Title | Opposite Modulatory Effects of Selective and Non-Selective Cyclooxygenase Inhibition on Cardiovascular and Autonomic Consequences of Cyclosporine in Female Rats. | ||
Author | Ibrahim, Karim S; El-Yazbi, Ahmed F; El-Gowelli, Hanan M; El-Mas, Mahmoud M | ||
Journal | Basic Clin Pharmacol Toxicol | Publication Year/Month | 2017-Jun |
PMID | 28054752 | PMCID | -N/A- |
Affiliation | 1.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. |
Non-steroidal anti-inflammatory drugs (NSAIDs) and the immunosuppressant drug cyclosporine (CSA) are concurrently administered in arthritis. Here, we investigated whether diclofenac (non-selective inhibitor of cyclooxygenase-1 and 2, COX-1/COX-2), celecoxib (selective COX-2 inhibitor) or SC560 (selective COX-1 inhibitor) interact variably with haemodynamic effects of CSA in conscious female rats. Changes caused by CSA (10 mg/kg i.v.) in blood pressure (BP), heart rate (HR), HR variability (HRV) and myocardial contractility were assessed in the absence and presence of individual NSAIDs (10 mg/kg each). Compared with vehicle values, CSA caused immediate and sustained (i) increases in BP and decreases in pulse pressure index (PPI) and HR, (ii) elevations in left ventricular (LV) contractility (dP/dt(max) ) and isovolumic relaxation constant (Tauau) and (iii) increases in the time- and frequency-domain indices of HRV and shifted the cardiac sympathovagal balance towards parasympathetic dominance. CSA hypertension was abolished in rats pre-treated with celecoxib and intensified in the presence of diclofenac or SC560. Alternatively, the CSA-evoked decreases in PPI, increases in HRV indices and cardiac parasympathetic dominance were blunted by celecoxib in contrast to no effect for diclofenac or SC560. Similarly, celecoxib, but not other NSAIDs, eliminated the elevated LV contractility (dP/dt(max) ) and isovolumic relaxation constant (Tauau, tau), which reflect cardiac systolic and diastolic function, respectively, that accompanied the CSA-induced pressure load. The data underscore the preferential capacity of selective COX-2 inhibition by celecoxib to mitigate CSA hypertension and consequent alterations in cardiac performance and autonomic balance. By contrast, CSA effects are preserved or even exacerbated after COX-1 inhibition.