SCIENCE@home

Y-27152, a long-acting K+ channel opener with less tachycardia: antihypertensive effects in hypertensive rats and dogs in conscious state.

Tohru Nakajima,T. Shinohara,O. Yaoka,A. Fukunari,K. Shinagawa,Kazumi Aoki,A. Katoh,T. Yamanaka,Michihide Setoguchi,Tetsuya Tahara

Published 1992 in Journal of Pharmacology and Experimental Therapeutics

ABSTRACT

(+)-(3S,4R)-4-(N-Acetyl-N-benzyloxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl- 2H-1-benzopyran-3-ol (Y-27152) is a new K+ channel opener with a long duration of action and less tachycardia. In this study, Y-27152 was compared with a K+ channel opener lemakalim and a Ca++ channel blocker nifedipine for antihypertensive activity in conscious spontaneously hypertensive rats (SHR) and two-kidney, one-clip renal hypertensive dogs (RHD). In conscious SHR, Y-27152 (0.1-1 mg/kg, p.o.) produced long-lasting dose-related decreases in systolic blood pressure. At 1 mg/kg, the maximum response occurred 5 to 7 hr after dosing, and 24 hr later, the pressure was still significantly reduced. Heart rate was not changed by these doses of Y-27152, whereas equihypotensive doses of lemakalim or nifedipine were strongly tachycardic. The cardiovascular effects of Y-27152 were antagonized by glibenclamide (20 mg/kg, i.v.). In conscious unrestrained RHD, Y-27152 at doses of 0.01, 0.03 and 0.1 mg/kg lowered blood pressure with a slow onset and long duration of action and had only a minimal effect on heart rate, whereas both lemakalim and nifedipine reduced blood pressure and markedly increased heart rate. No tolerance to the antihypertensive effect of Y-27152 (0.1 mg/kg) occurred during an 8-week repeated daily dosing to RHD and plasma renin activity, and aldosterone levels were not elevated during this period. In rat aortic rings contracted with 20 mM KCl, Y-27152 did not modify the tension; however, its desbenzyl form (Y-26763) produced vasorelaxation, and this effect was antagonized competitively by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-29 of 29 references · Page 1 of 1

CITED BY

Showing 1-22 of 22 citing papers · Page 1 of 1