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 (< or = 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-NG-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 micrograms/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.
Wei
S
S
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Kasuya
Y
Y
Yanagisawa
M
M
Kimura
S
S
Masaki
T
T
Goto
K
K
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D006454:Hemoglobins; D011500:Protein Synthesis Inhibitors; D014665:Vasodilator Agents; D003609:Dactinomycin; D019335:Nitroarginine; D006830:Hydralazine; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP; D007213:Indomethacin