Endothelium-dependent vasodilation effects of Panax notoginseng and its main components are mediated by nitric oxide and cyclooxygenase pathways

Abstract

Panax notoginseng, a traditional Chinese herbal medicine, has been used for the treatment of cardiovascular diseases. The main bioactive components of this species are Panax notoginseng saponins (PNS). The present study aimed to investigate the effects of PNS and five of its main components (ginsenosides Rg1, Re, Rb1 and Rd, and notoginsenoside R1) on rat aorta rings pre-contracted with norepinephrine (NE) and to determine the underlying mechanism of action. Isolated aorta rings (with or without intact endothelium) from adult male Wistar rats were stimulated with NE to induce vasoconstriction, and subsequently treated with different concentrations of PNS and its five main components (Rg1, Re, Rb1, R1 and Rd) separately. This procedure was repeated after pre-incubation with the nitric oxide (NO) synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME), the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cyclooxygenase (COX) inhibitor indomethacin (INDO), in order to elucidate the mechanism of action of PNS and its components. The results demonstrated that PNS and the components Rg1, Re, Rb1 and R1, but not Rd, induced vessel relaxation in a concentration-dependent manner when the endothelium lining was intact. NO synthase inhibitor L-NAME and guanylate cyclase inhibitor ODQ attenuated the diastolic effects of PNS, Rg1, Re, Rb1 and R1 in aortic rings with intact endothelium. By contrast, INDO, a known COX inhibitor weakened the vasodilation effects of PNS, Re and Rb1 but demonstrated no effect on Rg1 and R1. In conclusion, PNS and two of its main components (Re and Rb1) exert vasodilating effects through the NO and COX pathways.

Keywords: Panax notoginseng saponins; aortic ring; cyclooxygenase; ginsenoside Rb1; ginsenoside Rd; ginsenoside Re; ginsenoside Rg1; nitric oxide; notoginsenoside R1.

Figure 1.

Norepinephrine-induced vasoconstriction of aortic rings with or without endothelium. After being progressively stretched to a basal tension of 2.0 g and equilibrated for ≥90 min, different concentrations of (A) Panax notoginseng saponins, (B) ginsenoside Rg1, (C) ginsenoside Re, (D) ginsenoside Rb1, (E) notoginsenoside R1 and (F) ginsenoside Rd were added cumulatively. **P<0.01 vs. time 0.

Figure 2.

Vasoconstriction of rat aortic rings in the presence and absence of L-NAME. Inhibition of norepinephrine-pre-contracted rat thoracic aorta rings with intact endothelium in response to the cumulative addition of (A) PNS, (B) Rg1, (C) Re, (D) Rb1 and (E) R1 in the presence and absence of L-NAME. PNS, Panax notoginsenoside saponins; L-NAME, N^G-nitro-L-arginine methyl ester. *P<0.05, **P<0.01 vs. the group with endothelium.

Figure 3.

Vasoconstriction of rat aortic rings in the presence and absence of ODQ. Inhibition of norepinephrine-pre-contracted rat thoracic aorta rings with intact endothelium in response to cumulative addition of (A) PNS, (B) Rg1, (C) Re, (D) Rb1 and (E) R1 in the presence and absence of ODQ. PNS, Panax notoginsenoside saponins; ODQ, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one.**P<0.01 vs, the group with endothelium.

Figure 4.

Vasoconstriction of rat aortic rings in the presence and absence of INDO. Inhibition of norepinephrine-pre-contracted rat thoracic aorta rings with intact endothelium in response to cumulative addition of (A) PNS, (B) Rg1, (C) Re, (D) Rb1 and (E) R1 in the presence and absence of INDO. PNS, Panax notoginsenoside saponins; INDO, indomethacin. *P<0.05, **P<0.01 vs. the group with endothelium.