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Angiotensin II Negatively Modulates Coronary Reactive Hyperemia and Over‐expression of Soluble Epoxide Hydrolase Further Aggravates its Effect
Author(s) -
Hanif Ahmad,
Zeldin Darryl C,
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.1198.4
Subject(s) - epoxide hydrolase 2 , angiotensin ii , medicine , chemistry , endocrinology , reactive hyperemia , ischemia , renin–angiotensin system , endothelial dysfunction , enzyme , receptor , vasodilation , blood pressure , biochemistry
Coronary reactive hyperemia (CRH) is impaired in cardiovascular disease. Angiotensin II (Ang II) has powerful short‐ and long‐term 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 is not known if Ang II affects CRH in C57BL/6J mice. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. Soluble epoxide hydrolase (sEH) is the main enzyme responsible for EETs breakdown. In Tie2‐sEH Tr mice, the human endothelial sEH is over‐expressed. This over‐expression results in decreased level of EETs in Tie2‐sEH Tr vs. WT mice. Our previous data showed that CRH was decreased in Tie2‐sEH Tr vs. WT. We hypothesized that Ang II negatively modulates CRH and that over‐expression of sEH further aggravates its effect. Coronary flow (CF) in isolated Tie2‐sEH Tr and WT mouse heart 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 reduced by 40% in WT treated with Ang II (1nM) vs. WT (7.4 ± 0.8 to 4.5 ± 0.8, p<0.05) and 49% reduction in Tie2‐sEH Tr treated with Ang II vs. Tie2‐sEH Tr (5.2 ± 0.4 to 2.7 ± 0.3, p<0.05, Fig. 1). Ang II also decreased repayment duration (min) by 49% in WT treated with Ang II vs. WT (2.5 ± 0.5 to 1.2 ± 0.4, p<0.05) and 54% in Tie2‐sEH Tr treated with Ang II vs. Tie2‐sEH Tr (1.7 ± 0.4 to 0.8 ± 0.2, p<0.05, Fig. 2). Peak repayment flow (ml/min/g) was also reduced by 11% in WT treated with Ang II vs. WT (36.0 ± 0.7 to 32.1 ± 1.4, p<0.05) and by 4% reduction in Tie2‐sEH Tr treated with Ang II vs. Tie2‐sEH Tr (32.2 ± 0.6 to 30.9 ± 1.5, p<0.05, Fig. 3). Furthermore, CF (ml/min/g) was reduced by 43% in WT treated with Ang II vs. WT (14.2 ± 0.5 to 8.2 ± 0.8, p<0.05) and by 31% in Tie2‐sEH Tr treated with Ang II vs. Tie2‐sEH Tr (12.1 ± 0.8 to 8.3 ± 1.2, p<0.05, Fig. 4). Heart Rate was not affected in either group. Our results demonstrate that Ang II reduces CRH in both WT and Tie2‐sEH Tr, but it decreases it more in Tie2‐sEH Tr compared to WT (p<0.05). These data suggest that Ang II‐induced negative effect on myocardial recovery from ischemic insult may further be aggravated by over‐expression of soluble epoxide hydrolase. Support or Funding Information Supported by HL‐114559 to MAN and z01‐ES025034 to DCZ.