Effects of Nitric Oxide on Renal Proximal Tubular Na⁺Transport

Figures

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  Figure 1. Proximal tubular Na + reabsorption. Active Na+ transport mediated by basolateral NKA provides the driving force for proximal tubular Na+ transport. Transporters in the apical membrane include NHE3, SGLT, and NaPi2. NHE3 is considered to be responsible for most of the Na+ reabsorption from the glomerular filtrate. NBCe1 at the basolateral membrane plays an important role not only in Na+ homeostasis but also in the systemic acid/base balance. NKA, Na+/K+ ATPase; NHE3, Na+/H+ exchanger isoform 3; NBCe1, Na+/HCO3− cotransporter; Glu, glucose; SGLT, Na+/glucose cotransporter; NaPi2, Na+/phosphate cotransporter type 2.

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  Figure 2. Species difference in Ang II-mediated regulation of proximal tubular Na + transport. In humans, Ang II dose-dependently stimulates the NO/cGMP pathway via the AT1 receptor over a wide range of concentrations (from low to high). The signalling cascade phosphorylates ERK, resulting in the stimulation of proximal tubular Na+ reabsorption, although the interplay between Ang II and NO signalling pathway on the NKA activity is still unconfirmed. In animal proximal tubules (mice, rats, and rabbits), a high concentration of Ang II also stimulates the NO/cGMP pathway, but the subsequent signalling cascade activates cGKII to exert inhibitory effects on Na+ reabsorption. As for NHE3, the inhibitory effect of Ang II is involved in the cGMP-dependent protein kinase, which is independent of the NO/cGMP pathway. Ang II, angiotensin II; AT1, angiotensin II receptor type 1; NO, nitric oxide; cGMP, guanosine 3′,5′-cyclic monophosphate; ERK, extracellular signal-regulated kinase; cGKII, cGMP-dependent protein kinase type II; NKA, Na+/K+ ATPase; NHE3, Na+/H+ exchanger isoform 3; NBCe1, Na+/HCO3− cotransporter.