Effects of potassium channel activators on isolated cerebral arteries of large and small diameter in the cat.
The smooth-muscle relaxant action of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels in cerebral arteries of large diameter has been confirmed in a number of in vitro studies, but there is still debate about the presence of KATP channels in small cerebral arteries. In the present study, the authors compare the effects of cromakalim and bimakalim, two putative KATP channel activators, in different parts of the feline isolated middle cerebral artery (MCA) designated proximal, intermediate, and distal. The latter corresponds to those small pial arteries that are usually studied in vivo. In ring segments precontracted with 10(-5) M of uridine-5-triphosphate (UTP), both cromakalim and bimakalim induced concentration-related relaxation, with bimakalim being more potent than cromakalim, and no significant differences noted among segments obtained from the different regions of the MCA. In vessels precontracted by adding 30 mM KCl the potency of cromakalim and bimakalim was reduced compared with that obtained after UTP precontraction. In the presence of 10(-6) M glibenclamide, an antagonist of KATP channel activators, the concentration-effect curve to bimakalim was shifted to the right in the proximal and distal MCA, indicating a similar route of action for bimakalim and cromakalim in these arteries. The present study therefore indicates the presence of KATP channels in isolated small cerebral arteries according to results obtained in vivo. Activators of KATP channesl may prove helpful in the treatment of vasospasm, which may occur in large and small cerebral arteries after subarachnoid hemorrhage.
Schilling
L
L
Department of Physiology, University of Munich, Germany.
Parsons
A A
AA
Wahl
M
M
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects*; D019806:Cromakalim; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D004095:Dihydropyridines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C061050:bimakalim; D005905:Glyburide; D014544:Uridine Triphosphate