Premium
HYPOXIA INDUCIBLE FACTOR‐1 IMPROVES THE ACTIONS OF NITRIC OXIDE AND NATRIURETIC PEPTIDES AFTER SIMULATED ISCHEMIA‐REPERFUSION
Author(s) -
Weiss Harvey R,
Luciano Jason A,
Tao Tan,
Zhang Qihang,
Huang Emily,
Scholz Peter M
Publication year - 2008
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.22.1_supplement.750.1
Subject(s) - deferoxamine , snap , medicine , cgmp dependent protein kinase , myocardial stunning , protein kinase a , nitric oxide , endocrinology , stunning , ischemia , hypoxia (environmental) , phosphorylation , chemistry , biochemistry , oxygen , mitogen activated protein kinase kinase , computer graphics (images) , computer science , organic chemistry
We tested the hypothesis that upregulation of hypoxic inducible factor‐1 (HIF‐1) would improve the negative functional actions of cyclic GMP in rabbit cardiac myocytes subjected to simulated ischemia [15 min 95% N 2 ‐5% CO 2 ]‐reperfusion [reoxygenation] to produce stunning. HIF‐1α was increased with deferoxamine (150 mg/kg/2 days). Shortening was examined after brain natriutetic peptide (BNP, 10 −8 , 10 −7 M) or S‐nitroso‐N‐acetyl‐penicillamine (SNAP, 10 −6 , 10 −5 M) and KT5823 (cGMP protein kinase inhibitor, 10 −6 M). In controls, BNP (−30%) and SNAP (−41%) reduced percent shortening, while KT5823 partially restored function (+18%). Deferoxamine‐control myocytes responded similarly. After stunning, BNP (−21%) and SNAP (−25%) reduced shortening less and KT5823 did not increase function (+2%). Deferoxamine increased the effects of BNP (−38%) and SNAP (−41%) in stunning and restored the KT5823 effect (+12%). The cGMP protein kinase increased protein phosphorylation in controls. Phosphorylation was reduced in stunning and restored after deferoxamine. Thus, ischemia‐reperfusion reduced the effects of cGMP and this was related to reduced cGMP protein kinase action. Increased HIF‐1α protects the functional effects of cGMP thorough maintenance of cGMP protein kinase activity after ischemic‐reperfusion.