# Pressure Natriuresis and Renal Na+ Transporter Regulation in Males and Females: Impact of Diabetes with Hypertension

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $45,520

## Abstract

PROJECT SUMMARY
 Chronic kidney disease (CKD) is the gradual decline in the kidneys capacity to filter excess fluid
and waste from our blood. The main risk factors for CKD are high blood pressure (BP) and type 2
diabetes mellitus (T2D), which account for 73% of all CKD cases. Furthermore, 50-75% of all T2D
patients will develop hypertension (HTN). The kidneys play a central role in blood pressure regulation
through establishment of an individual’s BP set point. Pre-menopausal women have lower BP set
points and lower incidence of cardiovascular disease (CVD) compared to age-matched males. This
“female advantage” is also evident in milder phenotypes and slower disease progression observed in
HTN, CVD and diabetic kidney disease (DKD) compared to males. Mechanisms accounting for this
female advantage remain an important gap in our understanding of renal physiology. The overall
goals of this proposal are to define sexual dimorphisms in key renal homeostatic mechanisms that
impact BP, DKD and CVD using acute and chronic models of HTN in order to reduce incidence and
improve therapeutics.
AIM 1: Determine mechanisms and tubular locations responsible for the greater acute
pressure natriuresis response in F vs M SD rats. I will utilize classic surgical procedures to
increase blood pressure by vascular constriction to define sex-specific physiological responses and
Na+ transporter regulation along the nephron. These experiments will provide insights into the
mechanisms of the female advantage.
AIM 2: Define the sexual dimorphisms in the renal tubular responses to HTN (lean M and F
ZSF1) and T2D+HTN (obese M and F ZSF1 rats with early DKD). (2.1) A well-vetted and highly
translational rat model of diabetic kidney disease will be used to investigate the sexual dimorphisms
in progression of DKD including Na+ transporter regulation, fluid and electrolyte handling, renal injury
markers, and metabolic biomarkers. Completion of aim will provide much-needed picture of the
tubular responses to DKD progression in both sexes.
The goal of the proposed research is to define key renal compensatory mechanisms in females to
acute hypertension and the impact of diabetes with HTN in males and females. Overall, we aim to
apply what we learn about the female advantage to males and post-menopausal females to inform
treatments to reduce incidence and slow disease progression.

## Key facts

- **NIH application ID:** 10069080
- **Project number:** 1F31DK126457-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Brandon Eugene McFarlin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-05-12 → 2022-05-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069080

## Citation

> US National Institutes of Health, RePORTER application 10069080, Pressure Natriuresis and Renal Na+ Transporter Regulation in Males and Females: Impact of Diabetes with Hypertension (1F31DK126457-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10069080. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*