Comparative central and peripheral antihypertensive mechanisms of urapidil and prazosin

The central effects of urapidil were investigated in conscious rats with sinoaortic denervation. Intraventricular urapidil administration (40 to 100 micrograms) produced a transient depressor response followed by a pressor response coupled with tachycardia. In comparison, intraventricular prazosin administration (2.5 to 5.0 micrograms) produced only a prolonged depressor effect. The effect of intravenously administered urapidil (3 mg/kg) on arterial pressure, heart rate, and mesenteric, renal, and hindquarter resistances was then compared with that of prazosin (0.5 mg/kg) in conscious rats with sinoaortic denervation, instrumented with pulsed Doppler flow probes. Both agents caused similar significant decreases in arterial pressure and vascular resistances, but urapidil decreased renal resistance significantly more than did prazosin. Prazosin increased heart rate, whereas no change was found with urapidil. Prazosin blocked the pressor and regional constrictor effects of intravenously administered norepinephrine more effectively than urapidil.