Effects of Nitric Oxide on Renal Proximal Tubular Na⁺Transport

Abstract

Nitric oxide (NO) has a wide variety of physiological functions in the kidney. Besides the regulatory effects in intrarenal haemodynamics and glomerular microcirculation, in vivo studies reported the diuretic and natriuretic effects of NO. However, opposite results showing the stimulatory effect of NO on Na+ reabsorption in the proximal tubule led to an intense debate on its physiological roles. Animal studies have showed the biphasic effect of angiotensin II (Ang II) and the overall inhibitory effect of NO on the activity of proximal tubular Na+ transporters, the apical Na+/H+ exchanger isoform 3, basolateral Na+/K+ ATPase, and the Na+/HCO3− cotransporter. However, whether these effects could be reproduced in humans remained unclear. Notably, our recent functional analysis of isolated proximal tubules demonstrated that Ang II dose-dependently stimulated human proximal tubular Na+ transport through the NO/guanosine 3′,5′-cyclic monophosphate (cGMP) pathway, confirming the human-specific regulation of proximal tubular transport via NO and Ang II. Of particular importance for this newly identified pathway is its possibility of being a human-specific therapeutic target for hypertension. In this review, we focus on NO-mediated regulation of proximal tubular Na+ transport, with emphasis on the interaction with individual Na+ transporters and the crosstalk with Ang II signalling.

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

“…; and (3) Can the vascular and/or tubular architecture influence the observations? All NOS isoforms are expressed in the kidney,38 and the synthesized NO itself is known to inhibit reabsorption of Na + along the nephron by reducing the respiratory rate of mitochondria8, 39, 40, 41 therefore, NO inhibits oxygen consumption. Three lines of evidence support our observations.…”

Regulation of Nitric Oxide Production in the Developmental Programming of Hypertension and Kidney Disease

“…First, hypertension and kidney disease have been associated with increased expression/activity of sodium transporters and enhanced sodium reabsorption [8,15]. NO has an inhibitory effect on the activity of several sodium transporters [79]. Thus, it is speculated that NO deficiency may fail to counterbalance the impaired sodium transporters induced by early-life insults, thus leading to programmed hypertension.…”

Synthesis, physicochemical characterisation and biological activity of anandamide/ɛ‐polycaprolactone nanoparticles obtained by electrospraying

“…In addition to the physicochemical characterisation of the Nps-AEA/PCL obtained, we carried out in vitro biological activity tests as the quantification of iNOS expression in human proximal tubular epithelial cells. It is known that this inducible isoform of NOS is widely expressed in cells of the renal proximal tubule [42]. To highlight, several studies have reported on a promising antihypertensive effect (primarily vasodilator) of AEA mediated by NO release in different cell types [43][44][45].…”