Role of nitric oxide in endotoxin-induced metabolic and vascular dysregulation of the canine diaphragm.
We assessed the role of nitric oxide (NO) in the regulation of diaphragmatic O2 uptake (Vo2di) and phrenic vascular resistance during endotoxemia in anesthetized, mechanically ventilated dogs. Left diaphragmatic vasculature was isolated and briefly pump perfused with arterial blood at a normal flow rate, at a high rate (50% higher than normal), and at low rat (60 to 70% lower than normal). At each rate, Vo2di and phrenic perfusion pressure (Pphr) were measured. Escherichia coli endotoxin (100 mg) was infused intravenously over 90 min in several groups of animals, whereas normal saline was infused into the other. Endotoxin infusion increased Vo2di and reduced Pphr at a given flow rate. These parameters remained unchanged in the saline-infused animals. Infusion of NG-nitro-L-arginine methyl ester (LNAME 6 x 10(-4) M) into the phrenic artery of the endotoxin group reversed the decline in Pphr with no effect on Vo2di. LNAME infusion in the saline group increased Pphr at normal and high flow rates only. Single intravenous injections of LNAME increased arterial pressure and reduced cardiac output in endotoxemic animals, whereas only an increase in arterial pressure was observed in saline-infused animals. Serum arterial and phrenic venous NO concentrations measured in separate groups of animals increased significantly after endotoxin infusion, whereas saline infusion had no effect on these parameters. These results indicate that enhanced NO release plays a significant role in endotoxin-induced phrenic and systemic vasodilation. However, the increase in Vo2di in the endotoxin group does not seem to be mediated by NO release.
Hussain
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Critical Care Division, Royal Victoria Hospital, Montreal, Quebec, Canada.
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003964:Diaphragm / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004731:Endotoxins / Q000009:adverse effects* / Q000097:blood; D004926:Escherichia coli; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation
D004731:Endotoxins; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester