Cardiovascular pharmacology of adrenergic and dopaminergic receptors: therapeutic significance in congestive heart failure.
This review discusses the localization of adrenergic- and dopaminergic-adrenoceptors within the cardiovascular system and describes the cardiovascular and renal changes produced following the activation of these receptors by appropriate agonists. Whereas the role of alpha- and beta-adrenergic agents in the treatment of heart failure is well recognized, recent studies with dopamine (DA)-receptor agonists indicate that they offer a novel approach in the therapy of congestive heart failure. DA-adrenoceptor agonists reduce afterload by causing vasodilation and promote sodium excretion via direct activation of DA1-adrenoceptors located on renal tubules. Fenoldopam is a selective DA1-adrenoceptor agonist found to be effective in heart failure. It reduces afterload by causing peripheral vasodilation and produces natriuresis and diuresis. Dopexamine is a DA1- and beta 2-adrenoceptor agonist, and its efficacy in heart failure is due to its ability to provide mild inotropic support and cause a reduction in afterload. Ibopamine is a prodrug that is converted into its active metabolite, epinine. This compound activates primarily DA1- and DA2-adrenoceptors. It is effective in heart failure, and the mechanism progresses via DA1- and DA2-adrenoceptor-mediated reduction in afterload. Agonists of DA2-adrenoceptors reduce afterload by decreasing the release of norepinephrine and by reducing the levels of renin-angiotensin-aldosterone system. Since both of these systems are active in heart failure, ibopamine offers a rational approach for therapy. The present review addresses the concept of pharmacologic intervention in adrenergic and dopaminergic influence in the cardiovascular and renal systems to produce changes that are desirable for the pharmacotherapy of congestive heart failure.
Lokhandwala
M F
MF
Department of Pharmacology, University of Houston, TX 77204-5515.
Hegde
S S
SS
D000322:Adrenergic Agonists / Q000627:therapeutic use*; D015259:Dopamine Agents / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*
D000322:Adrenergic Agonists; D015259:Dopamine Agents; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine