The protective effects of ginsenoside Rg1 against hypertension target-organ damage in spontaneously hypertensive rats

Abstract

Background: Although a number of medicines are available for the management of hypertension, the organ damage induced by hypertension is not resolved. The aim of this study was to investigate the protection of ginsenoside Rg1 (Rg1) against vascular remodeling and organ damage in spontaneously hypertensive rats (SHR).

Methods: Male SHR were treated with 5, 10 or 20 mg/kg Rg1 through intraperitoneal injection per day for 1 month. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (saline) was used as control. Blood pressure detection and pathological stain, transmission electron microscope, immunohistochemical assay were used to elucidate the protection of Rg1.

Results: Blood pressures were not different between control SHR rats and Rg1 treated SHR rats, but Rg1 improved the aortic outward remodeling by lowering the lumen diameter and reducing the media thickness according the histopathological and ultrastructural detections. Rg1 also protected the retinal vessels against inward remodeling detected by immunohistochemical assay. Furthermore, Rg1 attenuated the target heart and kidney damage with improvement on cardiac and glomerular structure.

Conclusions: These results suggested that Rg1 held beneficial effects on vascular structure and further protected against the organ-damage induced by hypertension. These findings also paved a novel and promising approach to the treatment of hypertensive complications.

Figure 1

Chemical structure of Rg1.

Figure 2

Effects of Rg1 on aorta structure. (A) Representative sections of the aortas staining with hematoxylin-eosin (magnification 40X). (B) Representative sections of the aortas staining with hematoxylin-eosin (magnification 200X) (C) Representative sections of the aortas staining with Sirius red ((magnification 40X) (D) Representative sections of the aortas staining with Sirius red (magnification 200X) (E) Quantitative data of lumen diameter. (F) Quantitative data of media thickness. ###p < 0.001 compared with WKY, ***p < 0.001 compared with SHR. n = 4 for each group.

Figure 3

Effects of Rg1 on retinal remodeling induced by hypertension. Whole-mount double-staining of retinal vessels with FITC-coupled lectin (green) and α-SMA antibody (red). (A) lectin positive arteries. (B) α-SMA–positive arteries. (C) The merged picture for both (A) and (B). (D) Quantitative data of lumen diameter for retinal arteries. ###p < 0.001 compared with WKY; **p < 0.01, **p < 0.01 compared with SHR. n = 4 for each group.

Figure 4

Representative photographs of transmission electron microscopy for vascular smooth muscle cells. Arrows indicate mitochondria. n = 3 for each group. The representative figures were shown.

Figure 5

Rg1 improved heart and kidney structure of SHR detected by hematoxylin-eosin stain. (A) Representative photomicrographs from heart tissue of WKY, SHR, SHR-Rg1(5), SHR-Rg1(10), SHR-Rg1(20) with 200 X magnification. (B) Representative photomicrographs from kidney tissue of WKY, SHR, SHR-Rg1(5), SHR-Rg1(10), SHR-Rg1(20) with 200 X magnification. n = 4 for each group.

Figure 6

Rg1 decreased heart fibrosis induced by hypertension. (A) Representative perivascular area of whole heart stained by Sirius red. (B) Representative few-vascular area of whole heart stained by Sirius red. The position of collagen deposition was stained in red. n = 4 for each group.

Figure 7

Rg1 improved ultra-structure of heart and kidney. (A) Electron micrograph of mitochondria marked by arrow in heart. (B) Electron micrograph of glomerular basement membrane. n = 3 for each group. The representative figures were shown.