Divergent Effects for Celecoxib and Diclofenac on Hemodynamic and Left Ventricular Actions of Cyclosporine in Female Rats

Abstract

The combined use of cyclosporine (CSA), a potent immunosuppressant, and nonsteroidal antiinflammatory drugs (NSAIDs) in arthritis is a common clinical practice. In this study, we evaluated whether diclofenac (nonselective COX‐1/COX‐2 inhibitor) and celecoxib (selective COX‐2 inhibitor) interact variably with CSA hemodynamics in conscious female rats. Changes evoked by acutely administered CSA in blood pressure (BP), heart rate (HR), HR variability (HRV), and myocardial contractility were assessed in the absence and presence of diclofenac or celecoxib. Compared with vehicle values, CSA (10 mg/kg i.v.) caused immediate and sustained increases in BP and decreases in the pulse pressure index and HR. CSA also increased the time and frequency domain indices of HRV and shifted the cardiac sympathovagal balance towards parasympathetic dominance. The pressor effect of CSA was intensified and abolished in rats pretreated i.v. with diclofenac (10 mg/kg) and celecoxib (10 mg/kg), respectively. The autonomic and PPI effects of CSA were blunted in the presence of celecoxib in contrast to no effect for diclofenac. We also report that celecoxib, but not diclofenac, eliminated the elevated LV contractility (dP/dtmax) and isovolumic relaxation constant (Τau, τ), which reflects the cardiac diastolic function, that accompanied the CSA‐evoked pressure load. The data highlight the preferential capacity of celecoxib to mitigate the pressor effect of CSA and consequent alterations in cardiac performance and autonomic balance in female rats.Supported by the ALEX‐REP Grant Fund, Alexandria University, Egypt (Grant HLTH‐13‐01).