Koyuncu A, Bagcivan I, Sarac B, Aydin C, Yildirim S, Sarioglu Y. Lack of nitrate tolerance in isosorbide dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter. World J Gastroenterol 2008; 14(29): 4667-4671 [PMID: 18698681 DOI: 10.3748/wjg.14.4667]
Corresponding Author of This Article
Ayhan Koyuncu, MD, Department of General Surgery, School of Medicine, Cumhuriyet University, Sivas 58140, Turkey. akoyuncu@cumhuriyet.edu.tr
Article-Type of This Article
Rapid Communication
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Ayhan Koyuncu, Cengiz Aydin, Department of General Surgery, Faculty of Medicine, Cumhuriyet University, Sivas 58140, Turkey
Ihsan Bagcivan, Bulent Sarac, Sahin Yildirim, Department of Pharmacology, Faculty of Medicine, Cumhuriyet University, Sivas 58140, Turkey
Yusuf Sarioglu, Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara 06500, Turkey
Author contributions: Koyuncu A, Bagcivan I, and Aydin C contributed equally to this work; Koyuncu A, Aydin C, Sarioglu Y designed research; Koyuncu A, Bagcivan I, Sarac B, Yildirim S performed research, Bagcivan I, Yildirim S analyzed data; and Koyuncu A, Bagcivan I and Aydin C wrote the paper.
Correspondence to: Ayhan Koyuncu, MD, Department of General Surgery, School of Medicine, Cumhuriyet University, Sivas 58140, Turkey. akoyuncu@cumhuriyet.edu.tr
Telephone: +90-346-2580492
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Received: March 12, 2008 Revised: April 30, 2008 Accepted: May 7, 2008 Published online: August 7, 2008
Abstract
AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitroprusside (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 (10-7-10-4 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 Emax 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.
