Ginsenoside Rb₁ Reduces Hyper-Vasoconstriction Induced by High Glucose and Endothelial Dysfunction in Rat Aorta

Acute hyperglycemia induces oxidative damage and inflammation, leading to vascular dysfunction. Ginsenoside Rb₁ (Rb₁) is a major component of red ginseng with anti-diabetic, anti-oxidant and anti-inflammatory properties. Here, we investigated the beneficial effects and the underlying mechanisms of Rb₁ on hypercontraction induced by high glucose (HG) and endothelial dysfunction (ED). The isometric tension of aortic rings was measured by myography. The rings were treated with N^G-nitro-L-arginine methyl ester (L-NAME) to induce chemical destruction of the endothelium, and Rb₁ was added after HG induction. The agonist-induced vasoconstriction was significantly higher in the aortic rings treated with L-NAME + HG50 than in those treated with HG50 or L-NAME (p = 0.011) alone. Rb₁ significantly reduced the hypercontraction in the aortic rings treated with L-NAME + HG50 (p = 0.004). The ATP-sensitive K⁺ channel (K_ATP) blocker glibenclamide tended to increase the Rb₁-associated reduction in the agonist-induced vasoconstriction in the rings treated with L-NAME + HG50. The effect of Rb₁ in the aortic rings treated with L-NAME + HG50 resulted from a decrease in extracellular Ca²⁺ influx through the receptor-operated Ca²⁺ channel (ROCC, 10^-6-10^-4 M CaCl₂, p < 0.001; 10^-3-2.5 × 10^-3 M CaCl₂, p = 0.001) and the voltage-gated Ca²⁺ channel (VGCC, 10^-6 M CaCl₂, p = 0.003; 10^-5-10^-2 M CaCl₂, p < 0.001), whereas Rb₁ did not interfere with Ca²⁺ release from the sarcoplasmic reticulum. In conclusion, we found that Rb₁ reduced hyper-vasoconstriction induced by HG and ED by inhibiting the ROCC and the VGCC, and possibly by activating the K_ATP in rat aorta. This study provides further evidence that Rb₁ could be developed as a therapeutic target for ED in diabetes.