Influence of chloride ions on #alpha#_1-adrenoceptor mediated contraction and Ca~(2+) influx in rat caudal artery

摘要

The objective of the present investigation was to compare and contrast the effects of 8-bromoguanosine 3’:5’-cyclic monophosphate (8-Bromo-cyclic GMP), an analogue of guanosine 3’:5’-cyclic monophosphate, felodipine, a dihydropyridine Ca~(2+) channel antagonist, and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a putative chloride channel antagonist on #alpha#_-adrenoceptor mediated contraction and Ca~(2+) influx in rat caudal artery, in normal physiological salt solution and in chloride-free solution. Isometric contractions and ~(45)CA~(2+) influx were measured in isolated rat caudal arterial rings. Phenylephrine induced concentration-dependent contractions were inhibited by 8-Bromo-cyclic GMP (10 #mu#M), felodipine (10 nM) and NPPB (3.0 #mu#M). Removal of chloride ions also impaired phenylephrine-induced contractions. In chloride-free buffer, phenylephrine-induced contractions were partially inhibited by the presence of 8-Bromo-cGMP or felodipine, while NPPB HAD NO EFFECT. Phenylephrine induced ~(45)Ca~(2+) influx was inhibited by the presence of 8-Bromo-cyclic GMP, felodipine and NPPB. Moreover, removal of chloride ions also inhibited phenylephrine-induced ~(45)Ca~(2+) influx. The results of our study demonstrate that in the rat caudal artery the inhibitory effects of 8-Bromo-cyclic GMP, felodipine and NPPB, are mediated through a reduction of Ca~(2+) influx. In addition, chloride ions, in part, play a role in #alpha#_1-adrenoceptor-mediated Ca~(2+) influx. However, the influence of removal of chloride ions on phenylephrine stimulated contraction is limited. Moreover, 8-Bromo-cyclic GMP and felodipine, but not NPBB, impair p