The pharmacology of carvedilol

Abstract

Carvedilol is a potent antihypertensive agent with a dual mechanism of action. At relatively low concentrations it is a competitive beta-adrenoceptor antagonist and a vasodilator, whereas at higher concentrations it is also a calcium channel antagonist. The antihypertensive activity of carvedilol is characterized by a decrease in peripheral vascular resistance, resulting from the vasodilator activity of the compound, with no reflex tachycardia, as a result of beta-adrenoceptor blockade. The antihypertensive activity of carvedilol is associated with an apparent "renal sparing" effect in that the reduction in mean arterial blood pressure does not compromise renal blood flow or urinary sodium excretion. Studies on the mechanism of action of carvedilol indicate that the compound is a potent competitive antagonist of beta 1- and beta 2-adrenoceptors with a dissociation constant (KB) of 0.9 nM at both beta-adrenoceptor subtypes. Carvedilol is also a potent alpha 1-adrenoceptor antagonist (KB = 11 nM), which accounts for most, if not all, of the vasodilating response produced by the compound. At concentrations above 1 microM, carvedilol is a calcium channel antagonist. This activity can be demonstrated in vivo at doses that represent the higher end of the antihypertensive dose-response curve. Although the calcium-channel blocking activity of carvedilol may not contribute to the antihypertensive activity of the compound, it may play a prominent role in certain peripheral vascular beds, such as the cutaneous circulation, where marked increases in blood flow are observed. The data indicate that carvedilol is an antihypertensive agent that is both a beta-adrenoceptor antagonist and a vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

<b>Carvedilol Prevents Myocardial Fibrosis in Hamsters</b>

“…5) Carvedilol is a β-blocker that also has α-blocking and antioxidant effects, which have been shown to reduce the mortality rate of patients with moderate to severe chronic cardiac failure by 35% to 65%, in addition to also lowering the rehospitalization rate. 3,4) In the present study, we assessed the effects of carvedilol [6][7][8] in another hamster model of dilated cardiomyopathy, the Bio 53.58 hamster (TO2), [9][10][11][12][13] with respect to the mortality rate, pathological changes of the myocardium, and MRI findings.…”

A Thyroid Hormone Receptor α Gene Mutation (P398H) Is Associated with Visceral Adiposity and Impaired Catecholamine-stimulated Lipolysis in Mice

“…Catecholamines bind at least five subtypes of adrenergic receptors (␣1, ␣2, ␤1, ␤2, and ␤3) that are expressed in fat cells and are coupled with the adenylylcyclase system to activate (via ␤ receptors) or inhibit (via ␣2 receptor) the cAMPactivated hormone-sensitive lipase (HSL) 1 (5)(6)(7)(8)(9). Reduced catecholamine-stimulated lipolysis in hypothyroidism is thought to be due to a reduced number of ␤-adrenergic receptors (␤1 and ␤2) in fat cells (4, 10 -13), reduced interaction with G s , and enhanced G i protein interaction via ␣2-adrenergic receptorcoupled stimulation (14).…”

β-Adrenoceptor Blocker Carvedilol Provides Cardioprotection via an Adenosine-Dependent Mechanism in Ischemic Canine Hearts

“…3,4 Carvedilol decreases vascular resistance 3 and improves the pathophysiology of chronic heart failure. 5 This drug dilates both systemic and coronary vessels, 6 which is not a typical characteristic of ␤-blockers. Although this vasodilatory action may contribute to the beneficial effects of carvedilol in ischemic or nonischemic heart failure, 5 it may not be the primary mechanism of cardioprotection, because vasodilators are not always effective at protecting the heart.…”