Studies on endothelium-dependent vasorelaxation by hydralazine in porcine coronary artery

Hydralazine relaxed porcine coronary artery strips in a concentration-dependent manner by distinct endothelium-dependent and endothelium-independent actions. With lower doses (≤ 10^-6 M), the hydralazine-induced relaxation appears to be completely endothelium-dependent and we designed the present study to elucidate the mechanisms of this endothelium-dependent relaxation. Hydralazine (10^-6 M)-induced endothelium-dependent relaxation was not affected by the presence of 10^-5 M indomethacin, 10^-3 M L-N(G)-nitro-arginine (L-NOARG) or 10^-5 M haemoglobin, and was accompanied by accumulation of cGMP but not of cAMP in artery strips. There was a close time-dependent parallel relationship between endothelium-dependent relaxation and accumulation of cGMP induced by hydralazine (10^-6 M). The endothelium-dependent relaxation and accumulation of cGMP induced by hydralazine showed much slower kinetics than those induced by ionomycin (10^-7 M). Pretreatment of the strips with actinomycin D (10 μg/ml) significantly inhibited not the endothelium-dependent relaxation and accumulation of cGMP induced by ionomycin (10^-7 M) but those induced by hydralazine (10^-6 M). These results suggest that hydralazine induces endothelium-dependent vasorelaxation via the slow accumulation of cGMP in the strips. This does not occur through the release of nitric oxide or prostaglandin I₂ but through immediate transcription and probably expression of a molecule in the endothelium.