Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat.

1. The effects of the nitric oxide (NO) donors, S-nitroso-glutathione (SNOG) and S-nitroso-N-acetyl-penicillamine (SNAP), on the acute intestinal microvascular dysfunction induced by NG-nitro-L-arginine methyl ester (L-NAME) in combination with low doses of endotoxin were investigated in the anaesthetized rat. 2. Administration of L-NAME (5 mg kg-1, s.c.) concurrently with E. coli lipopolysaccharide (LPS, 3 mg kg-1, i.v.) provoked the leakage of radiolabelled albumin in the ileum and colon, as a measure of microvascular damage, determined 1 h after challenge. 3. Intravenous infusion of SNOG or SNAP (1-10 micrograms kg-1 min-1) dose-dependently attenuated the microvascular leakage induced by L-NAME and LPS. 4. Infusion of the lowest doses of SNOG or SNAP (1 microgram kg-1 min-1, i.v.) that significantly reduced the albumin leakage, did not affect the increase in blood pressure in response to L-NAME in LPS-treated rats. Higher doses of SNOG or SNAP (5-10 micrograms kg-1 min-1, i.v.) dose-dependently reduced this increase in blood pressure. 5. In control studies, intravenous infusion of glutathione (10 micrograms kg-1 min-1) or N-acetyl-penicillamine (10 micrograms kg-1 min-1) had no effect on microvascular leakage in the ileum and colon induced by LPS and L-NAME. 6. Pretreatment with rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p., 4 h before challenge), which reduced the neutrophil count in peripheral arterial blood, also inhibited the microvascular leakage in the ileum and colon.(ABSTRACT TRUNCATED AT 250 WORDS)