Astragaloside IV dilates aortic vessels from normal and spontaneously hypertensive rats through endothelium-dependent and endothelium-independent ways.
The major active constituent of Astragalus membranaceus, astragaloside IV, has been found to have properties of increasing coronary flow and cardioprotection. In this study, we examined the direct effects of astragaloside IV on vessel dilatation and contraction in isolated aortic rings from both normal and stroke-prone spontaneously hypertensive rats (SHR-SP) in vitro. The results demonstrated that astragaloside IV could antagonize vessel contractions induced by phenylephrine and potassium chloride in a concentration-dependent way. Astragaloside IV reduced CaCl2-induced contractions in Ca2+-free solution. Astragaloside IV also dilated aortic vessels in a dose-dependent manner, which was partially endothelium-dependent through the nitric oxide (NO) and cGMP pathways. The aorta from 6-month-old SHR-SP rats showed impaired endothelium function, and astragaloside IV dilated the vessels from the hypertensive rats to a lesser extent as compared with normal control rats. In the presence of perivascular fat tissue, the contractile responses induced by angiotensin II and phenylephrine were also attenuated by astragaloside IV. Collectively, this study provides functional evidence that astragaloside IV exerts vessel dilatation properties through the endothelium-dependent NO-cGMP pathway in normal and hypertensive rats. It blocks extracellular calcium influx and participates in vessel relaxation partly through phenylephrine and angiotensin II inhibition when perivascular fat is present.
Zhang
Wei-Dong
WD
Department of Natural Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, P. R. China. WDZhangY@hotmail.com
Zhang
Chuan
C
Wang
Xu-Hui
XH
Gao
Ping-Jin
PJ
Zhu
Ding-Liang
DL
Chen
Hong
H
Liu
Run-Hui
RH
Li
Hui-Liang
HL
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000187:drug effects*
D002316:Cardiotonic Agents; D012503:Saponins; D014315:Triterpenes; D014662:Vasoconstrictor Agents; C052064:astragaloside A