Effects of putative K+ channel activator BRL-34915 on arterial contraction and 86Rb efflux

RH Cox

Bockus Research Institute, Graduate Hospital, Philadelphia, Pennsylvania.

Segments of thoracic aorta, mesenteric and tail arteries from male Wistar rats were used for the determination of isometric relaxation responses to BRL-34915 [chromakalin or (+/-)-6-cyano-3,4-dihydro-2,2- dimethyl-trans-4-(2-oxo-1-pyrrolidyl )-2H-benzo- [b]-pyran-3-ol] after contraction with half-maximal (ED50) values of norepinephrine or high K(+)-physiological salt solution. Contiguous segments were incubated in the presence of 86Rb and used for study of the effects of BRL-34915 on 86Rb efflux. BRL-34915 produced a dose-dependent relaxation of norepinephrine- or K(+)-induced active stress that was essentially complete (100%) in the aorta and mesenteric artery but only partial (30- 40%) in the tail artery. The ED50 value of BRL-34915 for relaxation responses was about 0.1 to 0.3 microM. BRL-34915 had no significant sustained effect on 86Rb efflux from the tail artery or mesenteric artery branches but produced a dose-dependent sustained increase in efflux from thoracic aorta and portal vein. Responses reached a peak effect in 2 to 4 min after exposure but subsequently declined over a slower time course. Efflux responses to BRL-34915 had peak values that averaged 100 to 150% above basal levels with an ED50 value of about 1 to 3 microM. This suggests a dissociation of the effects of BRL-34915 in relaxation and efflux experiments. Treatment with 30 microM BRL- 34915 decreased both the initial and sustained components of the subsequent 86Rb efflux response to 10 microM norepinephrine in both thoracic aorta and tail artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 252, Issue 1, pp. 51-59, 01/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics