Dopamine receptors and hypertension. Physiologic and pharmacologic implications

The endogenous catecholamine dopamine lowers blood pressure by acting on two receptor subtypes: dopamine 1 and dopamine 2. Dopamine 1 receptors subserve vasodilation, especially in the renal, coronary, mesenteric, and cerebral vascular beds. Dopamine 2 receptors have been located at the endings of postganglionic sympathetic nerves and, when activated, inhibit norepinephrine release. Inhibition of emesis and inhibition of prolactin release also appear to be dopamine 2-mediated phenomena. The receptor subtypes have been classified by differences in chemical structure of agonists and by specific antagonists. Dopamine also acts on beta 1 receptors to stimulate the heart and alpha 1 and alpha 2 receptors to cause vasoconstriction. Alpha adrenergic activity and lack of oral availability limit the use of dopamine in the treatment of hypertension. However, studies with the selective dopamine 1 agonist, fenoldopam, and dopamine 2 agonists such as LY 141865 and bromocriptine, indicate that agonists of both receptor subtypes can lower blood pressure in experimental animals and in hypertensive patients. Initial use of dopamine agonists in the treatment of hypertension and its possible involvement in the etiology and maintenance of hypertension are discussed.