Reduced verapamil inhibition of endothelin-1-constricted rabbit basilar artery due to enhanced non L-type Ca(2+)-channel-dependent constriction.
This study tested whether (1) L-type Ca(2+) channel blockade and extracellular Ca(2+) removal prior to endothelin-1, as compared to during the endothelin-1 constriction, resulted in lesser inhibition, and (2) the reduced inhibition due to prior L-type Ca(2+) channel blockade resulted from enhanced non L-type Ca(2+)-channel-dependent constriction. Pretreatment of rabbit basilar artery in vitro with 1 microM verapamil, an L-type Ca(2+) channel blocker, inhibited 3, 10, 30, and 100 nM endothelin-1 constrictions to a lesser extent than verapamil addition during the plateau endothelin-1 constriction. Ni(2+) (0.03 and 0.1 mM), a nonselective cation channel blocker, relaxed the plateau endothelin-1 constrictions in vessels pretreated with verapamil to greater magnitudes than vessels unexposed to verapamil. Extracellular Ca(2+) removal prior to 10, 30, and 100 nM endothelin-1 also inhibited the endothelin-1 constrictions to smaller magnitudes than Ca(2+) removal during the plateau endothelin-1 constrictions. These results suggest that the reduced inhibition of the endothelin-1 constriction following pretreatment with L-type Ca(2+) channel blocker or Ca(2+)-free solution, as compared to addition of these agents during the endothelin-1 constriction, is the result of non L-type Ca(2+) channel opening and enhanced Ca(2+)-independent constriction, respectively.
Zuccarello
M
M
Surgical Service, Veterans Affairs Medical Center, Department of Neurosurgery, University of Cincinnati College of Medicine, PO Box 670515, Cincinnati, OH 45267-0515, USA.
Lee
B H
BH
Rapoport
R M
RM
D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009532:Nickel / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D011189:Potassium Chloride; D009532:Nickel; D014700:Verapamil; D002118:Calcium