Considerable evi-dence now indicates that ACE inhibitors and ANG II receptor antagonists  slow or prevent morphologic changes (remodeling) following myocardial infarction that would other-wise lead to heart failure. The stimulation of vascular and cardiac growth by ANG II is mediated by other pathways, probably recep-tor and nonreceptor tyrosine kinases such as the Janus tyrosine kinase Jak2, and by increased transcription of specific genes .