The effect of docarpamine, a dopamine pro-drug, on blood pressure and catecholamine levels in spontaneously hypertensive rats.

We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 microg/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). In WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then returned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP and HR gradually decreased, reaching a nadir 20 min after injection. Five min after docarpamine, plasma dopamine and 3,4-dihydroxy phenyl acetic (DOPAC) levels increased in both WKY rats (n=5) and SHRs (n=5). The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the D1-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V1 (n=3) receptor blockade also abrogated the effects of docarpamine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpamine are mediated by D1-like receptors. In WKY rats, the pressor and tachycardiac responses are caused by an interaction among D1-like, alpha-adrenergic, and V1 receptors.