Calcium Dependence of Contractile Activation of Isolated Sheep Urethra II: Responses to Exogenous Noradrenaline

Isolated smooth muscle of sheep urethra responded to exogenous noradrenaline (NA) with a concentration-dependent contraction. After exposing the preparations for 30 min. to calcium-free medium, NA in a submaximal concentration was still able to produce a contractile response amounting to 36% of control value in calcium-containing solution. Readmission of calcium (administered cumulatively) restored the response in a concentration-related fashion to 85% (at 5 mM calcium) of control level. Nifedipine and verapamil failed to inhibit these graded calcium contractions in the presence of NA. Verapamil and diltiazem also failed to significantly prevent contraction induced by NA in a submaximum concentration, but nifedipine showed a concentration-dependent inhibitory effect, with a potency 1000 times lower than that observed on K+ (124 mM) induced contractions. In calcium-free medium, repeated applications of NA at 30 min. intervals, induced a progressive reduction in contractile amplitude. Nifedipine or verapamil did not affect the time course for recovery of NA-induced contraction when the preparations were returned to calcium containing medium, but the recovery was blocked almost completely by lanthanum. Furthermore, lanthanum abolished the remaining NA contraction in calcium-free medium. The results suggest that NA-induced contraction in isolated sheep urethra is dependent on both influx of extracellular calcium and on release of intracellular calcium. Calcium influx for contractile activation and refilling of intracellular stores seem to occur through membrane channels that can only partly be blocked with calcium antagonists.