Nebivolol Improves Diastolic Dysfunction and Myocardial Remodeling Through Reductions in Oxidative Stress in the Zucker Obese Rat
Open accessAbstract
Insulin resistance is associated with obesity and may be accompanied by left ventricular diastolic dysfunction and myocardial remodeling. Decreased insulin metabolic signaling and increased oxidative stress may promote these maladaptive changes. In this context, the β-blocker nebivolol has been reported to improve insulin sensitivity, increase endothelial NO synthase activity, and reduce NADPH oxidase–induced superoxide generation. We hypothesized that nebivolol would attenuate diastolic dysfunction and myocardial remodeling by blunting myocardial oxidant stress and promoting insulin metabolic signaling in a rodent model of obesity, insulin resistance, and hypertension. Six-week–old male Zucker obese and age-matched Zucker lean rats were treated with nebivolol (10 mg · kg − · day −1 ) for 21 days, and myocardial function was assessed by cine MRI. Compared with untreated Zucker lean rats, untreated Zucker obese rats exhibited prolonged diastolic relaxation time (27.7±2.5 versus 40.9±2.0 ms; P <0.05) and reduced initial diastolic filling rate (6.2±0.5 versus 2.8±0.6 μL/ms; P <0.05) in conjunction with increased homeostatic model assessment of insulin resistance (7±2 versus 95±21; P <0.05), interstitial and pericapillary fibrosis, abnormal cardiomyocyte histoarchitecture, 3-nitrotyrosine, and NADPH oxidase–dependent superoxide. Nebivolol improved diastolic relaxation (32.8±0.7 ms; P <0.05 versus untreated Zucker obese), reduced fibrosis, and remodeling in Zucker obese rats, in concert with reductions in nitrotyrosine, NADPH oxidase–dependent superoxide, and improvements in the insulin metabolic signaling, endothelial NO synthase activation, and weight gain (381±7 versus 338±14 g; P <0.05). Results support the hypothesis that nebivolol reduces myocardial structural maladaptive changes and improves diastolic relaxation in concert with improvements in insulin sensitivity and endothelial NO synthase activation, concomitantly with reductions in oxidative stress.
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Treatment with β-blockers leads to metabolic complications including weight gain.
“Given that excessive sympathetic activity is common in obesity, β-blockers appear as an obvious pharmacologic therapy to treat the hypertension associated with this condition, but treatment with β-blockers leads to metabolic complications including weight gain (16–18).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [17]
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References 92 · Cited by 116
- Authors
- Zhou, X., Ma, L., Habibi, J., Whaley-Connell, A., Hayden, M. R., Tilmon, R. D., Brown, A. N., Kim, J.-A., DeMarco, V. G., & Sowers, J. R.
- Affiliations
- Shandong University (CN)
- From the Provincial Hospital affiliated to Shandong University (X.Z.), Jinan, China; Departments of Internal Medicine (X.Z., J.H., A.W.-C., M.R.H., R.D.T., J.K., V.G.D., J.R.S.), Radiology (L.M., A.N.B.), and Medical Pharmacology and Physiology (V.G.D.), University of Missouri School of Medicine, Columbia, Mo; Harry S. Truman Veterans Affairs’ Medical Center (X.Z., L.M., J.H., A.W.-C., A.N.B., J.K., J.R.S.), Columbia, Mo.
- Venue
- Hypertension
- Published
- 2010-04
- Volume
- 55
- Issue
- 4
- Pages
- 880-888
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC2841702
- OpenAlex
- W2138377901
- Cited by
- 116
- References
- 92
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 15 · 2012: 17
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Missouri
- National Institutes of Health (HL73101, R01 HL73101-01A1)
- National Heart, Lung, and Blood Institute (R01 HL73101‑01A1, R01HL073101)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nebivolol, diastolic dysfunction, cardiac remodeling, oxidative stress, insulin resistance, obesity, Zucker fatty rats, beta-blockers, endothelial nitric oxide synthase, NADPH oxidase, superoxide, nitrotyrosine, myocardial fibrosis, diastolic relaxation
- MeSH terms
- Nebivolol, Analysis of Variance, Animals, Benzopyrans, Blood Glucose, Ethanolamines, Fluorescent Antibody Technique, Hypertension, Insulin, Insulin Resistance, Magnetic Resonance Imaging, Male, Mitochondria, Obesity, Rats, Zucker, Blotting, Western, Signal Transduction, Oxidative Stress, Ventricular Dysfunction, Left, Ventricular Remodeling, Metabolic Syndrome, Proto-Oncogene Proteins c-akt, Rats, Nitric Oxide Synthase Type III, Insulin Receptor Substrate Proteins
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