NITRIC-OXIDE SYNTHETIC PATHWAY AND REGULATION - ITS POTENTIAL ROLE INIMMUNE AND INFLAMMATORY REACTIONS IN THE GLOMERULUS

Nitric oxide (NO) is a free radical synthesised by nitric oxide syntha se from L-arginine by a family of nitric oxide synthase (NOS) enzymes. It is involved in vasodilatation, neurotransmission and is a mediator of macrophage cytotoxicity. One of the isoforms of NOS (iNOS) is indu ced in a wide range of cells by inflammatory cytokines and may synthes ise large quantities of NO over many hours. There is strong evidence f or the involvement of NO in glomerulonephritis. Isolated nephritic glo meruli synthesise nitrite, the stable end product of NO, and iNOS mRNA and protein are present. Infiltrating macrophages are a major source of glomerular NO but mesangial cells also possess an inducible iNOS. T he role of this versatile molecule in glomerulonephritis remains to be clarified with evidence both for a beneficial role, possibly through improvement in glomerular blood flow and scavenging superoxide anion, and for a harmful effect possibly by direct toxicity.