The mechanism of tension inhibitory effects on histamine and caffeine-induced responses by hydralazine were studied in the ileal longitudinal muscle and taenia coli of the guinea-pig. Hydralazine, 10(-4) to 3 x 10(-3) M, inhibited both the tonic response and the increase in Ca uptake by the lanthanum (La) method evoked by histamine (10(-5) M) without affect on Ca efflux, with smaller effects on the phasic response in ileal muscle. 2. Hydralazine suppressed caffeine- and IP3-induced contractions after loading with Ca2+ into the storage sites in saponin-treated fibers. However, hydralazine suppressed the caffeine- and IP3-induced contractions in the skinned fibers relatively less than both the transient response to caffeine and phasic response to histamine in intact muscles, respectively. 3. It is probable that hydralazine reduces the tonic response to histamine mainly by inhibiting Ca2+ influx through receptor operated Ca2+ channels in the ileum. In addition, hydralazine also decreases caffeine- or IP3-induced Ca2+ release from storage sites.
