Drug Evaluations Cardiovascular & Renal: Biology of angiotensin II receptor inhibition with a focus on losartan: A new drug for the treatment of hypertension

Abstract

Pharmacological blockade of the renin-angiotensin-aldosterone system with angiotensin converting enzyme (ACE) inhibitors has advanced knowledge of the mechanisms by which blood pressure is regulated as well as provided new approaches to the treatment of essential hypertension and congestive heart failure. Although the idea that primary or essential hypertension may be caused by an increase in the activity of the renin-angiotensin system was originally proposed by Page in 1967 in his mosaic theory of arterial hypertension, the identification of molecular variants in the genes that encode the components of the renin-angiotensin system now begins to substantiate a role for this hormonal system in the causation of hypertension. The cumulative results of basic investigations and clinical research culminated with the introduction of a new class of orally active antihypertensive drugs which specifically target angiotensin (Ang) II receptors as a means to control blood pressure. Emerging results from the clinical use of selective Ang II receptor antagonists suggest that these antihypertensive agents provide an opportunity for selective and specific treatment of cardiovascular disorders associated with excess production or activity of Ang II. Furthermore, this new class of drugs may extend the medical armamentarium of hypertension therapy to the prevention of coronary artery disease, stroke and cardiac and renal failure. The specific action of these agents on Ang II receptors represents a more direct and specific approach to the correction of the pathological pressor and vascular proliferative actions of Ang II. In this article, we review the pharmacological rationale and current therapeutic efficacy of losartan potassium, the first prototypical Ang II antagonist approved for the treatment of high blood pressure.

Key Words:

• angiotensin II
• angiotensin-(1-7)
• angiotensin-(2-8)
• angiotensin converting enzyme
• angiotensinogen
• angiotensin receptor subtypes
• congestive heart failure
• DuP 753
• essential hypertension
• losartan
• MK-954
• renin