Upregulation of caveolin-1 contributes to aggravated high-salt diet-induced endothelial dysfunction and hypertension in type 1 diabetic rats

Abstract

AimsEndothelial dysfunction and hypertension is more common in individuals with diabetes than in the general population. This study was aimed to investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetic rats fed with high-salt diet. Main methodsType 1 diabetes (DM) was induced by intraperitoneal injection of streptozotocin (70mg·kg−1). Normal or diabetic rats were randomly fed high-salt food (HS, 8% NaCl) or standard food (CON) for 6weeks. Key findingsBoth HS (143±10mmHg) and DM+HS (169±11mmHg) groups displayed significantly higher systolic blood pressure than those in the CON group (112±12mmHg, P<0.01). DM+HS rats exhibited more pronounced impairment of vasorelaxation to acetylcholine and insulin compared with either DM or HS. Akt/endothelial nitric oxide synthase (eNOS) phosphorylation levels and nitric oxide (NO) concentration in DM+HS were significantly lower than in DM. The levels of caveolin-1 (cav-1) in DM+HS were significantly higher than that in DM and HS. Co-immunoprecipitation results showed increased interaction between cav-1 and eNOS in the DM+HS group. In the presence of cav-1 small interfering RNA (siRNA), eNOS phosphorylations in human umbilical vein endothelial cells (HUVEC) were significantly increased compared with control siRNA. Cav-1 was slightly but not significantly lower in HUVEC cultured with high glucose and high-salt buffer solution and pretreated with wortmannin or l-nitro-arginine methyl ester. SignificanceImpaired endothelial Akt activation and increased cav-1 expression and resultant decreased eNOS activation contributes to aggravated high-salt diet-induced endothelial dysfunction and hypertension in DM rats.