Calcium channel activation does not increase release of endothelial-derived relaxant factors (EDRF) in rat aorta although tonic release of EDRF may modulate calcium channel activity in smooth muscle.
We investigated whether Ca2+ channel activation by K+ or Bay K 8644 could cause release of endothelium-derived relaxant factor (EDRF) from rat aorta. Bay K 8644 (0.1-100 nM) did not relax rat aorta preparations partially contracted with phenylephrine, although acetylcholine caused large relaxations. Following partial K+-depolarization (12 or 15 mM), Bay K 8644 (10 nM-1 microM) contracted rat aorta preparations directly. Preparations were more sensitive to Bay K 8644 when stripped of the endothelium in 12 mM K+; concentration-effect curves were displaced to the left, and maximum responses were enhanced. In 15 mM K+, there was a leftward shift of the curves without change of maximal responses. However, Bay K 8644 (1 microM), did not increase the guanosine 3',5' cyclic-monophosphate (cGMP) content of rat aorta in the presence of endothelium, which is a function of EDRF release. Representatives (nifedipine, verapamil, cinnarizine) from different calcium antagonist subgroups had differential effects on contractions induced by Bay K 8644, and the effects of verapamil (1 and 10 microM) and lower concentrations of cinnarizine (1 microM) were reduced in the presence of endothelium. We propose that there is a tonic liberation of EDRF in rat aorta, which is unaffected by Ca2+ channel activation and which gives effects similar to a weak hyperpolarization of the smooth muscle cells. Consequently, Ca2+ channel activation and sensitivity to certain calcium-antagonists may be modified.