Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model

Life Sci. 1993;52(8):717-24. doi: 10.1016/0024-3205(93)90233-s.


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.

MeSH terms

  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Endothelins / antagonists & inhibitors*
  • Endothelium, Vascular / drug effects
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • In Vitro Techniques
  • Male
  • Models, Genetic
  • Molecular Sequence Data
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Swine


  • Antihypertensive Agents
  • Endothelins
  • Peptides, Cyclic
  • cyclo(Trp-Asp-Pro-Val-Leu)