INHIBITION OF CALCIUM INFLUX AND TONIC RESPONSE TO K-MUSCLE BY HYDRALAZINE( OF INTESTINAL SMOOTH)

1 Evidence concerning the mechanism of the inhibition of contraction c aused by hydralazine has been sought in ileal longitudinal muscle and taenia coli of guinea-pig. Hydralazine (10(-3) - 3 x 10(-3) M) markedl y inhibited K+ (60 mM) induced tonic response with smaller effects on the phasic response in the ileal muscle. However, 10(-2) M hydralazine completely abolished both responses. 2 Hydralazine increased the thre shold for Ca2+ induced contraction in Ca2+ free, K+ depolarized taenia coli and reduced the maximal response size. A low concentration (3 x 10(-10) M) of nifedipine, an L-type Ca2+ channel blocker, further caus ed a parallel shift to the right in the presence of hydralazine in the concentration-response curves obtained with Ca2+ 3 Hydralazine caused a significant decrease in Ca2+ uptake measured by the lanthanum metho d during the K+ induced tonic response in ileal muscle; however, it di d not affect the Ca2+ efflux. 4 In ileal muscle fibres treated with Tr iton-X-100, in which the Ca2+ release sites are destroyed, 10(-3) M hy dralazine had no effect on the contractions induced by 10(-5) M Ca2+; however, hydralazine at a higher concentration (10(-2) M) had a slight inhibitory effect on the contraction. 5 The present finding indicates that the inhibitory action on contractions produced by hydralazine ma y result mainly from the interference of calcium permeability at the c ell membrane in ileal muscle. There is the possibility that hydralazin e of higher concentrations may have a minor action on the contractile system.