Pharmacological Properties

Cardiovascular Effects The cardiovascular effects of DA are mediated by several distinct types of receptors that vary in their affinity for DA. At low concentrations, the primary interaction of DA is with vascular D1 receptors, especially in the renal, mesenteric, and coronary beds; this interaction leads to smooth muscle vasodilation (via the Gs-adenylyl cyclase-cAMP pathway). Infusion of low doses of DA causes an increase in glomerular filtration rate, renal blood flow, and Na+ excretion. Activation of D1 receptors on renal tubular cells decreases sodium transport by cAMP-dependent and cAMP-independent mechanisms. Increasing cAMP production in the proximal tubular cells and the medullary part of the thick ascending limb of the loop of Henle inhibits the Na+-H+ exchanger and the Na+,K+-ATPase. Renal tubular actions of DA that cause natriuresis may be augmented by the increase in renal blood flow and in glomerular filtration rate that follow its administration. The resulting increase in hydrostatic pressure in the peritubular capillaries and reduction in oncotic pressure may contribute to diminished Na+ reabsorption by the proximal tubular cells. Thus, DA has pharmacologically appropriate effects in the management of states of low cardiac output associated with compromised renal function, such as severe congestive heart failure.

At higher concentrations, DA acts on cardiac receptors to produce a positive inotropic effect. DA also causes the release of NE from nerve terminals, which contributes to its effects on the heart. DA usually increases systolic blood pressure and pulse pressure and either has no effect on diastolic blood pressure or increases it slightly. Total peripheral resistance usually is unchanged when low or intermediate doses of DA are given, probably because of reduced regional arterial resistance in some vascular beds (e.g., mesenteric and renal) with minor increases in others. At high concentrations, DA activates vascular a1 receptors, leading to more general vasoconstriction.

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