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Angiotensin II Negatively Modulates Coronary Reactive Hyperemia and Deletion of Soluble Epoxide Hydrolase Partially Ameliorates 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.719.5
Subject(s) - epoxide hydrolase 2 , chemistry , medicine , angiotensin ii , endocrinology , reactive hyperemia , ischemia , endothelial dysfunction , renin–angiotensin system , vasodilation , enzyme , blood pressure , biochemistry
Impaired coronary reactive hyperemia (CRH) is associated with cardiovascular disease. Angiotensin II (Ang II) has powerful short‐ and long‐term effects on many organs including coronary endothelium. In 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. EETs level is increased in sEH KO vs. WT mice. Our previous data showed that CRH is increased in sEH KO vs. WT. We hypothesized that Ang II negatively modulates CRH and that deletion of sEH partially ameliorates its effect. Coronary flow (CF) in isolated sEH KO 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 32% reduction in sEH KO treated with Ang II vs. sEH KO (9.1 ± 0.2 to 6.2 ± 0.5, 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 47% in sEH KO treated with Ang II vs. sEH KO (2.4 ± 0.2 to 1.3 ± 0.3, 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 6% reduction in sEH KO treated with Ang II vs. sEH KO (35.5 ± 0.7 to 33.2 ± 1.4, 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 34% in sEH KO treated with Ang II vs. sEH KO (15.0 ± 0.7 to 9.8 ± 0.6, 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 sEH KO, but it decreases it more in WT compared to sEH KO (p<0.05). These data suggest that Ang II‐induced negative effect on myocardial recovery from ischemic insult may partially be protected by deletion of soluble epoxide hydrolase. Support or Funding Information HL‐114559 to MAN and z01‐ES025034 to DCZ