Inhibitory effects of Caveolin-1-mediated atorvastatin on vasoconstriction of interlobar renal artery in SHR rats

Objective Excessive vasoconstriction of interlobar renal artery (IRA) is one of preliminary manifestations of renal damage in hypertension, during which caveolin-1 plays an important role. Atorvastatin (ATVS) represses cholesterol (CHO) synthesis to down-regulate the expression of caveolin-1, so we aimed to investigate whether the ATVS inhibited vasoconstriction of IRA to angiotensin Ⅱ (Ang Ⅱ) by regulating caveolin-1 in spontaneously hypertensive rats (SHR).Methods Twelve SHR were randomly divided into two groups:SHR control group, and SHR ATVS-treated group. Six Wistar Kyoto (WKY) rats weighing the same were employed as control group. Systolic blood pressure (SBP) was measured with the tail-cuff technique before and 2 or 4 weeks after ATVS treatment. Isometric force recording system was used to detect the vascular function. Western blotting was conducted to examine the protein abundance of caveolin-1 or angiotensin Ⅱ type 1 receptor (AT₁). Immumoprecipitation was carried out to assess the binding of caveolin-1 and AT₁.Results SBP, and intensity and sensitivity of vasoconstriction of IRA to Ang Ⅱ were significantly increased in SHR as compared to WKY rats (P<0.05). At 4th week, ATVS treatment could significantly reduce SPB(P<0.05), and the intensity and sensitivity of vasoconstriction of IRA to Ang Ⅱ (P<0.05) in SHR control group. Meanwhile, the protein expression of caveolin-1 or AT₁ as well as Ang Ⅱ elicited binding of caveolin-1 or AT₁ in IRA was higher in SHR than in WKY rats, which could also be reduced by ATVS (P<0.05). The ex vivo incubation of CHO raised the caveolin-1 protein content and promoted the binding of caveolin-1 and AT₁ in IRA of ATVS-treated SHR (P<0.05). At the same time, CHO enhanced the intensity and sensitivity of vasoconstriction of IRA to Ang Ⅱ (P<0.05).Conclusions ATVS mitigated the vasoconstriction of IRA to Ang Ⅱ in SHR, which was mediated by reducing caveolin-1 expression and inhibiting the binding of caveolin-1 and AT₁.