Revelation on the potency of α1-blockers parallel blockade of angiotensin II receptor: A new finding

Abstract

Context: The problem of hypertension has gained enormous proportions in the past decade. Multifactorial etiology and complex pathophysiology of the disease has rendered the treatment of the disease a hard task. Sympathetic nervous system and the reninangiotensinaldosterone system are primary contributors of blood pressure homeostasis. Objective: Structural similarities were identified among AT 1 and α 1-antagonists, initiating a speculation that α 1-antagonists could possibly block the AT 1 receptor and vice-versa. Methods: To corroborate this speculation, we screened prototypical α 1-antagonists such as prazosin, doxazosin, and terazosin for antagonism of angiotensin II on rat aortic strips. We also examined the AT 1 antagonists losartan, valsartan, and olmesartan for their possible antagonistic effect, on contractions of rat aortic strips induced by phenylephrine. Results: To our astonishment, we found that prazosin and its analogs which have been reported to have α 1-antagonistic activity only, were able to shift concentration response curves of angiotensin II. Conclusion: Our findings suggest that the potent antihypertensive effect of prazosin-type α 1-antagonists is not purely due to α 1- receptor blocking activity of these compounds but also due to blockade of AT 1 receptors. This finding may lead to the development of more potent dual inhibitors which would prove to be of immense value in the control of the scourge of hypertension. © 2012 Informa Healthcare USA, Inc.