title: Alterations in coronary artery vascular reactivity of hypertensive Ren-2 transgenic rats.
abstract: BACKGROUND
  The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats.
  
  
  RESULTS
  Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229 +/- 6 mm Hg; adult, 239 +/- 8 mm Hg) than in control rats (young, 126 +/- 2 mm Hg; adult, 118 +/- 3 mm Hg; P < .005). N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-7) to 10(-4) mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52 +/- 8% of the contraction to 100 mmol/L KCl; adult, 40 +/- 8%) but not aortas (young, 3 +/- 1%; adult, 2 +/- 1%). In coronary arteries, this response was significantly smaller in adult (n = 9) than in young (n = 8, P < .05) control rats. Young transgenic rats (56 +/- 9%, n = 8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6 +/- 3%, n = 7; P < .05 versus adult control rats; P < .01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10(-9) to 10(-4) mol/L) were totally blocked by L-NAME (10(-4) mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10(-7) mol/L). This stimulated release of EDNO, endothelium-independent relaxations in response to the nitrovasodilator linsidomine (10(-9) to 10(-5) mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats.
  
  
  CONCLUSIONS
  Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium-dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected.
authors.affiliation: Department of Research, University Hospital Basel, Switzerland.
authors.forename: M R
authors.initials: MR
authors.lastname: Tschudi
authors.forename: G
authors.initials: G
authors.lastname: Noll
authors.forename: U
authors.initials: U
authors.lastname: Arnet
authors.forename: D
authors.initials: D
authors.lastname: Novosel
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester