Inhibition of calcium influx and tonic response to K+ of intestinal smooth muscle by hydralazine.

Abstract

1. Evidence concerning the mechanism of the inhibition of contraction caused by hydralazine has been sought in ileal longitudinal muscle and taenia coli of guinea-pig. Hydralazine (10(-3)-3 x 10(-3) M) markedly 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 threshold 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 caused 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 method during the K+ induced tonic response in ileal muscle; however, it did not affect the Ca2+ efflux. 4. In ileal muscle fibres treated with Triton-X-100, in which the Ca2+ release sites are destroyed, 10(-3) M hydralazine 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 may result mainly from the interference of calcium permeability at the cell membrane in ileal muscle. There is the possibility that hydralazine of higher concentrations may have a minor action on the contractile system.