Effects Of Pannax Notoginseng Saponins On The Blood Pressure In The Anesthetized Mice, And Isolated Arteries And Atrium Of The Animals

Pannax notoginseng saponins (PNS) are the mainly active components of Panax notoginseng. Currently, PNS has been widely used in the treatment of coronary heart disease, and it has become a safe and effective medicine. However, pharmacological effects of PNS on the cardiovascular system are not so clear. Moreover, limited observations of the pharmacological effects of PNS on the cardiovascular system indicate that the purity of PNS may have a great influence on the evaluation of pharmacological and toxicological profiles of PNS.Objective: To observe the diastolic effects of PNS on the isolated coronary, aortic, mesenteric and tail arterial preparations, and the relationship between diastolic response induced by PNS and vascular endothelium. We also observe the effects of PNS on the isolated mouse atrium, and on the blood pressure in the anesthetized mice.Methods and results:1 Changes of vasoconstrictive responses to phenylephrine and KCl in the isolated arteries with or without endotheliumIn the isolated rabbit thoracic aorta, rat mesenteric artery and rat tail artery, phenylephrine (0.01¹00μmol·L^-1) produced concentration-dependent vasoconstriction in the preparation with or without endothelium. The results of two way ANOVA analysis indicated that the vasoconstrictive responses induced by phenylephrine in the rabbit thoracic aorta and rat mesenteric artery without endothelium were significantly stronger than those in the rabbit thoracic aorta and rat mesenteric artery with endothelium (P<0.01), however, we did not observe an obvious difference in the vasoconstrictive responses between endothelium-intact and endothelium-denuded tail arteries of the rat (P>0.05).KC1 (1⁷0mmol·L^-1) produced a concentration-dependent vasoconstriction in the isolated rabbit coronary artery whether with or without functional endothelium. The results of two way ANOVA analysis indicated that the vasoconstrictive response induced by KC1 in the coronary artery without endothelium was significantly bigger than that in the endothelium-intact coronary artery (P<0.05); however there was no significant difference between the individual datum (vasoconstrictive response) in the endothelium-intact artery and its respective control value in the endothelium-denuded artery (P>0.05).2 Vasodilative responses to PNS in the arterial preparations with or without endotheliumIn the isolated rabbit thoracic aorta, rat mesenteric artery and rat tail artery whether with or without functional endothelium, phenylephrine at EC50 produced a consistent and stable level of vasoconstriction for 90 min at least (P>0.05). PNS (1⁸0 mg·L^-1) induced vasodilative responses in a concentration-dependent manner in the three arteries precontracted with phenylephrine, and there was no difference between endothelium-intact and endothelium-denuded preparations (P>0.05). The maximal vasodilative responses to PNS at 80mg·L^-1 were 21.08±12.72% (endothelium-intact thoracic aorta), 17.32±2.72% (endothelium-denuded thoracic aorta), 30.91±18.78% (endothelium-intact mesenteric artery), 31.30±9.80% (endothelium-denuded mesenteric artery), 32.45±5.85% (endothelium-intact tail artery) and 34.88±15.71% (endothelium-denuded tail artery).In the isolated rabbit coronary arteries with or without functional endothelium, KCl at EC50 produced a consistent and stable level of vasoconstriction for 90 min at least (P>0.05). PNS (1⁸0 mg·L^-1) induced vasodilative responses in a concentration-dependent manner in the artery precontracted with KCl, and the vasodilative response to PNS in the endothelium-intact artery was much bigger than that in the endothelium-denuded preparation (P<0.05). The maximal vasodilative responses to PNS at 80mg·L^-1 were 86.25±11.59% (endothelium-intact coronary artery) and 66.96±16.95% (endothelium-denuded coronary artery).3 Vasodilative responses to PNS, RPTH and a combination of PNS and RPTH in the isolated rat thoracic aorta with endotheliumIn the endothelium-intact thoracic aorta of the rat, KCl at EC50 produced a consistent and stable level of vasoconstriction for 90 min at least (P>0.05). PNS, RPTF and PNS/RPTF (1⁸0 mg·L^-1) induced vasodilative responses in a concentration-dependent manner in the artery precontracted with KCl, and there was no significant difference in the vasodilative responses among the three agents (P>0.05). At a concentration of 80 mg·L^-1, PNS, RPTF and PNS/RPTF produced the maximal vasodilative responses by 23.50±15.50%, 19.17±16.75% and 13.16±14.0%, respectively.4 Effect of PNS on the blood pressure in the anesthetized miceIntravenous administration of PNS (1¹0 mg·kg^-1) produced an initial decrease and subsequent increase in the blood pressure in the anesthetized mice, and the changes in blood pressure were returned to the basic level within 20³0 min after administration. The results of two way ANOVA analysis indicated that in comparison with solvent, PNS produced a significant biphasic effect on the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP). The maximal changes in SBP, DBP and MABP induced by PNS at 10 mg·kg^-1 were -14.09±7.27% and 14.99±10.98%, -17.26±8.63% and 20.78±14.04%, and -16.04±8.06 % and 18.41±12.39%, respectively.5 Effects of PNS on the heart rate in the mouse isolated right atriumBefore administration of solvent and PNS, the heart rate in the mouse isolated right atrium of the both groups was not significantly different from each other (P>0.05). Solvent did not affect the heart rate significantly in the mouse isolated right atrium (P>0.05), and PNS (40, 80 and 160 mg·L^-1) also had no significant effect on the heart rate of the isolated mouse right atrium (P>0.05).6 Effects of PNS on the contractile force in the mouse isolated left atrium Before administration of solvent and PNS, the contractile force in the mouse isolated left atrium of the both groups was not significantly different from each other (P>0.05). Solvent did not affect the contractile force significantly in the mouse isolated left atrium (P>0.05), and PNS (40, 80 and 160 mg·L^-1) also had no significant effect on the contractile force of the isolated mouse left atrium (P>0.05).Conclusion:PNS at concentrations of 1⁸0 mg·L^-1 produces vasodilative responses in the rabbit thoracic aorta, rabbit coronary artery, rat mesenteric artery and tail artery, and its vasodilative response is much more potent in the rabbit coronary artery than that in the other 3 arteries. The vasodilative response to PNS is partially dependent on the function of endothelium of the rabbit coronary artery. Intravenous administration of PNS (1¹0 mg·kg^-1) produced an initial decrease and subsequent increase in the blood pressure slightly but obviously in the anesthetized mice. PNS at concentrations of 40¹60 mg·L^-1 does not affect the heart rate and contractile force in the mouse atrium. These results indicate that the biphasic effect on the blood pressure by PNS is not related to its direct heart effects.