Effects of photodegradation products of nifedipine: the nitroso-derivative relaxes contractions of the rat aortic strip induced by norepinephrine and other agonists.
Effects of four photodegradation products of nifedipine (nitroso-, nitro-, azoxy- and N,N'-dioxide-derivatives) were studied in the rat aortic strip suspended in the bath medium. In the CaCl2-free bath medium containing 40 mM KCl, CaCl2 (2.5 mM) induced contraction, which was relaxed by nifedipine (-log [EC50] = 8.66 M) and all the four photodegradation products (-log[EC50] = 4.15-4.82 M). The EC50 values for all these substances were not affected by denuding the vessel of endothelium. In the bath medium containing KCl (15 mM), Bay K-8644 (2 x 10(-6) M) induced contraction, which was relaxed by nifedipine (10(-9)-10(-6) M) and its four photodegradation products (3 x 10(-6)-10(-4) M). Norepinephrine (10(-7) M) induced contraction, which was relaxed by the nitroso-derivative (10(-4) M) noncompetitively (pIC50 = 4.37) but not by three other photodegradation products. Both methylene blue and hemoglobin had no effect on the relaxation produced by the nitroso-derivative. Phorbol 12-myristate 13-acetate induced contraction, which was inhibited completely by the nitroso-derivative (10(-4) M) but only by 42% by nifedipine (10(-4) M). Prostaglandin F2 alpha (3 x 10(-6) M), endothelin-1 (10(-9) M) and 5-hydroxytryptamine (10(-6) M) also induced contraction, which was relaxed effectively by the nitroso-derivative (10(-4) M) but not by any of the three other photodegradation products.(ABSTRACT TRUNCATED AT 250 WORDS)
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002122:Calcium Chloride / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010777:Photochemistry; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000470:Alkaloids; D016232:Endothelins; D006454:Hemoglobins; D009603:Nitroso Compounds; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015237:Dinoprost; D011493:Protein Kinase C; D019311:Staurosporine; D009543:Nifedipine; D002122:Calcium Chloride; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D008751:Methylene Blue; D009638:Norepinephrine