Ginsenoside Rb(1) 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 Rb(1) (Rb(1)) 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 Rb(1) 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 Rb(1) 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. Rb(1) 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 Rb(1)-associated reduction in the agonist-induced vasoconstriction in the rings treated with L-NAME + HG50. The effect of Rb(1) in the aortic rings treated with L-NAME + HG50 resulted from a decrease in extracellular Ca(2+) influx through the receptor-operated Ca(2+) channel (ROCC, 10(−6)–10(−4) M CaCl(2), p < 0.001; 10(−3)–2.5 × 10(−3) M CaCl(2), p = 0.001) and the voltage-gated Ca(2+) channel (VGCC, 10(−6) M CaCl(2), p = 0.003; 10(−5)–10(−2) M CaCl(2), p < 0.001), whereas Rb(1) did not interfere with Ca(2+) release from the sarcoplasmic reticulum. In conclusion, we found that Rb(1) 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 Rb(1) could be developed as a therapeutic target for ED in diabetes.