The Angiotensin II Type 1 Receptor Antagonists

Abstract

The angiotensin II (AII) type 1 receptor antagonists represent a new pharmacologic class of drugs that are specifically designed to displace AII from its type 1 receptor subtype. These drugs antagonize AII-induced biologic actions, including smooth-muscle contraction, sympathetic pressor mechanisms, and aldosterone release. Initial clinical trials suggest that these drugs are effective in the treatment of essential hypertension and hypertensive patients with intrinsic renal disease. Thus, they are the newest addition to the therapeutic armamentarium for the treatment of hypertensive diseases. We review the developmental history and pharmacology of the AII type 1 receptor antagonists. We specifically discuss the following factors: mechanism(s) of action; members under clinical investigation; effects on renal function, salt and water excretion, and plasma renin activity, plasma AII type 1, and plasma aldosterone concentrations; and efficacy and safety. Given the demonstrable benefits of AII type 1 receptor blockade, these drugs should achieve broad utility in the treatment of hypertensive diseases.

AT₁-Receptor Antagonists Abolish Glomerular MCP-1 Expression in a Model of Mesangial Proliferative Glomerulonephritis

“…The concentrations of losartan and irbesartan used were obtained from the literature and no study has hitherto directly compared the efficiency of these two drugs [17, 18, 19, 20]. However, both AT 1 -receptor antagonists raised the PRA to a similar extent, an effect known to be caused by interference with the negative feedback of ANG II on renin synthesis, suggesting that the concentrations of the two drugs used may be comparable.…”

“…These doses of losartan and irbesartan have previously been used by others to block AT 1 receptors and reduce systolic blood pressure to a similar extent [17, 18, 19, 20]. …”

Losartan and Reversible Psychosis

“…Losartan and its me tabolites are eliminated mainly in biliary ex cretion, and therefore a lower starting dose is recommended in patients with hepatic dys function: the patient described docs not have renal or hepatic impairment. Although the plasma angiotensin-II concentration is in creased during long-term drug therapy, abrupt withdrawal is not associated with acute rebound hypertension [2]. This may be due to the short half-life (2 It) of losartan and the long half-life (6-9 h) of the metabolite, which is extremely effective as an antihypertensivc.…”

“…In clinical trials, losartan has been very effective for the treatment of hypertension [2]. Although circulating angiotensin II can act on the central nervous system, the brain possesses its own renin-angiotensin system [3,4]; thus losartan has action on the brain as well.…”

Bioanalytical Method Development and Validation for Quantitative Estimation of Valsartan by LC-MS/MS in Human Plasma

“…It is an angiotensin II receptor (AT) blocker particularly has high affinity to bind AT1 subtype receptor. Valsartan produce vasodilatation effect on blood vessels and decrease in vascular resistance and blood pressure by selectively inhibits the binding of angiotensin II to AT1, which is found in many tissues such as vascular smooth muscle and the adrenal glands [3][4][5][6].…”