CONSEQUENCES OF ACUTE NITRIC-OXIDE SYNTHESIS INHIBITION IN EXPERIMENTAL GLOMERULONEPHRITIS

To assess the functional relevance of the enhanced glomerular nitric o xide (NO) synthesis during acute nephrotoxic serum (NTS) nephritis, a NO synthesis inhibitor (NOI) N(G)-monomethyl-L-arginine was administer ed to normal (N + NOI) and acutely nephritic (NTS + NOI) Munich-Wistar rats, and systemic and glomerular hemodynamic responses were contrast ed with those observed in vehicle-treated normal and nephritic (NTS) c ontrols. Urinary protein excretion rates were equal in normal and N NOI rats but were markedly elevated in NTS animals and further increas ed in NTS + NOI. NO inhibition in normal animals (normal versus N + NO I) led to reductions in glomerular plasma flow rate and the glomerular capillary ultrafiltration coefficient (K(f)) and elevations in affere nt and efferent arteriolar resistances and net transcapillary hydrauli c pressure difference (DELTAP), as well as an increase in systemic art erial pressure. The increase in DELTAP offset the falls in glomerular plasma flow rate and K(f), and GFR was preserved. Directionally simila r responses in efferent resistance occurred in NTS + NOI compared with NTS, however, afferent resistance was not further affected by NOI. Ad ditionally, although K(f) was severely depressed in the NTS group (app roximately 60% versus normal), it was not further depressed by NOI tre atment. Polymorphonuclear cell (PMN) infiltration/glomerulus was mildl y increased in N + NOI over normal. In contrast, PMN number in NTS + N OI rats was diminished as compared with NTS. Thus, NO inhibition durin g inflammatory glomerular injury leads to a dramatic increase in prote inuria, likely as the result of marked exacerbation of the already ele vated values of DELTAP. Moreover, tonic release of NO plays a crucial role in the maintenance of baseline vascular resistance and K(f) in no rmal glomeruli, but to a lesser extent in acutely inflamed glomeruli. The apparent amelioration of PMN infiltration in NTS + NOI rats remain s unexplained but may be related to the severe fall in nephron perfusi on.