Effects of dopamine, N-N-di-n-propyl dopamine, and (R)- and (S)-sulpiride on guinea pig blood pressure.

Effects of intravenous injections of dopamine (DA) and N-N-di-n-propyl dopamine (DPDA) on mean arterial pressure (MAP) and heart rate (HR) were studied in urethane-anesthetized guinea pigs. DA and DPDA produced dose-related reductions in MAP. DA produced a biphasic change in HR, an initial decrease followed by an increase, while DPDA produced only a decrease in HR. Phentolamine and hexamethonium did not affect the depressor effects of DA, but virtually abolished the depressor effects of DPDA. Thus, DA appears to lower MAP primarily by direct vasodilation; whereas DPDA acts predominantly by inhibiting the sympathetic nervous system. Hexamethonium prevented the bradycardia induced by DA and DPDA, but had no effect on the DA-induced tachycardia. (R)- and (S)-sulpiride produced hypotensive effects of short duration that were due to their weak alpha-adrenergic blocking activity. In addition, the (R) enantiomer produced a secondary pressor effect that was abolished by phentolamine and hexamethonium. (R)-sulpiride potentiated pressor effects of the ganglionic stimulant 1-1-dimethyl-4-phenylpiperazinium iodide (DMPP), suggesting that it facilitated sympathetic nerve activity. This study demonstrates that guinea pig blood pressure can be used to differentiate between the neuronal and vascular origins of hypotension produced by DA agonists. The use of (R)- and (S)-sulpiride for further localizing the actions of DA and DPDA is complicated by their alpha-adrenergic blocking activity and by an apparent facilitatory effect of (R)-sulpiride on sympathetic nerve transmission.