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-, nit ro-, azoxy- and N,N'-dioxide-derivatives) were studied in the rat aort ic strip suspended in the bath medium. In the CaCl2-free bath medium c ontaining 40 mM KCl, CaCl2 (2.5 mM) induced contraction, which was rel axed by nifedipine (-log [EC(50)] = 8.66 M) and all the four photodegr adation products (-log[EC(50)] = 4.15 - 4.82 M). The EC(50) values for all these substances were not affected by denuding the vessel of endo thelium. 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)-1 0(-6) M) and its four photodegradation products (3 x 10(-6)-10(-4) M). Norepinephrine (10(-7) M) induced contraction, which was relaxed by t he nitroso-derivative (10(-4) M) noncompetitively (pIC(50) = 4.37) but not by three other photodegradation products. Both methylene blue and hemoglobin had no effect on the relaxation produced by the nitroso-de rivative. Phorbol 12-myristate 13-acetate induced contraction, which w as inhibited completely by the nitroso-derivative (10(-4) M) but Only by 42% by nifedipine (10(-4) M). Prostaglandin F-2 alpha (3 x 10(-6) M ), endothelin-1 (10(-9) M) and 5-hydroxytryplamine (10(-6) M) also ind uced contraction, which was relaxed effectively by the nitroso-derivat ive (10(-4) M) but not by any of the three other photodegradation prod ucts. We conclude that all the four photodegradation products of nifed ipine have a weak voltage-dependent Ca++ channel blocking action and t hat the nitroso-derivative, unlike three other photodegradation produc ts, relaxes the aortic strip contracted by norepinephrine, prostagland in F-2 alpha, endothelin-1 or 5-hydroxytryptamine probably by inhibiti ng the protein kinase C and not by releasing nitric oxide.