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European journal of pharmacology

Modulation by NADPH oxidase of the chronic cardiovascular and autonomic interaction between cyclosporine and NSAIDs in female rats.


PMID 28416371

Abstract

Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we investigated: (i) the interaction of CSA with NSAIDs possessing variable COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho-kinase (ROCK) pathway in the interaction. Female rats were pre-instrumented with femoral catheters and treated for 10 days with CSA (25mg/kg/day), diclofenac (nonselective NSAIDs, 1mg/kg/day), celecoxib (COX2 inhibitor, 10mg/kg/day), or their combinations. CSA-mediated hypertension was maintained upon co-administration of either NSAID whereas the concomitant reductions in time- and frequency-domain indices of heart rate variability (HRV) were accentuated in presence of diclofenac but not celecoxib. The isovolumic relaxation time (Τau), a measure of diastolic function, was reduced by all regimens whereas LV contractility (dP/dt

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