Inducible nitric oxide synthase is involved in acid-induced gastric hyperemia in rats and mice

The role of different isoforms of nitric oxide synthase ( NOS) in the gastric mucosal hyperemia, induced by 155 mM luminal hydrochloric acid ( pH approximate to 0.8) without a barrier breaker, was investigated. Rats were anesthetized with Inactin ( 120 mg/kg ip), and mice were anesthetized with Forene (2.2% in 40% oxygen gas at 150 ml/min); the gastric mucosa was exteriorized. Gastric mucosal blood flow was measured with laser-Doppler flowmetry (LDF) in rats treated with N-omega-nitro-L-arginine (L-NNA; unspecific NOS inhibitor), L-N-6-(1-iminoethyl) lysine [ L-NIL; inducible (i) NOS inhibitor], or S-methyl-L-thiocitrulline [SMTC; neuronal (n) NOS inhibitor], 10 mg/kg, followed by 3 mg . kg(-1) . h(-1) iv, in iNOS-deficient (-/-) and nNOS(-/-) mice. mRNA was isolated from the gastric mucosa in iNOS(-/-) and wild-type (wt) mice, and real-time RT-PCR was performed. The effect of 155 mM acid on gastric mucosal permeability was determined by measuring the clearance of Cr-51-EDTA from blood to lumen. LDF increased by 48 +/- 13% during 155 mM HCl luminally, an increase that was abolished by L-NNA, SMTC, or L-NIL. In iNOS wt mice, LDF increased by 33 +/- 8% during luminal acid. The blood flow increase was attenuated substantially in iNOS(-/-) mice. RT-PCR revealed iNOS mRNA expression in the gastric mucosa in the iNOS wt groups. The blood flow increase in response to acid was not abolished in nNOS(-/-) mice (nNOS-sufficient mice, 39 +/- 18%; heterozygous mice, 25 +/- 19%; -/- mice, 19 +/- 7%). Mucosal permeability was transiently increased during 155 mM HCl. The results suggest that iNOS is constitutively expressed in the gastric mucosa and is involved in acid-induced hyperemia, suggesting a novel role for iNOS in gastric mucosal protection.