title: The renin-angiotensin system does not contribute to the endothelial dysfunction and increased infarct size in rats exposed to second hand smoke.
abstract: BACKGROUND
  Both second hand smoke (SHS) and the renin-angiotensin system (RAS) contribute to endothelial dysfunction and increased infarct size in a rat ischaemia-reperfusion model. However, the potential interaction between SHS and the RAS is unknown.
  
  
  METHODS
  Eighty-four rats were randomised into four groups: group C was a normal control; L was given 40 mg/kg/day of losartan in drinking water; SC and SL were exposed to SHS (smoking chamber) and given regular water or 40 mg/kg/day of losartan in drinking water, respectively. After six weeks of pre-treatment, rats were subjected to 17 minutes of left coronary artery occlusion and 2 hours of reperfusion with haemodynamic and ECG monitoring.
  
  
  RESULTS
  Haemodynamics were not significantly different among the four groups. Losartan increased the threshold for ventricular fibrillation (p=0.0001) and reduced spontaneous ventricular arrhythmias (p=0.002) during ischaemia-reperfusion, while SHS did not (p=0.713, 0.110), and there was no interaction between losartan and SHS. The maximal endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased by losartan (p=0.007). Myocardial infarct size was smaller in the losartan groups (p=0.032), larger in the SHS groups (p=0.0001), and there was no significant interaction.
  
  
  CONCLUSIONS
  In conclusion, losartan decreased infarct size and increased endothelium-dependent vasorelaxation. SHS exposure impaired endothelial function and increased infarct size. The effects of losartan and SHS were consistently independent of each other. These results suggest that the RAS does not contribute to the adverse effects of SHS.
authors: Department of Medicine, University of California, San Francisco 94143-0124, USA.
authors: Bo-qing
authors: BQ
authors: Zhu
authors: Richard E
authors: RE
authors: Sievers
authors: Amanda E M
authors: AE
authors: Browne
authors: Robert T
authors: RT
authors: Hillman
authors: Kamel
authors: K
authors: Chair
authors: Randall J
authors: RJ
authors: Lee
authors: Kanu
authors: K
authors: Chatterjee
authors: Stanton A
authors: SA
authors: Glantz
authors: William W
authors: WW
authors: Parmley
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009538:Nicotine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D014028:Tobacco Smoke Pollution; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000804:Angiotensin II; D009538:Nicotine; D012083:Renin; D019808:Losartan