PRESSOR AND VASOCONSTRICTOR EFFECTS OF METHYLENE-BLUE IN ENDOTOXAEMICRATS

Nitric oxide (NO) is a primary mediator uf hypotension in sepsis. We e xamined the effects of methylene blue (MB), an inhibitor oi the NO/cGM P pathway, on mean arterial pressure (MAP). cardiac output (CO). total peripheral resistance (TPR), mesenteric blood flow (MBF) and renal bl ood flow (RBF) In pentobarbitone-anaesthetised rats injected with lipo polysaccharide (LPS, 7.5 mg/kg), MB (1, 3 or 10 mg/kg.h) or vehicle wa s 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 salin e. LPS reduced MAP, CO, RBF as well as MBF at 2.5 and 4 h, and increas ed 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 TP R 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 wa s 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 no t raise MAP but increases TPR and reduces CO.