Lack of nitrate tolerance in isosorbid dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter
Abstract
AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitropruside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS: Relaxation responses of ISDN, and electrical field stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. RESULTS: ISDN (10(-7)-10(-7) mol/L) and SNP (10(-8)-10(-4) mol/L caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 x 10(-4) mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and E(max) obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. CONCLUSION: This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance. (c) 2008 The WIG Press. All rights reserved.
Source
WORLD JOURNAL OF GASTROENTEROLOGYVolume
14Issue
29Collections
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