Abstract
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.
Key words
Astragaloside IV - vasodilatation - endothelium - perivascular fat - hypertension
References
-
1
Zhou J Y, Fan Y, Kong J L, Wu D Z, Hu Z B.
Effects of components isolated from Astragalus membranaceus Bunge on cardiac function injured by myocardial ischemia reperfusion in rats.
China J Chin Mater Med.
2000;
25
300-2
-
2
Liu Y X, Liu Z P, Jiao J J.
Influence of astragaloside IV on normal and depressed ventricular heart function in rats.
Zhong Cao Yao.
2001;
32
332-4
-
3
Zhou S, Shao W, Wang W.
Clinical study of Astragalus injection plus ligustrazine in protecting myocardial ischemia reperfusion injury.
Chin J Integr Trad Western Med.
2000;
20
504-7
-
4
Luo Y, Qin Z, Hong Z, Zhang X, Ding D, Fu J H. et al .
Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia.
Neurosci Lett.
2004;
363
218-23
-
5
Li Z P, Cao Q.
Effects of astragaloside IV on myocardial calcium transport and cardiac function in ischemic rats.
Acta Pharmacol Sin.
2002;
23
898-904
-
6 Zhang W D, Chen H, Zhang C, Li H L, Liu R H, Chen H Z. Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro
. Planta Med, in press
-
7
Wang H K, He K, Ye J L.
Chemical constituents of Astragalus mongholicus
.
Zhong Cao Yao.
1987;
18
5-7
-
8
Löhn M, Dubrovaska G, Lauterbach B, Luft F C, Gollasch M, Sharma A M.
Periadventitial fat releases a vascular relaxing factor.
FASEB J.
2002;
16
1057-63
-
9
Tirapelli C R, Ambrosio S R, da Costa F B, Coutinho S T, de Oliveira D CR, de Oliveira A M.
Analysis of the mechanisms underlying the vasorelaxant action of kaurenoic acid in the isolated rat aorta.
Eur J Pharmacol.
2004;
492
233-41
-
10
Hudgins A, Weiss G.
Effects of Ca2+ removal upon vascular smooth muscle contraction induced by norepinephrine, histamine and potassium.
J Pharmacol Exp Ther.
1968;
159
91-7
-
11
Hirata S, Enoki T, Kitamura R, Vinh V H, Nakamura K, Mori K.
Effects of isoflurane on receptor-operated Ca2+ channels in rat aortic smooth muscle.
Brit J Anaesth.
1998;
81
578-83
-
12
Lee C N, Wong K L, Liu J C, Chen Y J, Cheng J T, Chan P.
Inhibitory effect of stevioside on calcium influx to produce antihypertension.
Planta Med.
2001;
67
796-9
-
13
Gu Y, Deng D M.
Progress in hypertension with Qi-deficiency and blood stasis.
J Tradit Chin Med.
2001;
19
324-6
-
14
Robertson B E, Schubert R, Hescheler J, Nelson M T.
cGMP-dependent protein kinase activates Ca2+-activated K+ channels in cerebral artery smooth muscle cells.
Am J Physiol.
1993;
265
C299-303
-
15
Garthwaite J, Southam E, Boulton C L, Nielsen E B, Schmidt K, Mayer B.
Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one.
Mol Pharmacol.
1995;
48
184-8
-
16
Bussemaker E, Popp R, Fisslthaler B, Larson C M, Fleming I, Busse R. et al .
Aged spontaneously hypertensive rats exhibit a selective loss of EDHF-mediated relaxation in the renal artery.
Hypertension.
2003;
42
562-8
-
17
Ulker S, McMaster D, McKeown P P, Bayraktutan U.
Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation.
Cardiovasc Res.
2003;
59
488-500
-
18
Luo X P, Shi H M, Zeng Z Y, Fan W H, Dai R H.
Effect of Astragalus membranaceus on post-infarction function and remodeling of left ventricle.
Chin J Pathophysiol.
1999;
15
639-42
-
19
Shi G G, Chen J C, Li Z C, Liu X P.
Direct effect of Astragalus membranaceus on coronary artery.
Trad Chin Drug Res Clin Pharmacol.
1999;
10
38-9
-
20
Zhang B Q, Sun J, Hu S J, Shan Q X, Xia Q.
Astragalus membranaceus induced endothelium-dependent vasomotor effect and its mechanism in rat thoracic aorta.
Chin J Pharmacol Toxicol.
2005;
19
44-8
-
21
Quan J, Du G.
Protective effect of Astragalus membranaceus (Fisch.) Bge. and Hedysarum polybotrys Hand.-Mazz. on experimental model of cerebral ischemia in rats.
China J Chin Mater Med.
1998;
23
371-3
-
22
Chen L X, Liao J Z, Guo W Q.
Effects of Astragalus membranaceus on left ventricular function and oxygen free radical in acute myocardial infarction patients and mechanism of its cardiotonic action.
Chin J Integr Trad Western Med.
1995;
15
141-3
-
23
Li S Q, Yuan R X, Gao H, Wang Y Q.
Clinical observation on treatment of ischemic heart disease with Astragalus membranaceus
.
Chin J Integr Trad Western Med.
1995;
15
77-80
-
24
Zhou S N, Shao W, Zhang W G, Lu X Y, Yu S Q.
Clinical study of Astragalus membranaceus injection on protecting myocardial ischemia-reperfusion injury.
Chin J Integr Trad Western Med.
2000;
7
168-70
Wei-Dong Zhang
Department of Natural Medicinal Chemistry
School of Pharmacy
Second Military Medical University
325 Guohe Rd.
Shanghai 200433
People’s Republic of China
Phone: +86-21-2507-0386
Fax: +86-21-2507-0386
Email: WDZhangY@hotmail.com
