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Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats
| Content Provider | Scilit |
|---|---|
| Author | Varagic, Jasmina Ahmad, Sarfaraz Voncannon, Jessica L. Moniwa, Norihito Simington, Stephen W. Brosnihan, Bridget K. Gallagher, Patricia E. Habibi, Javad Sowers, James R. Ferrario, Carlos M. |
| Copyright Year | 2012 |
| Description | Journal: Journal of Hypertension Objectives: Increased sympathetic outflow, renin–angiotensin system (RAS) activity, and oxidative stress are critical mechanisms underlying the adverse cardiovascular effects of dietary salt excess. Nebivolol is a third-generation, highly selective β1-receptor blocker with RAS-reducing effects and additional antioxidant properties. This study evaluated the hypothesis that nebivolol reduces salt-induced cardiac remodeling and dysfunction in spontaneous hypertensive rats (SHRs) by suppressing cardiac RAS and oxidative stress. Methods: Male SHRs (8 weeks of age) were given an 8% high salt diet (HSD; n = 22), whereas their age-matched controls (n = 10) received standard chow. In a subgroup of HSD rats (n = 11), nebivolol was given at a dose of 10 mg/kg per day by gastric gavage. Results: After 5 weeks, HSD exacerbated hypertension as well as increased left-ventricular weight and collagen deposition while impairing left-ventricular relaxation. Salt-induced cardiac remodeling and dysfunction were associated with increased plasma renin concentration (PRC), cardiac angiotensin II immunostaining, and angiotensin-converting enzyme (ACE)/ACE2 mRNA and activity ratio. HSD also increased cardiac 3-nitrotyrosine staining indicating enhanced oxidative stress. Nebivolol treatment did not alter the salt-induced increase in arterial pressure, left-ventricular weight, and cardiac dysfunction but reduced PRC, cardiac angiotensin II immunostaining, ACE/ACE2 ratio, oxidative stress, and fibrosis. Conclusions: Our data suggest that nebivolol, in a blood pressure-independent manner, ameliorated cardiac oxidative stress and associated fibrosis in salt-loaded SHRs. The beneficial effects of nebivolol may be attributed, at least in part, to the decreased ACE/ACE2 ratio and consequent reduction of cardiac angiotensin II levels. |
| Related Links | http://europepmc.org/articles/pmc3567851?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567851/pdf |
| Ending Page | 1774 |
| Page Count | 9 |
| Starting Page | 1766 |
| ISSN | 02636352 |
| e-ISSN | 14735598 |
| DOI | 10.1097/hjh.0b013e328356766f |
| Journal | Journal of Hypertension |
| Issue Number | 9 |
| Volume Number | 30 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2012-09-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Hypertension Β1-adrenergic Receptors Angiotensin Ii Blood Pressure Cardiac Fibrosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Internal Medicine Cardiology and Cardiovascular Medicine |
