The effect of time-restricted feeding on kidney pathology in salt sensitive hypertension

Abstract

Salt-sensitivity (SS) continues to be a large contributor to hypertension and increases the risk of developing chronic kidney disease. Treatment options remain limited to consumption of a low-sodium diet and administration of different pharmaceuticals and yet some individuals remain hypertensive. The goal of this study was to examine whether time-restricted feeding (TRF) can lessen renal damage secondary to SS hypertension. TRF has been previously shown to improve inflammation, dyslipidemia, and hypertension in cardiometabolic disorders, however it has not been well studied in SS. When fed a high salt (HS) diet, the Dahl SS rat, a well-known animal model of SS hypertension, experiences enhanced Na+ reabsorption and increased blood pressure followed by exacerbated renal pathology, mimicking what is seen clinically. Increased Na+ reabsorption requires high amounts of ATP, which is normally produced via fatty acid beta oxidation (FAO). Published and preliminary studies have revealed that SS rats experience a decrease in renal FAO and associated lipotoxicity. We hypothesized that TRF would improve renal FAO and slow the progression of renal injury seen in SS hypertension. Male SS rats (10-wk-old) were divided into either the HS ad libitum or the HS TRF group (n=8/group) and underwent a two-week protocol. During week one, all rats had ad libitum access to the HS diet to develop hypertension. During week two, TRF was implemented by providing food for 8 hours during the active cycle. Prior to endpoint, but immediately after the feeding period, anesthetized blood pressure was measured via carotid artery catheterization. HS TRF rats experienced a significant increase in systolic and diastolic blood pressure compared to the HS ad libitum group (SBP 175.56 ± 11.43 mmHg vs 141.27 ± 8.68 mmHg; DBP 118.92 ± 7.37 mmHg vs 95.14 ± 6.01 mmHg; mean ± SEM; p < 0.05, t-test). Despite an increase in blood pressure, analysis of renal fibrosis revealed that HS TRF rats had a significant decrease in cortical and outer medullary (OM) fibrosis compared to the ad libitum fed groups (cortical: 2.58 ± 0.068% vs 5.21± 0.44%; OM: 3.09 ± 0.31% vs 6.04 ± 0.81%; mean ± SEM; p < 0.05, t-test). Assessment of renal lipid accumulation revealed that HS TRF rats appear to have reduced lipid droplets compared to the HS ad libitum rats. Further, HS TRF rats had decreased body weight adjusted ventricle weight compared to the HS ad libitum group (0.31 ± 0.0058% vs 0.35 ± 0.012%; mean ± SEM; p < 0.05, t-test). Together these data suggest the elevated blood pressure measured in the HS TRF group may be transient, resulting from the salt load following the feeding period. This study revealed that TRF may have the potential to reduce renal pathology seen in SS hypertension. Future studies will address how blood pressure changes with timing of the salt load and how TRF impacts renal FAO. Support provided by NIH Grant T32HL007852 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.