Concerted actions of renal endothelial and macula densa NO systems in the maintenance of extracellular fluid volume.

It is now clear that nitric oxide (NO) exerts a substantial influence on renal function and that the kidney has a high capacity to produce NO. However, there are at least two different NO systems in the kidney. The interplay between NO generated by the endothelium and by the macula densa is considered in this review. It seems that endothelial NO increases in response to an increase in perfusion pressure and an increase in distal delivery, whereas macula densa NO decreases upon a sustained increase in distal delivery. Furthermore, evidence is accumulating that macula densa NO may well mediate renin release. Though seemingly in contrast, both the response of the endothelial NO and of the macula densa NO system seem appropriate to restore a perturbation of fluid balance. The function of the tubuloglomerular feedback (TGF) mechanism is likely to be influenced by both sources of NO, because of the close proximity of these NO producing cells to the vascular smooth muscle cells of the afferent arteriole. The endothelial NO system seems to be responsible for short-term, dampening actions to increased afferent arteriolar tone elicited by activation of the TGF system. The macula densa NO system, on the other hand, is probably adapting TGF responses to sustained increases in distal delivery. The analysis presented in this paper is an attempt to integrate the function of the two NO systems into physiological regulation. The exact role of the medullary NOS enzymes remains to be further elucidated.