TY - JOUR T1 - Vasorelaxing effect of S-nitrosocaptopril on dog coronary arteries: no cross-tolerance with nitroglycerin. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1247 LP - 1253 VL - 275 IS - 3 AU - T Matsumoto AU - M Takahashi AU - I Nakae AU - M Kinoshita Y1 - 1995/12/01 UR - http://jpet.aspetjournals.org/content/275/3/1247.abstract N2 - S-Nitrosocaptopril (S-NO-Cap) produced dose-dependent relaxation in isolated dog coronary arteries. This relaxation consisted of two parts: an initial phasic relaxation and a subsequent sustained relaxation. Relaxation was potentiated by superoxide dismutase but was suppressed by pyrogallol, methylene blue or oxyhemoglobin. The relaxant responses of coronary artery to vasoactive agents were reexamined after the development of nitrate tolerance induced by a 1-hr treatment with 4.4 x 10(-4) M nitroglycerin (NTG). NTG tolerance was verified by a 40-fold increase in the EC50 values. The relaxant response to nitroprusside was only marginally suppressed in NTG-tolerant arteries. NTG-tolerant arteries were not tolerant to nitric oxide (NO) or 8-bromo-cyclic guanosine monophosphate (cGMP) and did not show a significant change in the concentration-response curves. Similarly, the concentration-response curves for S-NO-Cap in NTG-tolerant coronary arteries were not significantly different from those in nontolerant coronary arteries. Captopril (5 x 10(-4) M) did not enhance the vasodilative effect of NTG or reverse NTG tolerance. The NTG-induced increase in cGMP was abolished after NTG tolerance was established. On the other hand, the S-NO-Cap-induced increase in cGMP was unaffected by NTG tolerance. In conclusion, these findings indicate that (1) S-NO-Cap is an NO-like substance, (2) an impaired formation of NO or S-nitrosothiol is responsible for the formation of NTG tolerance and (3) S-NO-Cap, which does not show cross-tolerance with NTG, may serve as a therapeutic alternative to current nitrovasodilators. ER -