MPS 13-02 DIETARY FIBRE INTAKE PREVENTS HYPERTENSION AND IMPROVES RENAL FUNCTION IN A MINERALOCORTICOID-EXCESS MODEL. (September 2016)

• Record Type: Journal Article
• Authors: Marques, Francine; Nelson, Erin; Chu, Po-Yin; Horlock, Duncan; Fiedler, April; Kuruppu, Sanjaya; Rajapakse, Niwanthi; Mackay, Charles; Kaye, David
• Is Part Of: Journal of hypertension. Volume 34:(2016) Supplement 1
• Publication Date: 2016-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000501048.23225.c6
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Although dietary intake of fruit and vegetables is associated with lower incidence of hypertension, the mechanism involved is not clear. Consumption of a diet high in fibre increases gut microbiota populations that generate short chain fatty acids (SCFAs) such as acetate, which has a protective role in experimental models of inflammatory diseases. Here we established the effect of a high fibre diet and acetate on the development of hypertension and renal function in a mineralocorticoid-excess (MRE) model. Design and Method: Mice were fed control chow (5% fibre), high fibre chow (35% fibre) or water supplemented with acetate for 3 weeks, and then submitted to sham (uninephrectomy) or MRE (uninephrectomy + DOCA tablet) surgeries (n = 11–14/group). At the end of 6 weeks, renal structure and function, blood pressure and gene expression were examined. Results: Compared to MRE mice fed a normal diet, high fibre diet significantly reduced systolic (control DOCA vs high fibre DOCA mean ± SEM: 116 ± 19 mmHg vs 91 ± 5 mmHg, P = 0.0009) and diastolic blood pressure (75 ± 5 mmHg vs 58 ± 5 mmHg, P = 0.0004), glomerular filtration rate (724.8 ± 122 μl/min vs 139.8 ± 23 μl/min, P = 0.023) and urine volume (10.02 ± 3 μl/min vs 2.15 ± 0.8 μl/min, P = 0.032), while there was no change in renal fibrosis. Acetate had a similar effect on blood pressure and renal function, whilst also reduced glomerular and tubulointerstitial fibrosis (all P < 0.05). The protective effects of high fibre and acetate were accompanied by a reduction in immune activation (Cd8a, Ctla4, Il6, Mcp1 and Tlr1 mRNA) together with a decrease in the levels of histone deacetylase 3 (Hdac3) (all P < 0.05), an important epigenetic regulator of immune cell function which also targets the mineralocorticoid receptor. Conclusions: Our data supports that dietary high fibre intake could decrease blood pressure and improve renal function during MRE. The mechanism may involve the SCFA acetate, which had an immunomodulatory role through Hdac3.