Interaction of hydralazine and hydrazone derivatives with contractile mechanisms in rabbit aortic smooth muscle

The mechanism of action and relative potency of hydralazine (H) and two hydrazone derivatives were investigated using isolated rabbit aortic strips. H, hydralazine acetone hydrazone (HA) and hydralazine butanone hydrazone (HBH) relaxed established K ⁺ and norepinephrine (NE) contractures, and inhibited the development of contractures to these two agents on preincubation. H, HA and HBH increased the threshold to Ca ⁺⁺ and decreased the maximum tension responses during K ⁺-Ca ⁺⁺ contractures (HA>H, P<.05; HBH>H P<.01). The Ca ⁺⁺-dependent and Ca ⁺⁺-independent components of NE contractures were both inhibited by H, HA and HBH. NE contractures were more sensitive to the effects of H and K ⁺ contractures. These results are consistent with the conclusion that H and hydrazone derivatives produce effects on vascular muscle both by interactions with the fluxes of Ca ⁺⁺ from the extracellular space and effects on release from cell stores. However, other possibilities need to be assessed experimentally.