SENSITIVITY TO PROTEIN-KINASE-C INHIBITORS OF NICARDIPINE-INSENSITIVECOMPONENT OF HIGH K-PIG AORTA( CONTRACTURE IN RAT AND GUINEA)

1 In the rat and guinea-pig aorta, we observed that the contraction to hypertonically-added K+, unlike the isotonic K+-induced contraction, was only partially sensitive to nicardipine (0.1, 1 and 10 mu M), an L -type Ca2+ channel blocker and occurred in Ca2+-free medium containing 50 mu M EGTA. We have characterized this nicarpidine-insensitive hype rtonically-added K+ contraction. 2 The contraction induced by an equi- osmolar concentration of mannitol was similar in size to that evoked b y hypertonically-added K+. 3 When the tissue was depleted of its inter nal Ca2+ stores with various agents such as phenylephrine (10 mu M), c yclopiazonic acid (30 mu M), thapsigargin (1 mu M) or ryanodine (30 mu M), or by incubation in Ca2+-free medium over 30 min, little effect w as observed on the high K+ contracture in the presence of L-type Ca2channel blockade. 4 Phentolamine (10 mu M) or indomethacin (10 mu M) d id not reduce the contraction induced by high K+. 5 Application of a p rotein kinase C inhibitor, H7 (10, 30 and 100 mu M) or calphostin C (1 mu M), reduced the high K+ contraction but not that caused by an equi -osmolar concentration of mannitol. 6 The data suggest that hypertonic K+-induced contraction differs from that caused by hypertonicity or d epolarization per se and invokes membrane enzyme activation.