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Interactions between inducible nitric oxide synthase and cyclooxygenase‐2 in response to ischaemia‐reperfusion of rabbit bladder
Author(s) -
Masuda Hitoshi,
Kawano Keizo,
Matsuoka Yoh,
Yokoyama Minato,
Koga Fumitaka,
Saito Kazutaka,
Kihara Kazunori,
Azuma Hiroshi
Publication year - 2010
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2009.09143.x
Subject(s) - nitric oxide synthase , cyclooxygenase , rabbit (cipher) , nitric oxide , atp synthase , ischemia , pharmacology , chemistry , medicine , biochemistry , enzyme , computer science , computer security
OBJECTIVE To investigate the interactions between inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in response to ischaemia‐reperfusion (I/R) of rabbit bladder. MATERIALS AND METHODS Rabbit bladders were exposed to 2 h of ischaemia by bilaterally clamping the major arteries entering the bladder and then a subsequent 36 h of reperfusion (I/R) with or without intraperitoneal administration of a selective iNOS inhibitor n ‐(3‐(amynomethyl)benzyl)acetamidine (1400W) or a selective COX‐2 inhibitor NS‐398 given 1 h before killing. The bladder tissues were processed for isometric tension experiments, enzymatic NOS activitiy, tissue contents of nitrite/nitrate (NO X ), cyclic guanosine monophosphate (cGMP) and COX activity determined by prostaglandin E 2 (PGE 2 ) production. RESULTS iNOS and constitutive NOS (cNOS) activities, NO X and PGE 2 contents in the bladder tissues at 36 h after reperfusion were significantly higher than those in the sham group with no significant increase in cGMP. Treatment with 1400W abrogated the increases in iNOS activity and NO X as well as PGE 2 without changing cNOS activity. In the tension experiments, a NOS substrate, l ‐arginine, induced detrusor contraction only in the I/R group, which was inhibited by 1400W or NS‐398 but not by a selective soluble guanylate cyclase inhibitor 1H‐[1,2,4] oxadiazole[4,3‐a]quinoxalin‐1‐one (ODQ). 8‐Br‐cGMP induced detrusor relaxation in the sham and I/R groups. Also, l ‐arginine increased NO X and PGE 2 in the bladder tissues only in the I/R group, which were inhibited by pretreatment with 1400W. While, l ‐arginine increased cGMP contents in the I/R group and this increase was suppressed by ODQ but not by 1400W. CONCLUSION These results show that NO derived from an up‐regulation of iNOS after I/R increases COX‐2‐derived PG via a cGMP‐independent mechanism. NO‐mediated activation of COX‐2 may be an important mechanism for the modulation of bladder function after I/R injury.