Alteration in myocardial prostaglandin D synthase expression in pressure overload-induced left ventricular remodeling in rats.
We hypothesized that acute pharmacological blockade of cyclooxygenase-2 (COX-2) using nimesulide (Nime) would prevent maladaptive changes in left ventricular (LV) structure and function secondary to abdominal aortic coarctation-induced pressure overload (PO). In vivo LV chamber dimension and function were assessed by pressure/volume admittance catheter at 14 days' postsurgery in three groups (n ≥ 6/group): sham-operated (Sham); untreated PO; and selective COX-2 inhibitor nimesulide-treated PO (PO + Nime; 25 mg/kg/d). Treatment was initiated 24 h prior to surgical induction of PO. Relative to Sham, there was a marked increase in LV mass index in the PO groups (2.2 ± 0.01 mg/g versus 2.9 ± 0.10 mg/g Sham versus PO, PO+Nime: 2.5 ± 0.03 mg/g). End diastolic volume, an indicator of chamber size, was significantly decreased in the PO animals compared with Sham (202 ± 17μL versus 143 ± 16 μL Sham versus PO, PO + Nime: 226 ± 9 μL). Collagen levels in PO rats assessed by hydroxyproline analysis were significantly elevated relative to Sham values. Nimesulide treatment attenuated: (1) the increase in LV mass index; (2) the reduction in end diastolic volume; and (3) the PO-induced increase in myocardial collagen. In summary, acute COX-2 inhibition with nimesulide attenuated the maladaptive changes in the LV after PO. Acknowledging the clinical failure of chronic COX-2 inhibitor use, we propose that acute treatment with COX-2 inhibition during the initial stages of cardiac remodeling can be beneficial in maintaining the normal cardiac structure and function during PO.
Department of Pharmacology, University of Mississippi, University, MS 38677, USA.
Krishna T
KT
Nagalla
Monica
M
Gole
Mario A
MA
Claudino
Jason D
JD
Gardner
David B
DB
Murray
D000818:Animals; D001017:Aortic Coarctation / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000187:drug effects*
D052246:Cyclooxygenase 2 Inhibitors; D054834:Lipocalins; D013449:Sulfonamides; D003094:Collagen; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; C012655:nimesulide