Mechanisms of hydralazine induced vasodilation in rabbit aorta and pulmonary artery

Abstract

1. The directly acting vasodilator hydralazine has been proposed to act at an 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 generated by intact and β-escin permeabilized vessels and on the cytoplasmic Ca2+ concentration, membrane potential and K+ currents of isolated vascular smooth muscle cells. 3. Hydralazine relaxed pulmonary artery and aorta with similar potency. It was 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 increase in smooth muscle cell Ca2+ concentration evoked by caffeine with similar concentration dependence, but with lower potency than its effect on IP3 contractions. 5. Hydralazine had no effect on the relationship between Ca2+ concentration and force generation in permeabilized vessels, but it slowed the rate at which maximal force was developed before, but not after, destroying sarcoplasmic reticulum function with the calcium ionophore, ionomycin. 6. Hydralazine had no effect on membrane potential or the amplitudes of K+ currents recorded from isolated smooth muscle cells over the concentration range 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 smooth muscle cells.