title: Angiotensin II type 1 receptor antagonist protects ventricular and coronary endothelial function after 24-hour heart preservation.
abstract: BACKGROUND
  Angiotensin II type 1 (AT1) receptor antagonists may enhance the cyclic guanosine monophosphate-nitric oxide system and thereby attenuate ventricular and coronary endothelial dysfunction after heart preservation.
  
  
  METHODS
  We used an isolated rabbit heart preparation perfused with blood from a support rabbit. The rabbit heart was excised, stored for 24 hours, and then perfused with blood from a support rabbit that was treated with an AT1 receptor antagonist (telmisartan; 5 mg/kg) or solvent. We evaluated the cardiac output with the working preparation, and coronary blood flow and coronary endothelial function with the Langendorff preparation. In addition, we measured the serum nitric oxide level in the coronary effluent.
  
  
  RESULTS
  The Telmisartan Group showed higher plasma angiotensin II levels (928.6 +/- 136.2 vs 271.6 +/- 81.6 pg/ml, p < 0.01), better cardiac output (116.2 +/- 5.4 vs 88.8 +/- 7.1 ml/min, p < 0.05), and higher coronary blood flow (25.0 +/- 2.2 vs 14.9 +/- 1.3 ml/min, p < 0.01). The coronary blood flow in response to acetylcholine was higher in the Telmisartan Group (47.8 +/- 3.9 vs 28.0 +/- 2.1 ml/min, p < 0.01), but there was no difference in response to sodium nitroprusside. The Telmisartan Group showed higher serum nitric oxide levels in the coronary effluent (33.9 +/- 4.6 vs 20.6 +/- 3.3 mumol/liter, p < 0.05).
  
  
  CONCLUSIONS
  Treatment with the AT1 receptor antagonist improved ventricular and endothelial function after 24-hour heart preservation. These data imply that AT1 activation plays a critical role in reperfusion injury. AT1 receptor blockade may be a promising strategy for long-term heart preservation.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kajihara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nishida
authors.forename: Noriko
authors.initials: N
authors.lastname: Boku
authors.forename: Hideki
authors.initials: H
authors.lastname: Tatewaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Eto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Morita
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D003331:Coronary Vessels; D003402:Creatine Kinase / Q000097:blood; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation; D007036:Hypothermia, Induced; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D000077333:Telmisartan; D014664:Vasodilation; D016276:Ventricular Function
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009569:Nitric Oxide; D003402:Creatine Kinase; D000077333:Telmisartan