INFLUENCE OF CHRONIC AT1 RECEPTOR BLOCKADE ON GASTRIC BARRIER FUNCTION IN MICE

Abstract

Objective: The AT1 receptor blocker Telmisartan (TEL) is beneficial for the treatment of individuals suffering the Metabolic Syndrome as TEL reveals not only antihypertensive effects but also improves the glucose and lipid control and lowers body weight. As we have recently shown that TEL has impact on gut microbiota and brain barrier function we here investigated whether TEL influences gut barrier function which may participate in decrease of energy intake. Design and method: BL6 mice were fed with chow or high fat diet (45% fat) and were additionally treated with vehicle (CONchow or CONHFD) or TEL (8 mg/kg/d, 12 w, TELchow or TELHFD). Visceral and subcutaneous fat mass was quantified by MRI. Segments of large intestine were Canoy fixed to determine thickness of mucus by immunohistochemistry. PAS staining was performed for depicting goblet cells. The signalling pathway being involved in necroptosis was investigated by Western blots and qPCR. Results: Compared to chow feeding, gain in body weight increased by HFD (3.4±0.5 vs. 14.4g±1.2 g) and was reduced by TEL (1.7±0.5 vs. 2.8±0.5g). Visceral fat and liver mass was higher in CONHFD than CONchow but remained normal by TEL treatment. The mucus thickness was lower in CONHFD than CONchow. Independent on feeding, TEL additionally reduced mucus thickness. Numbers of goblet cells were not affected by HFD feeding and TEL treatment. RIP3 was particularly increased in TELHFD mice, while muc2 and ki67 almost remained unaffected by TEL. Conclusions: In contrast to our expectation, the antiobese effect of TEL was associated with a decrease in mucus thickness. Increase in RIP3 indicates that necroptosis may be enhanced by TEL. Further studies have to be performed to elucidate whether this detrimental TEL effect is true and be relevant for gastrointestinal function.