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.
DeFeo
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TT
Cardiovascular Division, Charles A. Dana Research Institute, Boston, MA.
Morgan
K G
KG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002335:Carnivora / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology*; D005289:Ferrets / Q000502:physiology*; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*
D005576:Colforsin; D006830:Hydralazine; D009543:Nifedipine; D002118:Calcium