title: The mechanistic basis for the disparate effects of angiotensin II on coronary collateral growth.
abstract: OBJECTIVE
  We hypothesize that controversial effects of angiotensin II (Ang II) are attributable to its regulation of reactive oxygen species (ROS) and ROS-dependent signaling.
  
  
  RESULTS
  Coronary collateral growth (CCG) was stimulated in normal (WKY) and syndrome X (JCR) rats by transient/repetitive ischemia (RI). Blood flow was measured in the normal (NZ) and the collateral-dependent (CZ) zone. In WKY, RI increased CZ flow (0.84 mL/min/g), but RI+subpressor Ang II increased it more (1.24 mL/min/g). This was associated with transient p38 and sustained Akt activation. A hypertensive dose of Ang II decreased CZ flow (0.69 mL/min/g), which was associated with sustained p38 and transient Akt activation. AT1R blockade by candesartan abrogated CZ flow in WKY (0.58 mL/min/g), reduced myocardial superoxide, and blocked p38 and Akt activation. RI-induced CZ flow in JCR was significantly decreased compared with WKY (0.12 mL/min/g), associated with a large increase in superoxide and lack of p38 and Akt activation. CZ flow in JCR was partially restored by candesartan (0.45 mL/min/g), accompanied by reduction in superoxide and partial restoration of p38 and Akt activation.
  
  
  CONCLUSIONS
  Ang II/AT1R blockade, at least in part, regulates CCG via generating optimal ROS amounts and activating redox-sensitive signaling.
authors.affiliation: Department of Integrative Medical Sciences, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44275, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Reed
authors.forename: Christopher
authors.initials: C
authors.lastname: Kolz
authors.forename: Barry
authors.initials: B
authors.lastname: Potter
authors.forename: Petra
authors.initials: P
authors.lastname: Rocic
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D054059:Coronary Occlusion / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D018056:Hemorheology; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II