Dual effects of endothelin-1 on extracellular acidification by A7r5 smooth muscle cells

The effect of endothelin-1 on metabolic activity of A7r5 rat aortic smooth muscle cells was studied. Endothelin-1 (pEC(50) 7.5) elicited an increase in the rate of extracellular medium acidification of the A7r5 cells. The ETA receptor antagonist BQ-123 blocked the endothelin-1 effect completely (pA(2) 7.6). Ca2+ channel blockers affected the endothelin-1 induced response in different ways: diltiazem and nifedipine partially blocked the endothelin-1 induced response, whereas verapamil did not influence this endothelin-1 induced effect. However, upon removal of verapamil an endothelin-1 dependent rise in extracellular acidification occurred, apparently reflecting the lifting of the verapamil blockade of an endothelin-1 induced process. Thus, this study shows that the complex integrated cellular responses upon ET-1 receptor activation are reflected in metabolic activity.