© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats
aDepartment of Surgery, University Hospital Rotterdam, Erasmus University Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands
bDepartment of Anesthesiology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
* Corresponding author. Tel.: +31 (10) 4639222; fax: +31 (10) 4635307.
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
-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.
KEYWORDS Nitric oxide; Autoregulation; Reactive hyperemia; Sepsis; N-Nitro-L-arginine; Methylene blue; Rat, heart
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