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Interaction of protease‐activated receptor 2 with chronic angiotensin II‐induced endothelial dysfunction in mice
Author(s) -
McGuire John,
Hughes Keon,
Halfyard Sarah,
Wijekoon Enoka
Publication year - 2009
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.23.1_supplement.1017.15
Subject(s) - angiotensin ii , endocrinology , medicine , chemistry , vasodilation , endothelium , endothelial dysfunction , acetylcholine , sodium nitroprusside , mesenteric arteries , agonist , knockout mouse , saline , receptor , renin–angiotensin system , pharmacology , nitric oxide , blood pressure , artery
Protease‐Activated Receptor 2 (PAR‐2) knockout mice exhibit a different time course in blood pressure response to angiotensin II (AngII). In this study we measured endothelium‐dependent relaxations of mesenteric arteries from PAR‐2 knockout (PAR‐2 ‐/‐) and C57BL/6 mice using wire myographs. Our goal was to test the influence of PAR‐2 ‐/‐ on AngII‐induced endothelial dysfunction. Chronic AngII infusion of C57BL/6 and PAR‐2 ‐/‐ decreased acetylcholine (ACh)‐induced relaxations by ~20 % whereas PAR‐2 agonist (2fly) and sodium nitroprusside relaxations were unchanged relative to saline infusion groups. ACh‐induced relaxations of AngII‐PAR‐2 ‐/‐ arteries, but not AngII‐C57BL/6 arteries, were rescued in the presence of the cyclooxygenases inhibitor indomethacin. In contrast to these effects, indomethacin decreased the sensitivity to ACh in saline‐PAR‐2 ‐/‐ and did not affect either ACh‐ or 2fly‐induced relaxations in saline‐C57BL/6. The sensitivity to 2fly of arteries from AngII‐C57BL/6 was decreased in the presence of indomethacin. A combination of PAR‐2 gene knockout and indomethacin rescued ACh‐induced relaxations of vascular smooth muscle after chronic AngII infusion in mice. Cyclooxygenases contribute to the mechanism of persistent PAR‐2 vasodilation despite endothelial dysfunction and to the mechanism of action for ACh in PAR‐2 ‐/‐ mice. Funding sources: CIHR, IRIF, CFI.