Abstract P394: Reduced Serum Butyrate Is Associated With Dampened Central Effects Of Butyrate On Blood Pressure In The Shr

Abstract

Introduction: The link between gut dysbiosis and hypertension is characterized by a significant reduction in butyrate-producing bacteria in the spontaneously hypertensive rat (SHR) compared with its Wistar Kyoto (WKY) control. Butyrate, a major end-product of gut microbiota fermentation, has beneficial effects in multiple dysbiosis-related diseases. Here, we investigated the link between serum butyrate levels and central effects of butyrate in regulation of blood pressure (BP) in WKY and SHR. Methods: Serum samples were collected from 12 weeks old male WKY and SHR, and butyrate quantification was performed using LC-MS. Quantitative real time PCR was employed to measure relative expression levels of butyrate sensing receptors (Gpr41, Gpr43) in the hypothalamus of SHR and WKY. Central effects of butyrate on BP were evaluated by acute ICV injection in anaesthetized WKY and SHR. Results: Significantly lower levels of serum butyrate were observed in the SHR (WKY 1.23±0.14μmol/L vs SHR 0.23±0.033μmol/L, N=4, P=0.0005). Moreover, lower expression of Gpr43 were observed in the hypothalamus of SHR (WKY 0.0002 ± 2.7e-005 vs SHR 6.9e-005 ± 1.9e-005, N=4/3, P=0.0152). ICV administration of butyrate reduced BP in both strains; however, the reduction in arterial BP was greater in the WKY at two time points (400s post-injection: WKY -5.83±0.49mmHg vs SHR -2.62±0.63mmHg, N=4, P=0.0235; 1000s post-injection: WKY -19.7±1.85mmHg vs SHR -13.26±1.1mmHg, N=3, P=0.05). Conclusion: Reduced serum butyrate is associated with reduced sensitivity to central butyrate. This may contribute to elevation in BP in the SHR.