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 prodr ug, docarpamine (200 mu g/kg), on mean arterial pressure (MAP) and heart ra te (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). I n WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then re turned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP a nd HR gradually increased, reaching a nadir 20 min after injection. Five mi n 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-i nduced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the DI-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V-1 (n=3) receptor blockade also abrogated the effects of docarparmine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpami ne are mediated by D-1-like receptors. In WKY rats, the pressor and tachyca rdiac responses are caused by an interaction among D-1-like, alpha-adrenerg ic, and V-1 receptors.