Nitric oxide mediated the effects of nebivolol in cardiorenal syndrome

Document Type: Original Article

Authors

1 University of Health Sciences, Faculty of Pharmacy, Department of Pharmacology, Istanbul-Turkey

2 Istanbul University, Istanbul Medical Faculty, Department of Pathology, Istanbul-Turkey

Abstract

Objective(s): Despite several proposed mechanisms for the pathophysiology of cardiorenal syndrome (CRS), the exact mechanism remains unclear. Nitrosative stress has been argued as a key mechanism recently. Nebivolol is a beta-blocker with nitric oxide (NO)-releasing effect. In the present study, NO-mediated effects of two different treatment regimes of nebivolol in CRS were studied.
Materials and Methods: Rats were divided into: sham-operated (sham-control), myocardial infarction (MI)-induced, (MI-control) early nebivolol-treated (MI-neb1) and late nebivolol-treated (Mı-neb2) groups. The effects of nebivolol were assessed both in the early and late period of MI by histologic, hemodynamic and biologic studies.
Results: Developed MI model was in line with the heart failure with preserved ejection fraction. Focal and total tubular damage findings were observed in MI-control group both in early and late period of MI. In parallel, subclinical functional damage was transformed into chronic renal dysfunction in this group.  Increased inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) together with decreased neuronal NOS (nNOS) levels were in parallel with the increased inflammation and nitrosative stress biomarkers. Nebivolol effectively prevented both subclinical and clinical nephropathy. There was no statistical difference between the nebivolol treatment regimes.
Conclusion: The beneficial effects of nebivolol were closely related to the reduction of nitrosative damages as well as hemodynamic alterations. The NO-mediated effects were: prevention of nitrosative damage by decreasing iNOS, preservation of nNOS in order to maintain glomerular filtration rate (GFR), and restoration of eNOS in the late period of MI. On contrary to our previous work, early nebivolol administration had a similar effect with delayed administration of nebivolol on CRS.

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