title: Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model.
abstract: A newly synthesized ET(A)-selective antagonist, BQ-123, was examined with respect to its anti-endothelin(ET) action in vitro and in vivo and its effect on blood pressure in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). In isolated porcine coronary arteries, BQ-123 (0.07 microM to 6.0 microM) shifted the concentration-response curve for ET-1 to the right without affecting the maximal response of ET-1, its pA2 value being 7.35. Intravenous infusion of BQ-123 at a rate of 1.2 and 30 mg/kg/hr produced a significant decrease in blood pressure in 20- to 29-week-old SHRSP, but did not alter blood pressure in 13- to 16-week-old WKY or in 18- to 19-week-old and 40-week-old SHR. The hypotensive effect of BQ-123 depended on the pretreatment blood pressure level. These results suggest that ET-1 is involved in part in the maintenance of high blood pressure in malignant hypertension, as exemplified by SHRSP.
authors.affiliation: New Drug Discovery Research Laboratories, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishikibe
authors.forename: S
authors.initials: S
authors.lastname: Tsuchida
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Fukuroda
authors.forename: K
authors.initials: K
authors.lastname: Shimamoto
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
authors.forename: F
authors.initials: F
authors.lastname: Ikemoto
mesh_terms: D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D016232:Endothelins / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013552:Swine
chemical_list: D000959:Antihypertensive Agents; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)