THE ROLE OF NITRIC-OXIDE IN THE REGULATION OF MACROMOLECULAR TRANSPORT IN RAT JEJUNUM

1. Nitric oxide is known to affect epithelial and microvascular permea bility and is a major non-adrenergic non-cholinergic neurotransmitter in the intestine. We have previously demonstrated neuronal regulation of macromolecular transport in the intestine. To define this regulatio n further the role of nitric oxide was investigated. 2. Stripped rat j ejunum was mounted in Ussing chambers exposing the mucosal surface to bovine serum albumin (BSA; 2 mg ml(-1)), or BSA (2 mg ml(-1)) plus [I- 125]BSA (10 mu Ci). Following a 50 min equilibration, serosal fluids w ere sampled for four 10 min periods, and fluxes determined for intact BSA by enzyme-linked immunosorbent assay (ELISA) and total BSA by [I-1 25]BSA under basal conditions, and after treatment with N-G-nitro-L-ar ginine-methyl ester (L-NAME) alone or in conjunction with L-arginine o r decarboxylated molsidomine (SIN 1). 3. L-NAME significantly increase d intact BSA uptake. Total (intact + degraded) BSA flux was not altere d. The L-NAME effect was reversed by L-arginine and SIN 1. Additional experiments were performed by adding the nitric oxide donors sodium ni troprusside and SIN 1 directly to control tissue. Nitric oxide donors did not further decrease intact BSA flux below levels obtained from co ntrol tissue. The L-NAME enantiomer D-NAME had no effect. Sodium-free bathing solutions also had no effect on intact BSA uptake. Non-specifi c permeability, as assessed by the serosal to mucosal movement of [Cr- 51]ethylene-diamine-tetraacetate ([Cr-51]EDTA), was decreased with L-N AME. 4. The findings indicate that nitric oxide downregulates intact m acromolecular flux in the small intestine.