Nitric oxide in the regulation of renal blood flow

Nitric oxide (NO.) is a simple molecule, synthesized from the amino acid L-arginine by a family of enzymes, NO. synthase (NOS). The L-arginine-NO. pathway plays a dominant role in the control of renal function under various physiologic and pathologic conditions. NO. is continuously released by the endothelium, and controls the tone of the glomerular afferent arteriole by modulating myogenic response and the action of various vasoconstrictors. On the other hand, NO. produced by the macula densa controls glomerular hemodynamics indirectly through tubuloglomerular feedback and renin release. It appears that NO. is also involved in medullary circulation and tubular function and, therefore, pressure natriuresis. Thus, the L-arginine-NO. pathway seems to play an important role in sodium hemostasis. Under certain pathologic conditions, NOS may be induced in the endothelial, vascular smooth muscle, mesangial, and tubular epithelial cells, and in macrophages, producing a large amount of NO., which may contribute to progression of renal disease. In acute renal failure, endogenous NO. seems to have a protective role against renal damage, as the inhibition of NOS aggravates renal dysfunction and histology. Although dietary L-arginine supplementation has been shown to protect against progression of renal damage, clarification of the exact role of NO. and the mechanism of L-arginine's beneficial effects must await further investigation. Finally, the recent development of targeting specific NOS isoforms or tissue may help clarify the role of the L-arginine-NO pathway in various physiologic and pathologic conditions, leading to the development of new therapeutic modalities.