Early phase microvascular interactions in rat jejunum between nitric oxide and vasopressin following indomethacin administration

Abstract

The involvement of endogenous vasopressin in the actions of indomethacin following the concurrent administration of the nitric oxide (NO) synthase inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME), on acute intestinal microvascular permeability has been investigated in the rat. Administration of indomethacin (10 mg/kg, s.c.) or L‐NAME (10 mg/kg, s.c.) alone did not affect jejunal and ileal vascular permeability after 1 h, as determined by the leakage of radiolabelled serum albumin. In contrast, when indomethacin (10 mg/kg, s.c.) was injected concurrently with L‐NAME (2–10 mg/kg, s.c.), significant dose‐dependent plasma leakage occurred in the jejunum. Pretreatment with L‐arginine (300 mg/kg s.c.) 15 min prior to L‐NAME prevented these changes in microvascular permeability. Moreover, pretreatment with the vasopressin pressor‐receptor antagonist, d(CH2)5Tyr(Me)AVP (0.01– 0.2 μg/kg, s.c.) dose‐dependently attenuated such damage. These findings suggest that following indomethacin administration, the early inhibition of NO synthase leads to acute microvascular injury involving vasopressin in the rat jejunum. This suggests a protective role of NO, formed by constitutive NO synthase, counteracting effectively the deleterious actions of endogenous vasopressin.