Renal Tubule Cell-Specific Npr1 is Essential to Regulate Blood Pressure and Kidney Dysfunction

Authors

• Kandasamy Neelamegam, Tulane University Health Sciences Center, New Orleans, LA
• Chandramohan Ramasamy, Tulane University Health Sciences Center, New Orleans, LA
• Ramachandran Samivel, Tulane University Health Sciences Center, New Orleans, LA
• Shoujin Hao, New York Medical College, Valhalla, NY
• Nicholas R. Ferreri, New York Medical College, Valhalla, NY
• Zheng Dong, Charlie Norwood VA Medical Center, Augusta, GA
• Huijing Xia, LSU Health Sciences Center - New OrleansFollow
• Daniel R. Kapusta, LSU Health Sciences Center - New OrleansFollow
• Kailash N. Pandey, Tulane University Health Sciences Center, New Orleans, LA

Document Type

Article

Publication Date

4-30-2026

Publication Title

Hypertension

Abstract

BACKGROUND: Atrial and brain natriuretic peptides activate GC-A/NPRA (guanylyl cyclase-A/natriuretic peptide receptor-A) and regulate blood pressure and electrolyte homeostasis. Renal tubule (RT) dysfunction results in decreased kidney function and increased blood pressure. We determined the sex-specific consequences of RT cell-specific deletion of Npr1 (encoding NPRA) on blood pressure and renal hemodynamics. METHODS: Mice were generated with inducible RT knockout by breeding lox-flanked (flox/flox: f/f) exons 1 to 2 in Npr1 with mice expressing the Pax8-rtTA-LC-1-Cre transgene. Doxycycline-treated RT cell-specific Npr1 knockout (Npr1 f/-), heterozygous (HT; Npr1 f/+), and wild-type (Npr1 f/f) male and female mice were used. Proximal tubule, distal tubule, and cortical collecting duct were isolated from RT-Npr1 knockout mice and did not express Npr1 mRNA or protein. RESULTS: RT cell-specific male knockout and HT mice showed significantly lower glomerular filtration rate, creatinine clearance, and urinary sodium excretion than female mice, compared with wild-type mice. The effect of Npr1 deletion was more severe on high-salt diets than their normal-diet counterparts. Loss of Npr1 in RT segments significantly increased systolic blood pressure and mean arterial pressure in a sex-specific manner. Mutant male mice showed higher total urinary protein and albumin-creatinine ratios than female mice. On a high-salt diet, male knockout and HT mice showed greater salt sensitivity than female mice. CONCLUSIONS: Loss of Npr1 along the nephron tubules leads to arterial hypertension and abnormal renal functional hemodynamic changes that are more pronounced in male mice compared with female mice.

First Page

e25890

PubMed ID

42059085

Volume

83

Issue

7

Rights

© 2026 American Heart Association, Inc.

Recommended Citation

Neelamegam, Kandasamy; Ramasamy, Chandramohan; Samivel, Ramachandran; Hao, Shoujin; Ferreri, Nicholas R.; Dong, Zheng; Xia, Huijing; Kapusta, Daniel R.; and Pandey, Kailash N., "Renal Tubule Cell-Specific Npr1 is Essential to Regulate Blood Pressure and Kidney Dysfunction" (2026). School of Graduate Studies Faculty Publications. 596.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/596
10.1161/HYPERTENSIONAHA.125.25890