CHRONIC INHIBITION OF NITRIC-OXIDE SYNTHASE IN HEYMANN NEPHRITIS

Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-N-G-nitroa rginine-methylester(L-NAME, 10 mg/100 mi in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of g uanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided int o the following groups: control, nephritis, L-NAME, and nephritis-L-NA ME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the n ephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05). L- NAME treatment alone did not have any effect on plasma ANP levels. Blo od pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L NAME group. No differences i n the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hyperte nsion and aggravates albuminuria in chronic nephritis. Moreover, nephr itis itself may decrease the production of cGMP either as a consequenc e of blunted NO activity or, in addition, because of ANP resistance. I t appears that NO synthase inhibition does not change the immunologica l course of Heymann nephritis but rather the increased hemodynamic loa d makes the course of nephritis worse.