Effects of an antihypertensive vasodilator, pinacidil, on regional blood flow in conscious spontaneously hypertensive rats.
Using a radioactive microsphere method, the effects of hydralazine and a new antihypertensive vasodilator, pinacidil, on systemic and regional hemodynamics were examined and compared in conscious Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). A single intravenous administration of pinacidil decreased mean blood pressure in a dose dependent fashion (0.03-0.3 mg/kg), and the peak effect was observed within a few minutes after administration. The onset of the hypotensive action of hydralazine was relatively slow compared to that of pinacidil, and its peak effect appeared 5-10 min after administration. There was no difference between WKY and SHR in the time course of blood pressure change, but the pressure reduction in WKY was less than that in SHR. We observed regional hemodynamic differences between the normotensive rats and the hypertensive rats. The flow rates in the kidney, spleen, gastrointestinal tract and skin of SHR were significantly lower than those of WKY. The intravenous infusion of pinacidil at a rate of 0.06 mg/kg/min increased cardiac output and heart rate, and selectively increased flow rates in organs with low flow rates compared to normotensive controls except for the spleen. Thus, pinacidil reduced total peripheral resistance of SHR to levels of WKY and normalized hemodynamic abnormalities in SHR. The regional hemodynamic action of pinacidil in SHR was not qualitatively different from that of hydralazine except in a few organs.
Kimura
S
S
Department of Pharmacology, Kagawa Medical School, Japan.
Fujioka
S
S
Fukui
K
K
Tamaki
T
T
Iwao
H
H
Abe
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology; D008863:Microspheres; D020110:Pinacidil; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D006146:Guanidines; D014665:Vasodilator Agents; D006830:Hydralazine; D020110:Pinacidil