The role of angiotensin II receptors and their antagonists in hypertension.
The octapeptide angiotensin II is the major effector of the renin-angiotensin-aldosterone system. Angiotensin II causes a variety of potentially noxious biological effects, such as vasoconstriction, a rise in blood pressure, release of aldosterone, enhancement of the effect of catecholamines, and vascular and myocardial hypertrophy, including remodeling of the heart after myocardial infarction. All of these noxious effects of angiotensin II are mediated by angiotensin II receptors (AT receptors) of the AT1 subtype. The functional effects of AT2 receptors, which have been characterized by means of biochemical techniques, are so far not clearly identified. Stimulation of the AT2 receptor by means of angiotensin II is assumed to counteract vascular/myocardial remodeling and possibly to induce vasodilation. Accordingly, AT1 and AT2 receptors are believed to provoke opposite effects. It has drawn attention that fetal tissues contain a high density of AT2 receptors, which is lowered significantly after birth. The identification and analysis of AT receptors has been greatly stimulated by the development of non-peptidergic AT1 receptor antagonists, of which losartan is the prototype. It is so far unclear whether AT receptors are activated in hypertensive disease. A survey will be made of the hemodynamic effects of AT1 receptor antagonists, their interaction with AT receptors, and the probably important role of the sympathetic nervous system involved in the antihypertensive action of AT receptor antagonists.
van Zwieten
P A
PA
Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D011945:Receptors, Angiotensin