[Paracrine kidney activity and homeostasis: the emergence of nitric oxide. A conceptual perspective].

In nephrology, intensive research has focused in recent years on the interplay between NO produced by the different isoforms of NO synthase (NOS) and complex renal functions. In this regard, the juxtaglomerular apparatus is of particular interest. First, it is the main site for control of renal blood flow by autoregulation and of glomerular filtration rate by tubuloglomerular feedback, as well as of renin secretion. Second, two constitutive NOS, nNOS and eNOS, are expressed, respectively, in the macula densa cells and in the endothelium of the afferent and efferent arteriole. It was thus not unexpected that NO could interact with the physiological variables. Indeed, NO attenuates rapidly the autoregulatory efficacy of renal blood flow as well as the sensitivity of the tubuloglomerular feedback by inhibiting Ca++ influx mainly in the afferent arteriole. On the other hand, renin secretion may be stimulated as well as inhibited by NO. These opposing effects, although as yet unexplained, could be related to the source of NO. If so, the hypothetical dual effect of NO could be secondary to a difference in modulation of each NOS isoform by their specific stimuli and results in secretion or not of renin. This hypothesis seems to be applicable to changes in extracellular volume.