Signal transduction pathways in constriction of the basilar artery in vivo.
We examined effects of a putative myosin light chain kinase inhibitor in the cerebral circulation in vivo. In anesthetized rats, diameter of basilar arteries was measured through a cranial window (control, 232 +/- 10 microns, mean +/- SEM). Vessel diameter was measured during topical application of agonists and antagonists. ML-7, which has been reported to compete with adenosine triphosphate for binding to the catalytic site on myosin light chain kinase, attenuated vasoconstriction in response to prostaglandin F2 alpha (10(-6) M; -22 +/- 1% before versus -14 +/- 1% and -3 +/- 2% during ML-7, 10(-7) and 10(-6) M, respectively; p less than 0.05). ML-7 (10(-6) M) did not affect baseline diameter. Responses to serotonin (10(-8) M) and phorbol 12,13-dibutyrate (10(-8) M) were not attenuated by ML-7. Thus, constriction of the basilar artery induced by prostaglandin F2 alpha in vivo is attenuated by an inhibitor of myosin light chain kinase.
Murray
M A
MA
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Faraci
F M
FM
Heistad
D D
DD
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D014677:Pharmaceutical Vehicles; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D001381:Azepines; D009281:Naphthalenes; D014677:Pharmaceutical Vehicles; C070571:ML 7; D015237:Dinoprost; D009219:Myosin-Light-Chain Kinase; D004121:Dimethyl Sulfoxide