Immediate Hemodynamic Changes Produced by Urapidil in Normotensive and Spontaneously Hypertensive Rats

The immediate effects on regional and systemic hemodynamics of urapidil (1 mg/kg IV), a recently synthesized vasodilator with a possible combined central and peripheral action, were studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Maximal decrease in mean arterial pressure was achieved within the first minute after injection (154 +/- 4 vs 113 +/- 6 mm Hg in SHR and 111 +/- 4 vs 82 +/- 4 mm Hg in WKY, p less than 0.01). This effect was accompanied by a transient (10 min) significant increase in heart rate in both strains. There was a significant fall in total peripheral resistance (0.43 +/- 0.02 vs 0.30 +/- 0.02 U/kg in WKY and 0.62 +/- 0.03 vs 0.43 +/- 0.03 U/kg in SHR, p less than 0.01) and rise in cardiac index 15 min after drug injection (371 +/- 9 vs 425 +/- 12 ml/min/kg in WKY and 395 +/- 8 vs 432 +/- 112 ml/min/kg in SHR, p less than 0.01). Organ vascular resistance decreased significantly in all the organs of /KY and most of the organs of SHR rats. However, a significant increase in blood flow was observed only in skeletal muscle. The data indicate that urapidil is a potent hypotensive agent. The pressure fall is mediated through a decreased total peripheral resistance that is distributed through all circulations. The increased cardiac output and heart rate are most likely reflexly induced.