Dopamine: a role in the pathogenesis and treatment of hypertension.
The catecholamine dopamine (DA), activates two distinct classes of DA-specific receptors in the cardiovascular system and kidney--each capable of influencing systemic blood pressure. D1 receptors on vascular smooth muscle cells mediate vasodilation, while on renal tubular cells they modulate sodium excretion. D2 receptors on pre-synaptic nerve terminals influence noradrenaline release and, consequently, heart rate and vascular resistance. Activation of both, by low dose DA lowers blood pressure. While DA also binds to alpha- and beta-adrenoceptors, selective agonists at both DA receptor classes have been studied in the treatment of hypertension. An unfavourable side-effect profile (largely nausea and orthostasis) have precluded wide use of D2 agonists. In contrast, the D1 selective agonist fenoldopam has been licensed for the parenteral treatment of severe hypertension. Apart from inducing systemic vasodilation it induces a diuresis and natriuresis, enhanced renal blood flow, and a small increment in glomerular filtration rate. Evidence is emerging that abnormalities in DA production, or in signal transduction of the D1 receptor in renal proximal tubules, may result in salt retention and high blood pressure in some humans and in several animal models of hypertension.
Murphy
M B
MB
Department of Pharmacology and Therapeutics, National University of Ireland, Cork.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D004298:Dopamine