Shengmai Suppressed Vascular Tension in Umbilical Arteries and Veins of Human and Sheep


Objective—The umbilical cord is a critical pathway between mothers and fetuses, and regulations of umbilical vessel tension are important for fetal growth. Shengmai is an herbal medicine being used in treatments of cardiovascular diseases. However, effects of Shengmai on human blood vessels and related pharmacological mechanisms are unclear. Methods—This study investigated the effects of related mechanisms of Shengmai and its key compounds on human and sheep umbilical arteries and veins using organ bath systems. Key Findings—Shengmai significantly suppressed phenylephrine-stimulated vasoconstriction in umbilical arteries and veins. NG-Nitro-L-arginine Methyl Estercould not change the Shengmai-suppressed vasoconstriction in human and sheep umbilical vessels. Among four key compounds of Shengmai, Ginsenoside Re, Ginsenoside Rb1, Ginsenoside Rg1, and Schisandrin, only Ginsenoside Re showed the significant effect similar to Shengmai’s in the umbilical vessels. In Ca2+-free solution, Ginsenoside Re did not affect vasoconstriction. In addition, caffeine- or phenylephrine-stimulated vasoconstriction were not changed by Ginsenoside Re. Either charybdotoxin or glibenclamide could inhibit Ginsenoside Re-caused inhibition of the stimulated vasoconstriction in both human and sheep umbilical vessels, where 4-aminopyridine did not show the similar inhibitory effect. Conclusion—The results provide new information on Shengmai’s effects and underlying mechanisms in umbilical vessels. Importantly, the information gained offers interesting potential for developing new drugs acting on umbilical cords for fetal medicine.

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Yin, X. , Gu, X. , He, Y. , Zhu, D. , Chen, J. , Wu, J. , Feng, X. , Li, J. , Mao, C. and Xu, Z. (2015) Shengmai Suppressed Vascular Tension in Umbilical Arteries and Veins of Human and Sheep. Pharmacology & Pharmacy, 6, 281-291. doi: 10.4236/pp.2015.66030.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Antoniou, E.E., Derom, C., Thiery, E., Fowler, T., Southwood, T.R. and Zeegers, M.P. (2011) The Influence of Genetic and Environmental Factors on the Etiology of the Human Umbilical Cord: The East Flanders Prospective Twin Survey. Biology of Reproduction, 85, 137-143.
[2] Imamura, T., Potempa, J. and Travis, J. (2004) Activation of the Kallikrein-Kinin System and Release of New Kinins through Alternative Cleavage of Kininogens by Microbial and Human Cell Proteinases. Biological Chemistry, 385, 989-996.
[3] Ferguson, V.L. and Dodson, R.B. (2009) Bioengineering Aspects of the Umbilical Cord. European Journal of Obstetrics & Gynecology, 144, S108-S113.
[4] Whitehead, C.L., Teh, W.T., Walker, S.P., Leung, C., Larmour, L. and Tong, S. (2013) Circulating MicroRNAs in Maternal Blood as Potential Biomarkers for Fetal Hypoxia in-Utero. PLoS ONE, 8, e78487.
[5] Smith, G.C. and Fretts, R.C. (2007) Stillbirth. The Lancet, 370, 1715-1725.
[6] Froen, J.F., Gardosi, J.O., Thurmann, A., Francis, A. and Stray-Pedersen, B. (2004) Restricted Fetal Growth in Sudden Intrauterine Unexplained Death. Acta Obstetricia et Gynecologica Scandinavica, 83, 801-807.
[7] Lawn, J.E., Cousens, S. and Zupan, J. (2005) 4 Million Neonatal Deaths: When? Where? Why? The Lancet, 365, 891-900.
[8] Nishida, H., Kushida, M., Nakajima, Y., Ogawa, Y., Tatewaki, N., Sato, S., et al. (2007) Amyloid-Beta-Induced Cytotoxicity of PC-12 Cell Was Attenuated by Shengmai-San through Redox Regulation and Outgrowth Induction. Journal of Pharmacological Sciences, 104, 73-81.
[9] Wang, N.L., Liou, Y.L., Lin, M.T., Lin, C.L. and Chang, C.K. (2005) Chinese Herbal Medicine, Shengmai San, Is Effective for Improving Circulatory Shock and Oxidative Damage in the Brain during Heatstroke. Journal of Pharmacological Sciences, 97, 253-265.
[10] Zhao, M.H., Rong, Y.Z. and Lu, B.J. (1996) [Effect of Shengmaisan on Serum Lipid Peroxidation in Acute Viral Myocarditis]. Chinese Journal of Integrated Traditional and Western, 16, 142-145.
[11] Fang, J., Jiang, J. and Luo, D.C. (1987) [Effect of Sheng Mai Decoction on Left Ventricular Function in Patients with Coronary Heart Disease. A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial]. Chinese Journal of Internal Medicine, 26, 403-406.
[12] Zhan, S., Guo, W., Shao, Q., Fan, X., Li, Z. and Cheng, Y. (2014) A Pharmacokinetic and Pharmacodynamic Study of Drug-Drug Interaction between Ginsenoside Rg1, Ginsenoside Rb1 and Schizandrin after Intravenous Administration to Rats. Journal of Ethnopharmacology, 152, 333-339.
[13] Hehir, M.P., Moynihan, A.T., Glavey, S.V. and Morrison, J.J. (2009) Umbilical Artery Tone in Maternal Obesity. Reproductive Biology and Endocrinology, 7, 6.
[14] Pujol Lereis, V.A., Hita, F.J., Gobbi, M.D., Verdi, M.G. and Rodriguez, M.C. (2006) Rothlin RP. Pharmacological Characterization of Muscarinic Receptor Subtypes Mediating Vasoconstriction of Human Umbilical Vein. British Journal of Pharmacology, 147, 516-523.
[15] Errasti, A.E., Velo, M.P., Torres, R.M., Sardi, S.P. and Rothlin, R.P. (1999) Characterization of Alpha1-Adrenoceptor Subtypes Mediating Vasoconstriction in Human Umbilical Vein. British Journal of Pharmacology, 126, 437-442.
[16] Dennedy, M.C., Houlihan, D.D., McMillan, H. and Morrison, J.J. (2002) β2- and β3-Adrenoreceptor Agonists: Human Myometrial Selectivity and Effects on Umbilical Artery Tone. American Journal of Obstetrics and Gynecology, 187, 641-647.
[17] Potter, S.M., Dennedy, M.C. and Morrison, J.J. (2002) Corticosteroids and Fetal Vasculature: Effects of Hydrocortisone, Dexamethasone and Betamethasone on Human Umbilical Artery. BJOG: An International Journal of Obstetrics & Gynaecology, 109, 1126-1131.
[18] Topal, G., Foudi, N., Uydes-Dogan, B.S., Cachina, T., Kucur, M., Gezer, A., et al. (2010) Involvement of Prostaglandin F2alpha in Preeclamptic Human Umbilical Vein Vasospasm: A Role of Prostaglandin F and Thromboxane A2 Receptors. Journal of Hypertension, 28, 2438-2445.
[19] Lam, F.F., Deng, S.Y., Ng, E.S., Yeung, J.H., Kwan, Y.W., Lau, C.B., et al. (2010) Mechanisms of the Relaxant Effect of a Danshen and Gegen Formulation on Rat Isolated Cerebral Basilar Artery. Journal of Ethnopharmacology, 132, 186-192.
[20] Nelson, M.T. and Quayle, J.M. (1995) Physiological Roles and Properties of Potassium Channels in Arterial Smooth Muscle. American Journal of Physiology, 268, C799-C822.
[21] Gao, W., Dong, X., Xie, N., Zhou, C., Fan, Y., Chen, G., et al. (2014) Dehydroabietic Acid Isolated from Commiphora opobalsamum Causes Endothelium-Dependent Relaxation of Pulmonary Artery via PI3K/Akt-eNOS Signaling Pathway. Molecules, 19, 8503-8517.
[22] Gauthier, K.M., Campbell, W.B. and McNeish, A.J. (2014) Regulation of KCa2.3 and Endothelium-Dependent Hyperpolarization (EDH) in the Rat Middle Cerebral Artery: The Role of Lipoxygenase Metabolites and Isoprostanes. PeerJ, 2, e414.
[23] Shamsuzzaman, A.S., Gersh, B.J. and Somers, V.K. (2003) Obstructive Sleep Apnea: Implications for Cardiac and Vascular Disease. The Journal of the American Medical Association, 290, 1906-1914.
[24] Phillips, B.G., Narkiewicz, K., Pesek, C.A., Haynes, W.G., Dyken, M.E. and Somers, V.K. (1999) Effects of obstructive Sleep Apnea on Endothelin-1 and Blood Pressure. Journal of Hypertension, 17, 61-66.
[25] Allahdadi, K.J., Walker, B.R. and Kanagy, N.L. (2005) Augmented Endothelin Vasoconstriction in Intermittent Hypoxia-Induced Hypertension. Hypertension, 45, 705-709.
[26] Sumpio, B.E., Riley, J.T. and Dardik, A. (2002) Cells in Focus: Endothelial Cell. The International Journal of Biochemistry & Cell Biology, 34, 1508-1512.
[27] Wang, L., Zhang, Y., Wang, Z., Li, S., Min, G., Chen, J., et al. (2012) Inhibitory Effect of Ginsenoside-Rd on Carrageenan-Induced Inflammation in Rats. Canadian Journal of Physiology and Pharmacology, 90, 229-236.
[28] Kou, J., Tian, Y., Tang, Y., Yan, J. and Yu, B. (2006) Antithrombotic Activities of Aqueous Extract from Radix Ophiopogon Japonicus and Its Two Constituents. Biological and Pharmaceutical Bulletin, 29, 1267-1270.
[29] Chiu, P.Y., Luk, K.F., Leung, H.Y., Ng, K.M. and Ko, K.M. (2008) Schisandrin B Stereoisomers Protect against Hypoxia/Reoxygenation-Induced Apoptosis and Inhibit Associated Changes in Ca2+-Induced Mitochondrial Permeability Transition and Mitochondrial Membrane Potential in H9c2 Cardiomyocytes. Life Sciences, 82, 1092-1101.
[30] Chai, H., Wang, Q., Huang, L., Xie, T. and Fu, Y. (2008) Ginsenoside Rb1 Inhibits Tumor Necrosis Factor-Alpha-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells. Biological and Pharmaceutical Bulletin, 31, 2050-2056.
[31] Yim, T.K. and Ko, K.M. (1999) Methylenedioxy Group and Cyc-looctadiene Ring as Structural Determinants of Schisandrin in Protecting against Myocardial Ischemia-Reperfusion Injury in Rats. Biochemical Pharmacology, 57, 77-81.
[32] Fong, W.F., Wan, C.K., Zhu, G.Y., Chattopadhyay, A., Dey, S., Zhao, Z., et al. (2007) Schisandrol A from Schisandra Chinensis Reverses P-Glycoprotein-Mediated Multidrug Resistance by Affecting Pgp-Substrate Complexes. Planta Medica, 73, 212-220.
[33] Pan, Q., Lu, Q., Zhang, K. and Hu, X. (2006) Dibenzocyclooctadiene Lingnans: A Class of Novel Inhibitors of P-Glycoprotein. Cancer Chemotherapy and Pharmacology, 58, 99-106.
[34] Ito, S., Suki, B., Kume, H., Numaguchi, Y., Ishii, M., Iwaki, M., et al. (2010) Actin Cytoskeleton Regulates Stretch-Activated Ca2+ Influx in Human Pulmonary Microvascular Endothelial Cells. American Journal of Respiratory Cell and Molecular Biology, 43, 26-34.
[35] van Kesteren, R.E. and Geraerts, W.P. (1998) Molecular Evolution of Ligand-Binding Specificity in the Vasopressin/Oxytocin Receptor Family. Annals of the New York Academy of Sciences, 839, 25-34.
[36] Rembold, C.M. (1992) Regulation of Contraction and Relaxation in Arterial Smooth Muscle. Hypertension, 20, 129-137.
[37] Ives, S.J., Andtbacka, R.H., Kwon, S.H., Shiu, Y.T., Ruan, T., Noyes, R.D., et al. (2012) Heat and Alpha1-Adrenergic Responsiveness in Human Skeletal Muscle Feed Arteries: The Role of Nitric Oxide. Journal of Applied Physiology, 113, 1690-1698.
[38] Striessnig, J., Pinggera, A., Kaur, G., Bock, G. and Tuluc, P. (2014) L-type Ca Channels in Heart and Brain. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling, 3, 15-38.
[39] Hermsmeyer, K., Sturek, M. and Rusch, N.J. (1988) Calcium Channel Modulation by Dihydropyridines in Vascular Smooth Muscle. Annals of the New York Academy of Sciences, 522, 25-31.
[40] Connolly, M.J., Prieto-Lloret, J., Becker, S., Ward, J.P. and Aaronson, P.I. (2013) Hypoxic Pulmonary Vasoconstriction in the Absence of Pretone: Essential Role for Intracellular Ca2+ Release. The Journal of Physiology, 591, 4473-4498.
[41] Perez, C.G., Copello, J.A., Li, Y., Karko, K.L., Gomez, L., Ramos-Franco, J., et al. (2005) Ryanodine Receptor Function in Newborn Rat Heart. American Journal of Physiology-Heart and Circulatory Physiology, 288, H2527-H2540.
[42] Navarro-Dorado, J., Garcia-Alonso, M., van Breemen, C., Tejerina, T. and Fameli, N. (2014) Calcium Oscillations in Human Mesenteric Vascular Smooth Muscle. Biochemical and Biophysical Research Communications, 445, 84-88.
[43] Cribbs, L.L. (2006) T-Type Ca2+ Channels in Vascular Smooth Muscle: Multiple Functions. Cell Calcium, 40, 221-230.
[44] Jackson, W.F. (2000) Ion Channels and Vascular Tone. Hypertension, 35, 173-178.

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