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Beta3-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase activation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Aragón, Juan P. Condit, Marah E. Bhushan, Shashi Predmore, Benjamin L. Patel, Sandeep S. Grinsfelder, D. Bennett Gundewar, Susheel Jha, Saurabh Calvert, John W. Barouch, Lili A. Lavu, Madhav Wright, Harold M. Lefer, David J. |
| Copyright Year | 2011 |
| Abstract | OBJECTIVES This paper examined whether nebivolol protects the heart via nitric oxide (NO) synthase and NO-dependent signaling in an in vivo model of acute myocardial infarction. BACKGROUND Beta(3)-adrenergic receptor (AR) activation promotes endothelial nitric oxide synthase (eNOS) activity and NO bioavailability. We hypothesized that specific beta(3)-AR agonists would attenuate myocardial ischemia-reperfusion (MI/R) injury via eNOS activation and increased NO bioavailability. METHODS Mice were subjected to 45 min of myocardial ischemia in vivo followed by 24 h of reperfusion (R). Nebivolol (500 ng/kg), CL 316243 (1 μg/kg), BRL-37344 (1 μg/kg), or vehicle (VEH) was administered at the time of R. Myocardial area-at-risk (AAR) and infarct size (INF)/AAR was measured at 24 h of R. Cardiac tissue and plasma were collected to evaluate eNOS phosphorylation, neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase expression, and nitrite and nitrosothiol levels. RESULTS Nebivolol (500 ng/kg) reduced INF/AAR by 37% (p < 0.001 vs. VEH) and serum troponin-I levels from 41 ± 4 ng/ml to 25 ± 4 ng/ml (p < 0.05 vs. VEH). CL 316243 and BRL-37344 reduced INF by 39% and 42%, respectively (p < 0.001 vs. VEH). Nebivolol and CL 316243 increased eNOS phosphorylation at Ser-1177 (p < 0.05 vs. VEH) and increased nitrite and total nitrosylated protein levels. Nebivolol and CL 316243 significantly increased myocardial nNOS expression. Nebivolol failed to reduce INF after MI/R in beta(3)-AR (-/-), eNOS(-/-), and in nNOS(-/-) mice. CONCLUSIONS Our results indicate that beta(3)-AR agonists protect against MI/R injury. Furthermore, the cardioprotective effects of beta(3)-AR agonists are mediated by rapid eNOS and nNOS activation and increased NO bioavailability. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.jacc.2011.09.033 |
| PubMed reference number | 22152956 |
| Journal | Medline |
| Volume Number | 58 |
| Issue Number | 25 |
| Alternate Webpage(s) | http://www.onlinejacc.org/content/accj/58/25/2683.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1016/j.jacc.2011.09.033 |
| Journal | Journal of the American College of Cardiology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
