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Aging Exaggerates Angiotensin II‐Induced Reduction of Coronary Reactive Hyperemia in Isolated Mouse Heart
Author(s) -
Hanif Ahmad,
Nayeem Mohammed A
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb770
Subject(s) - medicine , reactive hyperemia , angiotensin ii , endocrinology , cardiology , endothelial dysfunction , heart rate , coronary circulation , circulatory system , endothelium , ischemia , coronary flow reserve , heart failure , blood pressure , blood flow
Coronary reactive hyperemia (CRH) is an indirect measure of coronary reserve, and its impairment is associated with cardiovascular disease. Aging is accompanied with blunting of many physiological functions. Moreover, aging is associated with increased angiotensin II (Ang II) levels. Ang II has powerful effects on many organs including coronary endothelium. In the vascular system, Ang II acts as a potent vasoconstrictor and produces endothelial dysfunction and smooth muscle proliferation. However, it's not known what effect aging could have on CRH. We hypothesized that aging causes older mice (50 weeks) to have reduced CRH compared to younger mice (16 weeks) and Ang II modulates CRH more negatively in aging mice compared to younger ones. Coronary flow (CF) in isolated mouse heart from young and aging C57BL6J mice (WT) was measured using Langendorff system. Perfused isolated heart was exposed to 15 second ischemia and CRH was assessed. Following ischemia, flow repayment volume [RV, the area under the curve normalized to heart weight (ml/g)] was significantly decreased in aging vs. young mice (5.5 ± 0.3 vs. 7.4 ± 0.8, p<0.05, Fig. 1). Repayment to debt ratio was also decreased in aging vs. young mice (2.1 ± 0.3 to 1.6 ± 0.1, p<0.05, Fig. 2). Baseline coronary flow, heart Rate and left ventricular pressure (LVP) were not different between young and aging mice. When Ang II (1nM) was perfused, it significantly decreased RV in young (7.4 ± 0.8 to 5.5 ± 0.3, p<0.05) as well as in aging mice (5.5 ± 0.3 to 3.2 ± 0.4, p<0.05, Fig. 1). Ang II also decreased repayment duration (min) in young (2.5 ± 0.2 to 1.2 ± 0.3, p<0.05) as well as aging mice (2.7 ± 0.4 to 1.3 ± 0.3, p<0.05, Fig. 3). Heart rate was not affected by Ang II in either group. Our results demonstrate that aging mice have significant reduction in CRH compared to young mice (p<0.05) independent of Ang II effect, and after Ang II perfusion, a drastic reduction in CRH in both young and aging mice was observed. These data suggest that both aging and Ang II have negative effects on myocardial recovery from ischemic insult. Support or Funding Information Supported by HL‐114559 to MAN. 123