Inhibition of the synthesis of prostaglandins or nitric oxide at supraspinal or spinal level induces different actions on experimental gastric mucosal damage

The role of central nervous system in maintaining gastric mucosal integrity has been intensively studied in the last decade. Our previous findings suggest that activation of central (supraspinal) α2 adrenergic and opioid receptors result in gastric mucosal protection, since different opioid peptides and α2 adrenoceptor agonists given intracerebroventricularly (icv.) resulted in gastric mucosal protection against different types of gastric mucosal damage. Central nitric oxide is likely to be involved in mediation of gastroprotective effect, since inhibition of NO synthase by ice administration of NG-nitro-L-arginine aggravated the mucosal damage induced by ethanol and antagonized both the opioid- and α2 adrenoceptor mediated gastro-protective effect. The question was raised: whether spinal nitric oxide, which has a prominent role in mediation of spinal transmission of nociceptive stimuli, has any role in gastric mucosal integrity.

Methods: Gastric mucosal damage was induced by acidified ethanol and the lesions were examined 60min after ethanol challenge. The drugs under study were injected either acutely intracerebrventricularly (icv.) (10µl/rat) or intrathecally (it.) in (5µl/rat) through a polyethylene tube inserted 48h prior to the ulcer experiments.

Results and discussion: L-NNA in the dose of 0.23 and 0.46µmol/rat it. resulted in 44% and 78% inhibition of gastric mucosal damage. Similarly also indomethacin exerted a dose-dependent inhibition given it. in the doses of 0.56 and 1.4µmol/rat it. The same dose of L-NNA or indomethacin given icv. either failed to affect or aggravated the ethanol-induced lesions. These findings suggest an opposite role of spinal and supraspinal endogenous NO and prostaglandins in maintaining the integrity of gastric mucosa.

The work was supported by ETT 389/2003 and National Research and Technology, Hungary.