The α1-adrenoceptor antagonistic effect of SGB-1534, a novel phenylpiperazine derivative, was examined in the renal vascular bed of pentobarbital-anesthetized dogs. Renal nerve stimulation (RNS, 1 ms duration, 2,3 and 4 Hz) or intrarenal bolus injection of methoxamine (0.5, 1 and 2 μg/kg) or guanabenz (1, 3 and 10 μg/kg) produced a frequency- or dose-dependent decrease in renal blood flow (RBF). Both the RBF responses to RNS and methoxamine were inhibited dose dependently by an intrarenal infusion of SGB-1534 (1-30 ng/kg per min) or prazosin (30-300 ng/kg per min). When the equipotent inhibitory doses of the antagonists were compared, the antagonistic potency of SGB-1534 on the RBF responses evoked by RNS and methoxamine was about 30 times greater than that of prazosin. Prazosin also attenuated the RBF response to guanabenz, whereas SGB-1534 had little effect. These results suggest that SGB-1534 has a selective α1-adrenoceptor-blocking property and that it inhibits neurally mediated renal vasoconstriction. The α1-adrenaceptor antagonistic potency and selectivity of SGB-1534 may be greater than that of prazosin.
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