Abstract
Excessive sodium intake is known to increase the risk for hypertension, heart disease, and stroke. Individuals who are more susceptible to the effects of high salt are at higher risk for cardiovascular diseases even independent of their blood pressure status. Local activation of the renin-angiotensin system (RAS) in the brain, among other mechanisms, has been hypothesized to play a key role in contributing to salt balance. We have previously shown that deletion of the alternative renin isoform termed renin-b disinhibits the classical renin-a encoding preprorenin in the brain resulting in elevated brain RAS activity. Thus, we hypothesized that renin-b deficiency results in higher susceptibility to salt-induced elevation in blood pressure. Telemetry implanted Ren-bNull and wildtype littermate mice were first offered a low salt diet for a week and subsequently a high salt diet for another week. A high salt diet induced a mild blood pressure elevation in both Ren-bNull and wildtype mice, but mice lacking renin-b did not exhibit an exaggerated pressor response. When renin-b deficient mice were exposed to a high salt diet for a longer duration (4 weeks), there was a trend for increased myocardial enlargement in Ren-bNull mice when compared with control mice, but this did not reach statistical significance. Multiple studies have also demonstrated the association of environmental stress with hypertension. Activation of the RAS in the rostral ventrolateral medulla and the hypothalamus is required for stress-induced hypertension. Thus, we next questioned whether the lack of renin-b would result in exacerbated response to an acute restraint-stress. Wildtype and Ren-bNull mice equally exhibited elevated blood pressure in response to restraint-stress, which was similar in mice fed either a low or high salt diet. These studies suggest that mechanisms unrelated to salt and acute stress alter the cardiovascular phenotype in mice lacking renin-b.
Highlights
High blood pressure is a leading cause of complications from heart disease, stroke, and kidney disease
Retrospective analysis of blood pressure in five cohorts of Ren-bNull and WT mice indicated that mice lacking Ren-b exhibit a high degree of variability in blood pressure
The range of blood pressure in control mice was much smaller (5.5 mmHg). We hypothesized that these differences might be attributed to environmental factors as a review of conditions under which the cohorts were studied revealed that cohorts 1, 2, 3, and 4 were housed in a large room with an elevated level of noise and traffic, while mice in cohort 5 were housed in a smaller and newer quiet animal facility located in a different building
Summary
High blood pressure is a leading cause of complications from heart disease, stroke, and kidney disease. It has been shown that in both normotensive and hypertensive subjects, increased sensitivity to sodium increases the risk for cardiovascular mortality and morbidity [1]. The increased prevalence of hypertension in the last century has been attributed in part to the higher consumption of dietary salt [2]. Salt and stress in renin-b deficient mice. JLG (HL134850), PN (HL153101) and grants from the American Heart Association to CDS (15SFRN23480000), JLGrobe (18EIA33890055). PN was funded with training awards from the NIH for this study (2T32HL007121041, 4T32DK007690, and 5T32HL134643)
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