Effects of putative K+ channel activator BRL-34915 on arterial contraction and 86Rb efflux
Cox, R.H.
Journal of Pharmacology and Experimental Therapeutics 252(1): 51-59
1990
ISSN/ISBN: 0022-3565 PMID: 2299602 Document Number: 355348
Segments of thoracic aorta, mesenteric and tail arteries from male Wistar rats were used for the determination of isometric relaxation responses to BRL-34915 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.