Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic rings.
1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.
Zhang
Chuan
C
Department of Natural Medicinal Chemistry, School of Pharmacy, Second Military Medical University, China.
Wang
Xu-Hui
XH
Zhong
Mei-Fang
MF
Liu
Run-Hui
RH
Li
Hui-Liang
HL
Zhang
Wei-Dong
WD
Chen
Hong
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D011810:Quinoxalines; D012503:Saponins; D014315:Triterpenes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; C052064:astragaloside A; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D002122:Calcium Chloride; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin