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Redox‐Dependent Effects of Angiotensin II on Coronary Collateral Growth
Author(s) -
Rocic Petra,
Reed Ryan E,
Kolz Christopher
Publication year - 2007
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.21.5.a527-d
Subject(s) - angiotensin ii , oxidative stress , chemistry , candesartan , medicine , endocrinology , superoxide , redox , ischemia , vasodilation , receptor , biochemistry , enzyme , organic chemistry
AT1R blockers reportedly inhibit or promote angiogenesis. Since coronary collateral growth (CCG) is redox‐sensitive, we hypothesized that controversial effects of angiotensin II (AII) are due to boundaries of redox signaling which regulate CCG. We stimulated CCG in normal (WKY) and metabolic syndrome (JCR) rats by transient, repetitive ischemia (RI) for 10 days. Blood flow (microspheres, ml/min/g) was measured in normal (NZ) and collateral‐dependent (CZ) zones. In WKY, RI increased CZ flow (CZF) (0.13 to 0.84), but RI+sAII (subpressor dose of AII) increased CZF more (0.13 to 1.42). In contrast, a hypertensive dose of AII (hAII) decreased CZF compared to RI (0.12 to 0.69 [RI+hAII]). Candesartan also abrogated CZF in WKY (0.12 to 0.56). RI CZF in JCR was significantly decreased compared to WKY (0.09 to 0.12), and was associated with a large increase in superoxide (DHE). CZF in JCR was partially restored by candesartan (0.09 to 0.45), accompanied by reduction in superoxide comparable to WKY+RI. Activation of p38 was directly related to CCG; when non‐existent, there was no CCG. Thus, AII regulates CCG via optimal amounts of ROS and activation of redox‐sensitive signaling. With normal oxidative stress (WKY), AT1R blockade decreases p38 activation and RI‐induced CCG; with elevated basal oxidative stress (JCR), AT1R blockade rescues RI‐induced CCG, by normalizing oxidative stress and activating p38. Supported by P20RR18766 (PR).