title: Effects of a novel alpha 1-adrenoceptor antagonist, SGB-1534, on adrenergically induced renal vasoconstriction in dogs.
abstract: The alpha 1-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 micrograms/kg) or guanabenz (1, 3 and 10 micrograms/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 alpha 1-adrenoceptor-blocking property and that it inhibits neurally mediated renal vasoconstriction. The alpha 1-adrenoceptor antagonistic potency and selectivity of SGB-1534 may be greater than that of prazosin.
authors.affiliation: Department of Pharmacology, Tohoku University, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Chiba
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Hisa
authors.forename: M
authors.initials: M
authors.lastname: Suzuki-Kusaba
authors.forename: S
authors.initials: S
authors.lastname: Satoh
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006143:Guanabenz / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C042712:SGB 1534; D006143:Guanabenz; D008729:Methoxamine; D011224:Prazosin