| Objective: In recent years,as a dietary intervention for metabolic diseases such as obesity and diabetes,whether ketogenic diet is suitable for patients with hypertension is unknown.This study aims to investigate the effects of ketogenic diet on hypertension,metabolism and renal fibrosis in spontaneously hypertensive rats,and to provide an animal basis for patients with hypertension to benefit from ketogenic diet.Methods: Male spontaneously hypertensive(SHR)and Wistar Kyoto(WT)rats were randomly divided into a ketogenic diet group(n = 8)and a normal diet group(n = 4).Ketogenic diet was composed of 10% protein and 90% fat.Body weight,blood glucose and blood lipid were measured after 4 weeks;Then,blood pressure and vascular function were evaluated,expression of eNOS in mesenteric artery was detected,and the potential mechanism of ketone body(β-hydroxybutyric acid)on the expression of eNOS in human umbilical vein endothelial cells was investigated.Next,renal autophagy-related protein expression was detected with western blot,and renal fibrosis was detected by Masson staining.Results: compared with normal diet,the ketogenic diet led to significantly decreased glucose and body weight in SHR and WT;increased triglyceride and β-hydroxybutyric acid levels,overactivated the rennin-angiotension-aldosterone system to aggravate hypertension and impaire the endothelium-dependent relaxation function of mesenteric artery in SHR,and inhibits the expression of eNOS and CD31 in mesenteric artery,study in vitro showed that ketone body and TGF-β can significantly reduce the expression of eNOS and CD31 in human umbilical vein endothelial cells,and increase the expression of α-SMA.In addition,the KD can reduced renal autophagy-related protein expression of LC3 and ULK in SHRs,Masson staining and other experiments showed that the KD had no significant effect on hypertensive renal fibrosis.Conclusion: KD could reduce the weight and blood glucose,aggravate the disorder of lipid metabolism,increase hypertension by activating the RAAS and impaire endothelium-dependent relaxation of mesenteric artery,and aggravate the development of hypertension in SHR;meanwhile,reduce the expression level of autophagy related proteins in kidney.Therefore,though ketogenic diet can reduce body weight and blood glucose,it has adverse effects on vascular function,vascular remodeling and target organs in SHR.It is necessary to be cautious in clinical treatment of metabolic diseases with hypertension. |
