Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.

Hao Yu,Shiqiang Xiong,Tao Yang,Daoyan Liu,Hexuan Zhang,Peng Gao,Yu Zhao,William J Arendshorst,Zongshi Lu,Li Li,Qianhui Shang,Xing Wei,Jing Chen,Zhiming Zhu,Xiao Wei

doi:10.1038/srep25746

Abstract

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC.

Highlights

High salt intake is a major risk factor for hypertension
Despite lower water and food intake in the first three days, chronic caffeine intake had no effect on water and food intake in Dahl salt-sensitive (Dahl-S) rats thereafter (Fig. 1a,b), but significantly decreased their body weight compared with controls from the 12th day of treatment (Fig. 1c)
This anti-hypertensive effect of chronic caffeine was more obvious at night when the rats were more active (Fig. 1f). 24 hr ambulatory diastolic blood pressure did not differ between the two groups (Fig. 1g)

Summary

Introduction

High salt intake is a major risk factor for hypertension. acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. We investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. Acute effect of caffeine increases blood pressure and heart rate[10,11], chronic caffeine administration prevents diet-induced insulin resistance[12,13], attenuates metabolic syndrome through weight loss and reduction in fat mass[14] as well as reduces fructose-induced hypertension[15]. Caffeine can activate AMPK in different type of cells, including the vascular endothelial cells, skeletal muscle cells and hepatocytes[22,23,24] It is unknown whether caffeine regulates ENaC function in distal nephron through AMPK or other kinases

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Results

Conclusion