High sodium diet increases urinary endothelin-1 excretion in women but not in men.
Abstract
Introduction:
Gender differences in the prevalence of hypertension have been well established, and endothelin-1 (ET-1) is a proposed player in these differences. In the kidney, ET-1 serves as a pro- natriuretic peptide, and urinary ET-1 excretion reflects renal production of ET-1. Previous studies in our lab demonstrated that on a normal salt diet, female rats had higher urinary ET-1 excretion than male rats, and on a high salt diet, only male rats had an increase in urinary ET-1. However, the effect of dietary salt loading on the renal endothelin-1 system in humans is not clear; thus, we aim to investigate the effect of increasing dietary sodium intake on urinary ET-1 excretion in men and women. We hypothesized that women would have higher overall urinary ET-1 excretion than men, and increasing dietary sodium would augment urinary ET-1 excretion only in men.
Methods:
25 salt-resistant human participants with baseline blood pressure of less than 140/90 mmHg followed recommended sodium (RS) and high sodium (HS) diets (2300 and 7000 mg/day) for 10 days. The diets were administered in randomized order with a washout period of at least four weeks between each intervention. At the end of each dietary phase, 24-hour ambulatory blood pressure was measured, and 24-hour urine was collected. ET-1 excretion was quantified using the QuantiGlo (R&D) ET-1 ELISA assay and was normalized to urine flow.
Results:
Women had higher urinary ET-1 excretion than men, which was more pronounced on the HS diet, and only women had a significant increase in ET-1 excretion on the HS diet. Mean arterial pressure, systolic blood pressure, and diastolic blood pressure did not increase significantly with the HS diet in either men or women. HS diet increased urine flow in women but not in men, and there was no significant gender difference in urine flow.
Conclusion:
Women have higher overall urinary ET-1 excretion than men, particularly on a HS diet, and in opposition to our hypothesis, a HS diet increases urinary ET-1 excretion only in women. Further work is warranted to evaluate urinary ET-1 excretion in women and men on different sodium diets, especially considering the variance in sodium consumption across the United States. Understanding gender differences in ET-1-mediated sodium regulation in humans could potentially inform future studies towards developing gender-specific therapeutics for hypertension.