Calcium-force coupling mechanisms during vasodilator-induced relaxation of ferret aorta.

1. The effects of three vasodilators, nifedipine, hydralazine and forskolin, were determined on isometric force and intracellular ionized calcium concentration ([Ca2+]i) as indicated by aequorin in ferret aorta. Three types of contraction were studied: the intrinsic tone induced by warming from 22 to 37 degrees C; the contraction to the phorbol ester 12-deoxyphorbol-13-isobutyrate-20-acetate (DPBA); and the contraction to potassium depolarization. 2. On warming there was no significant steady-state change in [Ca2+], even though 5.7 +/- 0.7 mN of tone developed. During potassium depolarization, [Ca2+]i rose to a sustained plateau while DPBA caused no significant rise in [Ca2+]i. 3. Nifedipine and hydralazine inhibited intrinsic tone while causing an associated decrease in [Ca2+]i; but in the presence of forskolin, a similar inhibition of tone was accompanied by no significant decrease in [Ca2+]i. 4. Nifedipine and hydralazine prolonged the characteristic lag phase before force development in response to DPBA but did not cause a significant change in contraction amplitude. In contrast, forskolin caused an essentially total inhibition of the contraction. 5. During potassium depolarization, all three vasodilators caused significant decreases in [Ca2+]i coincident with decreases in steady-state force. Calcium-force curves were constructed by plotting the calibrated aequorin light signal against the resulting force. The control calcium-force curve was not shifted by nifedipine or hydralazine but was significantly shifted to the right by forskolin.