Mechanism of hydralazine-induced relaxation of arterial smooth muscle.
The effect of hydralazine on contractile responses by various agents has been studied in isolated rat tail artery strips. Hydralazine caused dose-dependent relaxation of contractions produced by 10(-7) mol.litre-1 noradrenaline (N); 10(-7) mol.litre-1 5-HT or 100 mmol.litre-1 KCl, suggesting that the relaxation response is non-specific. CaCl2 dose-response (in the presence of 10(-5) mol.litre-1 N; 10(-5) mol.litre-1 5-HT or 100 mmol.litre-1 KC1) was significantly inhibited by 5 X 10(-4) mol.litre-1 hydralazine in the order: KCl greater than 5-HT greater than N. Hydralazine also inhibited BaCl2 dose-response curve (in K+-depolarised strips); maximal contraction to BaCl2 was depressed by 87%. In other experiments, hydralazine significantly depressed (by 20%) the phasic contractile response to N due to mobilisation of calcium from a membrane-bound pool. D 600, a calcium entry blocker, also caused dose-dependent relaxation of contractile responses to all three agents studied; and inhibited CaCl2 and BaCl2 dose-response curves in K+-depolarised media, as well as depressed the phasic contractile response to N in Ca-free media by 17%. These results suggest that in the rat tail artery, hydralazine interferes with Ca2+ influx, as well as release from a membrane-bound pool.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002118:Calcium / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology
D017609:Barium Compounds; D002712:Chlorides; C024986:barium chloride; D001464:Barium; D006830:Hydralazine; D012701:Serotonin; D005711:Gallopamil; D011189:Potassium Chloride; D002122:Calcium Chloride; D002118:Calcium; D009638:Norepinephrine