Comparison of cardiovascular effects of SGB-1534 and prazosin, selective alpha 1-adrenoceptor antagonists, in anesthetized dogs

The cardiovascular effects of a novel antihypertensive agent, SGB-1534, and its alpha 1-adrenoceptor antagonism in the renal vasculature were investigated in anesthetized dogs and compared with those of prazosin. The doses of SGB-1534 (1-100 micrograms/kg) and prazosin (3-300 micrograms/kg) were increased by a factor of about 3 and given i.v. in a cumulative way. SGB-1534 produced dose-dependent decreases in systemic (systolic, mean and diastolic) blood pressure (SBP), left ventricular (LV) systolic and end-diastolic pressure, and femoral vascular resistance, accompanied by no changes in heart rate (HR), LVdP/dt max and pressure-rate product. Femoral blood flow tended to increase, but the change was not significant. Renal blood flow and the vascular resistance remained virtually unchanged. Similar results were obtained with prazosin for the cardiovascular parameters tested except diastolic SBP and femoral vascular resistance, in which no significant changes occurred. SGB-1534 and prazosin dose-dependently attenuated renal vasoconstrictor responses to a relatively selective alpha 1-adrenoceptor agonist, phenylephrine (3 or 10 micrograms) given into the renal artery. When the doses that attenuated the vasoconstrictor response to phenylephrine by 50% were compared on a weight basis, alpha 1-adrenoceptor antagonistic activity of SGB-1534 was approximately 25 times more potent than that of prazosin in the renal vasculature of dogs. Both alpha 1-adrenoceptor antagonists showed a significant positive correlation between the systemic hypotensive effects and the alpha 1-adrenoceptor antagonism in the renal vasculature. Thus, it seems that SGB-1534, like prazosin, has a balanced effect decreasing afterload as well as preload and that the hypotension is mainly due to the alpha 1-adrenoceptor antagonism in the peripheral vasculatures.