COMPARATIVE EVALUATION OF THE in vitro EFFECTS OF HYDRALAZINE AND HYDRALAZINE ACETONIDE ON ARTERIAL SMOOTH MUSCLE

Dose‐response relationships to K+ were determined in isolated strips of rabit aorta. K⁺ contractures were induced by 30 mM K⁺ in paired strips from individual animals. The effects of hydralazine and hydralazine acetone hydrazone (hydralazine acetonide) on these contractures were studied. Hydralazine and hydralazine acetonide both produced dose‐dependent decreases of K⁺‐induced tone. Threshold concentrations for hydralazine were 11.89 ± 4.5 × 10⁻⁵ M (mean ± s.d.) and for hydralazine actonide 9.7 ± 4.6 × 10⁻⁵ M (0.5 < P < 0.4). The magnitude of the effect of hydralazine acetonide was greater than that of hydralazine at all concentrations above threshold, as reflected in a significant difference (P < 0.05) in the slopes of dose‐response curves to the two treatments. The vasodilator effects of hydralazine and the acetonide were terminated by washout of the bath. The differences in effect were not due to instability of hydralazine under in vitro conditions. It is concluded that hydralazine acetonide has intrinsic activity on vascular smooth muscle which differs significantly from that of the parent compound and that this may contribute to the hypotensive effects which follow administration of the parent compound. 1977 British Pharmacological Society