title: Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats.
abstract: OBJECTIVE
  This study tested the hypothesis that overproduction of endogenous nitric oxide (NO) during endotoxemia may modulate coronary autoregulation and myocardial reactive hyperemia.
  
  
  METHODS
  Hearts of endotoxin-pretreated rats and controls were isolated and arranged for perfusion in a Langendorff preparation. Autoregulation was studied by examining flow-pressure relations during stepwise changes in perfusion pressure. The contribution of nitric oxide was examined by perfusion with N omega-nitro-L-arginine (NNLA), an inhibitor of nitric oxide synthesis and methylene blue (MB), an inhibitor of soluble guanylate-cyclase.
  
  
  RESULTS
  Endotoxin-treated hearts showed massive coronary vasodilatation and autoregulatory function was impaired at perfusion pressures from 20 to 60 mmHg. Both NNLA and MB reduced coronary flow, improved autoregulation and eliminated differences in coronary flow and autoregulation between the control and endotoxin-treated group. Vasoconstriction with vasopressin, a direct smooth muscle constrictor, could not eliminate differences in autoregulation between groups. Reactive hyperemia following coronary occlusion in endotoxin-treated hearts showed decreased duration, flow repayment and repayment ratio. In the presence of NNLA or MB, however, no significant differences in reactive hyperemic flow patterns were present.
  
  
  CONCLUSIONS
  These observations suggest that massive coronary vasodilatation due to increased myocardial NO synthesis can result in autoregulatory dysfunction and altered myocardial reactive hyperemia during endotoxemia.
authors.affiliation: Department of Surgery, University Hospital Rotterdam, Erasmus University Rotterdam, Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Avontuur
authors.forename: H A
authors.initials: HA
authors.lastname: Bruining
authors.forename: C
authors.initials: C
authors.lastname: Ince
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006706:Homeostasis; D006940:Hyperemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008751:Methylene Blue