Pressor and vasoconstrictor effects of methylene blue in endotoxaemic rats.
Nitric oxide (NO) is a primary mediator of hypotension in sepsis. We examined the effects of methylene blue (MB), an inhibitor of the NO/cGMP pathway, on mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), mesenteric blood flow (MBF) and renal blood flow (RBF) in pentobarbitone-anaesthetised rats injected with lipopolysaccharide (LPS, 7.5 mg/kg). MB (1, 3 or 10 mg/kg x h) or vehicle was i.v. infused into four groups at 2.5 h after i.v. injection of LPS. Two other groups received MB or vehicle at 2.5 h after receiving saline. LPS reduced MAP, CO, RBF as well as MBF at 2.5 and 4 h, and increased TPR at 2.5 but not 4 h. Whereas MB alone had no effects on measured variables in control rats at 4 h, in LPS-treated rats, it elevated TPR at all doses and attenuated the fall in MAP at the two low doses. CO was unaltered by low doses of MB but reduced by the high dose. MBF was unaltered, but RBF was increased by the lowest dose but decreased by the highest dose of MB. Therefore, in endotoxaemia, a low dose of MB increases MAP and TPR but does not alter CO; a high dose of MB does not raise MAP but increases TPR and reduces CO.
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D019446:Endotoxemia / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004731:Endotoxins; D006993:Hypnotics and Sedatives; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; C044101:endotoxin, Escherichia coli; D010424:Pentobarbital; D008751:Methylene Blue