Sex-Differences in Solute Transport Along the Nephrons: Effects of Na+ Transport Inhibition.

Sex-Differences in Solute Transport Along the Nephrons: Effects of Na+ Transport Inhibition. Am J Physiol Renal Physiol. 2020 Aug 03;: Authors: Hu R, McDonough AA, Layton AT Abstract Each day approximately 1.7kg of NaCl and 180L of water are reabsorbed by nephron segments in humans, with urinary excretion fine-tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na+ transporters. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and how those effects may vary between males and females. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes along the nephrons of the male and female rat kidneys. We simulated the inhibition of the Na+/H+ exchanger (NHE3), the bumetanide-sensitive Na+-K+-2Cl- transporter (NKCC2), the Na+-Cl- cotransporter (NCC), and the amiloride-sensitive Na+ channel (ENaC). NHE3 inhibition simulations predict a substantially reduced proximal tubule TNa and NKCC2 inhibition substantially reduces thick ascending limb TNa. Both give rise to diuresis, natriuresis, and kaliuresis, with those effects stronger in females. While NCC inhibition is predicted to have only minor impact on renal TNa, it nonetheless has a notable effect of enhancing the excretion of Na+, K+, and Cl-, particularly ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research