The role of renal proximal tubule transport in the regulation of blood pressure

The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT(1A) receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.

Altered Regulation of NHE3, NBC1 and Nitric Oxide System in the Kidney of Rats with Maleic Acid-nduced Metabolic Acidosis / 대한신장학회잡지

PURPOSE: The present study was aimed to determine whether there exist an altered regulation of tubular transporters and nitric oxide system in the kidneys in maleic acid-nduced metabolic acidosis. METHODS: Male Sprague-awley rats were treated with maleic acid (2 mmol/kg, every 24 hours, intraperitoneally) for 2 days. Control rats were injected with saline. At 24 hours following the second injection, rats were killed by decapitation. Plasma HCO3-and anion gap were measured. The protein expression of type 3 Na+/H+ exchanger (NHE3), type 1 Na+:HCO3- cotransporter (NBC1), and aquaporin (AQP)-1 in the cortex of the kidneys was determined by Western blot analysis. In addition, the expression of isoforms of nitric oxide synthase (NOS) was determined. Contents of nitric oxide metabolites (nitrite/ nitrate, NOx) were also measured in urine by colorimetric assay. RESULTS: Plasma concentrations of HCO3- were significantly decreased following the treatment of maleic acid, while plasma anion gap was did not differ between the experimental and the control groups. In the experimental group, the protein expression of NHE3 was significantly increased in the cortex of the kidney although the expression of NBC1 was not altered significantly. The expression of inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) was significantly increased in the cortex of the kidney. Accordingly, urine NOx contents were increased in the experimental group. In contrast, the expression of AQP1 was not altered. CONCLUSION: These results indicated that upregulation of NHE3 and nitric oxide system may play a role in regulation of acid-ase balance.