Release of Noradrenaline in Myocardial Ischemia—Importance of Local Inactivation by Neuronal and Extraneuronal Mechanisms

Abstract

Summary: The ability of l-dopa and dopamine to modulate renal vascular responses to norepinephrine (NE, 50–150 ng) was examined in isolated Tyrode-perfused kidneys from male Sprague-Dawley rats. Renal pressor responses to bolus injections of NE were constant during saline infusion. In contrast, l-dopa (15 μg/min and 75 μg/ min) and dopamine (15 μg/min) infusions that did not alter baseline perfusion pressure increased pressor responses to NE significantly. Concomitant infusion of the aromatic 1-amino-acid decarboxylase inhibitor carbidopa (20 μg/min) suppressed the ability of l-dopa (75 μg/min) but not dopamine to enhance renal pressor responses to NE. The pressor potentiation of NE did not appear to be the result of a general musculotropic effect or altered alpha-1 adrenoreceptor activity since increased vasoconstrictor responses to phenylephrine (PE) and serotonin (5-HT) were not observed. Infusions of cocaine (15 μg/ min) enhanced the renal pressor effects of NE but not PE in similar fashion to 1-dopa and dopamine. In the presence of cocaine, l-dopa did not potentiate NE constriction further. These results suggest that endogenous or exogenous dopamine in the kidney may affect neuronal NE uptake to enhance its renal vascular effects.