Mechanisms of hydralazine induced vasodilation in rabbit aorta and pulmonary artery

1 The directly acting vasodilator hydralazine has been proposed to act at a n intracellular site in vascular smooth muscle to inhibit Ca2+ release. 2 This study investigated the mechanism of action of hydralazine on rabbit aorta and pulmonary artery by comparing its effects on the tension generate d by intact and beta -escin permeabilized vessels and on the cytoplasmic Ca 2+ concentration, membrane potential and K+ currents of isolated vascular s mooth muscle cells. 3 Hydralazine relaxed pulmonary artery and aorta with similar potency. It w as equally effective. at inhibiting phasic and tonic contractions evoked by phenylephrine in intact vessels and contractions evoked by inositol 1,4,5 trisphosphate (IP3) in permeabilized vessels. 4 Hydralazine inhibited the contraction of permeabilized vessels and the in crease in smooth muscle cell Ca2+ concentration evoked by caffeine with sim ilar concentration dependence, but with lower potency than its effect on IP 3 contractions. 5 Hydralazine had no effect on the relationship between Ca2+ concentration and force generation in permeabilized vessels, but it slowed the rate at wh ich maximal force was developed before, but not after, destroying sarcoplas mic reticulum function with the calcium ionophore, ionomycin. 6 Hydralazine had no effect on membrane potential or the amplitudes of K+ c urrents recorded from isolated smooth muscle cells over the concentration r ange causing relaxation of intact vessels. 7 The results suggest that the main action of hydralazine is to inhibit the IP3-induced release of Ca2+ from the sarcoplasmic reticulum in vascular sm ooth muscle cells.