Reduced verapamil inhibition of endothelin-1-constricted rabbit basilar artery due to enhanced non L-type Ca2+-channel-dependent constriction

Abstract

This study tested whether (1) L-type Ca²⁺ channel blockade and extracellular Ca²⁺ 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 Ca²⁺ channel blockade resulted from enhanced non L-type Ca²⁺-channel-dependent constriction. Pretreatment of rabbit basilar artery in vitro with 1 μM verapamil, an L-type Ca²⁺ 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. Ni²⁺ (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 Ca²⁺ removal prior to 10, 30, and 100 nM endothelin-1 also inhibited the endothelin-1 constrictions to smaller magnitudes than Ca²⁺ removal during the plateau endothelin-1 constrictions. These results suggest that the reduced inhibition of the endothelin-1 constriction following pretreatment with L-type Ca²⁺ channel blocker or Ca²⁺-free solution, as compared to addition of these agents during the endothelin-1 constriction, is the result of non L-type Ca²⁺ channel opening and enhanced Ca²⁺-independent constriction, respectively.