Predicting Sex Differences in the Effects of Diuretics in Renal Epithelial Transport during Angiotensin II-induced Hypertension

Am J Physiol Renal Physiol. 2024 Mar 14. doi: 10.1152/ajprenal.00398.2023. Online ahead of print.ABSTRACTChronic angiotensin II (AngII) infusion is an experimental model that induces hypertension in rodents. The natriuresis, diuresis, and blood pressure responses differ between males and females. This is perhaps not unexpected, given the rodent kidney, which plays a key role in blood pressure regulation, exhibit marked sex differences. Under normotensive conditions, compared to males, the female rat nephron exhibits lower Na+/H+ exchanger 3 (NHE3) activity along the proximal tubule, but higher Na+ transporter activities along the distal segments. AngII infusion-induced hypertension induces a pressure natriuretic response that reduces NHE3 activity and shifts Na+ transport capacity downstream.The goals of this study are to apply a computational model of epithelial transport along a rat nephron (i) to understand how a 14-day AngII infusion impacts segmental electrolyte transport in male and female rat nephrons, and (ii) to identify and explain any sex differences in the effects of loop diuretics, thiazide diuretics, and K+-sparing diuretics. Model simulations suggest that the NHE3 downregulation in the proximal tubule is a major contributor to natriuresis and diuresis in hypertension, with the effects stronger in males. All three diuretics are predicted to induce stronger natriuretic and diuretic effects under hypertension compared to normotension, with the relative increases i...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Source Type: research