Systemic and pulmonary vascular effects of selective dopamine receptor blockade and stimulation in lambs

Vascular dopamine (DA1) receptors may modulate circulatory hemodynamics in lambs. We evaluated resting dopaminergic tone in lambs by pharmacologically manipulating peripheral DA1 receptors with i.v. SCH 23390, (a highly selective, competitive DA1 receptor antagonist) and i.v. fenoldopam, (a highly selective DA1 receptor agonist) in unanesthetized lambs, instrumented for circulatory studies, while measuring the systemic and pulmonary vascular changes that the manipulations induced. We examined both the independent effects of DA1 receptor stimulation and blockade as well as the effects of the agonist and the antagonist infused together (competitive interaction). SCH 23390, infused at 2.5 micrograms/kg.min-1, caused significant increases in left atrial, systemic, and pulmonary artery pressure, as well as an increase in systemic vascular resistance and a decrease in heart rate. Fenoldopam, infused at the dose of 60 micrograms/kg.min-1 caused significant decreases in mean systemic artery pressure and systemic vascular resistance while increasing cardiac index and mean pulmonary artery pressure. SCH 23390 blunted the fenoldopam-induced effects. Our data suggest that dopaminergic influence may be active in the maintenance of resting hemodynamics of the lamb.