All ETDs from UAB

Advisory Committee Chair

Jennifer S Pollock

Advisory Committee Members

David M Pollock

Edward W Inscho

Document Type

Thesis

Date of Award

2018

Degree Name by School

Master of Science in Multidisciplinary Biomedical Science (MSBMS)

Abstract

We previously reported that nitric oxide synthase-1 (NOS1) in the collecting duct (CD) is critical for maintaining fluid-electrolyte balance during high salt diet. Lack of NOS1 in the CD (CDNOS1KO) results in reduced sodium excretion, urine output, and urinary nitrite/nitrate excretion compared to male control mice after 1 day of a high salt diet (4% NaCl). By day 7 of a high salt diet, CDNOS1KO mice display significantly increased systolic blood pressure with sodium excretion returning to levels similar to control mice. Sex differences in renal sodium handling are important to consider. Female rodents possess redundant mechanisms for sodium handling that provides protection against renal injury. This has been proposed to be due to tubular transport, rather than renal hemodynamics. The overall hypothesis of this study is that lack of CD NOS1 blunts the physiological renal hemodynamic response to a high salt diet in male and female mice. We designed experiments to test this hypothesis in two specific aims: Aim 1: To determine if female CDNOS1KO mice have attenuated sodium excretion and urine output response to a high salt diet similar to previously reported in male CDNOS1KO mice. Aim 2: To determine whether the glomerular filtration rate (GFR) in response to varying salt diets is similar in males and females of control and CDNOS1KO mice. Metabolic cages studies were used to determine 24-hour urine output and food consumption. Urine was stored, and analyzed for urine electrolytes and metabolites. GFR was measured by transdermal FITC-sinistrin clearance in conscious male and female control and CDNOS1KO mice on three different salt diet challenges. Our results indicate that CD NOS1 is critical for the hemodynamic adaptation to a high salt diet in both male and female mice. Sex differences may be present in the ability to excrete sodium, with female control mice being better acclimated to handle a salt load.

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