title: Lack of nitrate tolerance in isosorbid dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter.
abstract: OBJECTIVE
  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 multiply 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.
  
  
  CONCLUSIONS
  This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.
authors.affiliation: Department of General Surgery, School of Medicine, Cumhuriyet University, Sivas, Turkey. akoyuncu@cumhuriyet.edu.tr
authors.forename: Ayhan
authors.initials: A
authors.lastname: Koyuncu
authors.forename: Ihsan
authors.initials: I
authors.lastname: Bagcivan
authors.forename: Bulent
authors.initials: B
authors.lastname: Sarac
authors.forename: Cengiz
authors.initials: C
authors.lastname: Aydin
authors.forename: Sahin
authors.initials: S
authors.lastname: Yildirim
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Sarioglu
mesh_terms: D001003:Anal Canal / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D023421:Models, Animal; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D009566:Nitrates; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D007548:Isosorbide Dinitrate