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Norepinephrine increases the angiotensin II response of interlobar arteries in a hypoxia/reperfusion model
Author(s) -
Patzak Andreas,
Fähling Michael,
Sendeski Mauricio,
Persson Pontus Börje,
Kaufmann Jana
Publication year - 2011
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.25.1_supplement.665.23
Subject(s) - prazosin , yohimbine , angiotensin ii , hypoxia (environmental) , endocrinology , medicine , agonist , chemistry , adrenergic receptor , receptor , pharmacology , antagonist , organic chemistry , oxygen
Sympathetic activation and ischemia/hypoxia are factors in the pathogenesis of acute renal injury. We test the hypothesis that norepinephrine (NE) increases the responsiveness of renal arteries to angiotensin II in a model of hypoxia/reperfusion. Isometric contraction was measured in rings of interlobar arteries of male mice. Concentration response curves for Ang II (10 −10 to 3*10 −7 mol/l) were obtained after 60 min of hypoxia with and without treatment with NE (10 −9 mol/l) or combination of NE with adrenergic receptor antagonists followed by 10 min reperfusion. Hypoxia/reperfusion alone reduced the Ang II response compared to the non‐hypoxic control. NE treatment during hypoxia increased Ang II response above the control level. Prazosin, Yohimbine or Propanolol alone did not inhibit the NE effect significantly. Combination of Prazosin and Yohimbine partially inhibited it, whilst combination of Prazosin, Yohimbine, and Propanolol did not. The beta3 agonist BRL37344 mimicked the NE effect. Western blotting showed increased phosphorylation of p38 MAPK and MLC (20) after hypoxia/reperfusion with NE and Ang II treatment. Also, the selective p38 MAPK inhibitor SB202190 blocked the NE effect. The study demonstrates that NE treatment during hypoxia affects Ang II responses after reperfusion via activation of several adrenergic receptors and including the p38 MAPK pathway.