Zhao, Xin and Park, Jiyeon and Ho, David and Gao, Shumin and Yan, Lin and Ge, Hui and Iismaa, Siiri E and Lin, Lin and Tian, Bin and Vatner, Dorothy E and Graham, Robert M and Vatner, Stephen F (2012) Cardiomyocyte overexpression of the α1A-adrenergic receptor in the rat phenocopies second but not first window preconditioning. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 302 (8). pp. H1614-24. ISSN 1522-1539 (PMC OA)
Full text not available from this repository.Abstract
We examined α(1A)-adrenergic receptor (AR) mediation of preconditioning in a novel α(1A)-AR cardiac transgenic (TG) rat model (α(1A)-TG). Compared with nontransgenic littermates (NTLs), in conscious α(1A)-TG rats, heart rate was reduced, contractility [left ventricle (LV) +dP/dt, ejection fraction, end-systolic elastance] was significantly enhanced, and triple product (LV systolic wall stress × LV +dP/dt × heart rate) was unchanged. However, infarct size (IS)/area at risk (AAR) in response to ischemia-reperfusion (30 min coronary occlusion/3 h reperfusion) was reduced to 35 ± 4.6% in α(1A)-TGs vs. 52 ± 2.2% in NTLs (P < 0.05). Second window preconditioning reduced IS/AAR in NTLs to 29 ± 2.7% but did not afford further protection in α(1A)-TGs. In contrast, with first window preconditioning, IS/AAR was reduced to similar levels in both α(1A)-TGs (12 ± 1.4%) and NTLs (10 ± 1.1%). In untreated α(1A)-TGs, cardioprotection was associated with enhanced myocardial phosphorylated (p)-mitogen/extracellular signal-regulated kinase (MEK), p-extracellular signal-regulated kinase (ERK), and inducible nitric oxide synthase (iNOS) at the protein level, along with a 1.3-fold increase in total nitric oxide synthase activity like in second window preconditioning. Affymetrix microarrays revealed that few genes (4.6% of 3,172 upregulated; 8.8% of 3,498 downregulated) showed directionally similar changes in α(1A)-TGs vs. NTLs subjected to second window preconditioning. Thus, second, but not first, window cardioprotection is evident in α(1A)-TGs in the absence of ischemic preconditioning and is mediated by iNOS activation associated with MEK/ERK phosphorylation. Transcriptionally, however, second window preconditioning is considerably more complex than α(1A)-TG preconditioning, with the alteration of thousands of additional genes affording no further protection than that already available in α(1A)-TG rats.
(National Institutes of Health NIH Grants 5P01HL-069020, 5R01HL-033107, 5P01AG-027211, 1R01HL-102472, 5T32HL-069752, 5R01HL-095888, 5R01HL-091781, 5R01HL-093415 and 5R01HL-093481; NHMRC Grants 526622 and 573732, Heart Foundation of Australia grant G0954342).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 Jan 2016 00:03 |
| Last Modified: | 09 Mar 2018 05:26 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/95 |
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