Heme oxygenase byproducts variably influences myocardial and autonomic dysfunctions induced by the cyclosporine/diclofenac regimen in female rats.

Heme oxygenase byproducts variably influences myocardial and autonomic dysfunctions induced by the cyclosporine/diclofenac regimen in female rats. Biomed Pharmacother. 2018 May;101:889-897 Authors: Ibrahim KS, El-Yazbi AF, El-Gowelli HM, El-Mas MM Abstract We recently reported that exposure to cyclosporine (CSA) plus diclofenac causes hypertension and impairs left ventricular (LV) and cardiac autonomic functions in female rats. Here, we tested the hypothesis that these effects could be mitigated by facilitated heme oxygenase (HO) signaling. Experiments were performed in female rats to assess the effects of 10-day treatment with CSA (25 mg/kg/day)/diclofenac (1 mg/kg/day) regimen on cardiovascular functions in absence and presence of maneuvers that upregulate HO or its enzymatic products. The CSA/diclofenac-induced hypertension and impairment in cardiac sympathovagal balance (i.e. reduced low-frequency/high-frequency spectral ratio) were blunted upon concurrent treatment with hemin (HO-1 inducer), tricarbonyldichlororuthenium (II) dimer (CORM-2, carbon monoxide-releasing molecule), or bilirubin. While none of the latter treatments affected the CSA/diclofenac-evoked decrease in isovolumic relaxation constant (Tau, a measure of diastolic function), the increased LV contractility (dP/dtmax) and attenuated reflex bradycardia in CSA/diclofenac-treated rats was abolished by bilirubin only. Paradoxically, the CSA/diclofenac-evoked attenu...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research