Study of 17 β-Estradiol supplementation on increasing eNOS expression and NO production in ovariectomized rat heart

Abstract

Abstract: AIM: To investigate whether 17β-estradiol influences the production of nitric oxide (NO) and expression of eNOS in ovariectomized (OVX) rats heart. METHODS: Female mature Sprague–Dawley rats were subjected to a bilateral ovariectomy, and sham operation as control.OVX rats were randomly assigned to the following treatments:17β-estradiol (100 μg·kg^-1 in 100 μl sesame oil sc daily), 17β-estradiol vehicle (100 μl sesame oil sc daily) and OVX control.The treatment lasted 6 weeks.Blood pressure, heart rate, plasma estradiol, uterine weights and nitrite production in the myocardium were studied.Western blot analysis was used to assay the protein expression of eNOS and caveolin-1.RESULTS: The heat rates in 17β-estradiol treatment group (314 ±16 beats·min^-1) were lower than those in other groups (P <0.05).Compared with vehicle group, nitrite production increased one fold in the hearts of E2 treatment group, the abundance of eNOS protein showed a significant increase (P <0.01).Concurrently caveolin-1 protein, an endogenous eNOS inhibitor, protein expression abundance was significantly decreased (P <0.05) in the E2 supplement group.CONCLUSION: Estrogen supplementation directly increases eNOS functional activity and NO production in rat heart, this effect may be related to estrogen-induced deceasing of heart rates.

Key words: 17β-estradiol, nitric oxide, endothelial nitric oxide synthase, caveolin

CLC Number:

R965.1
R963

TANG Yong-Bo, WANG Qian-Lei, ZHU Bing-Yang, HUANG Hong-Lin, LIAO Duan-Fang. Study of 17 β-Estradiol supplementation on increasing eNOS expression and NO production in ovariectomized rat heart[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(4): 411-416.

References

1 Mendelsohn ME, Karas RH.The protective effects of estrogen on the cardiovascular sy stem[J].N Engl J Med, 1999;340 (23):1801-11
2 Chambliss KL, Shaul PW.Estrogen modulation of endothelial nitric oxide synthase[J].Endocrine Reviews, 2002;23(5):665-86
3 Rossouw JE.Effect of postmenopausal hormone therapy on cardiovascular risk[J].J Hypertens, 2002;20(2):S62-5
4 Giraldez RR, Panda A, Zweier JL.Endothelial dysfunction does not require loss of endothelial nitric oxide synthase[J].Am J Physiol, 2000;278(6):H2020-7
5 Cherney A, Edgell H, Krukoff TL.NO mediates effects of estrogen on central regulation of blood pressure in restrained, ovariectomized rats[J].Am J Physiol, 2003;285(4):R842-9
6 Dubey RK, Jackson EK.Estrogen-induced cardiorenal protection:potential cellular, biochemical, and molecularmechanisms [J].Am J Physiol, 2001;280(3):F365-88
7 Chambliss KL, Yuhanna IS, Mineo C, Liu P, German Z, Sherman TS, et al.Estrogen receptor αand endothelial nitric oxide synthase are organized into a functional signaling molecule in caveolae[J].Circ Res, 2000;87(11):E44-52
8 Mohamed MK, El-Mas MM, Abdel-Rahman AA.Estrogen enhancement of baroreflex sensitivity is centrally mediated[J].Am J Physiol, 1999;276(4):R1030-7
9 Wang X, Abdel AR.Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in the rats hearts [J].Am J Physiol, 2002;282(6):2309-15
10 JankowskiM, Rachelska G, Donghao W, McCann SM, Gutkowska J.Estrogen receptors activate atrial natriuretic peptide in the rat heart[J].Proc Natl Acad Sci USA, 2001;98(20): 11765-70
11 JayachandranM, Hayashi T, Sumi D, Iguchi A, Miller VM. Temporal effects of estradiol on caveolin-1 mRNA and protein in bovine aortic endothelial cells[J].Am J Physiol, 2001;281 (3):H1327-33
12 Xu HL, Galea E, Santizo RA, Baughman VL, Pelligrino DA. The key role of caveolin-1 in estrogen-mediated regulation of endothelial nitric oxide synthase function in cerebral arterioles in vivo[J].J Cereb Blood Flow Metab, 2001;21(8):907-13
13 MacRitchie AN, Jun SS, Chen Z, German Z, Yuhanna IS, Sherman TS, et al.Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal pulmonary endothelium [J].Circ Res, 1997;81(3):355-62
14 Shaul PW.Regulation of endothelial nitric oxide synthase:Location, Location, Location[J].Annu Rev Physiol, 2002;64 (3):749-74
15 BentenWP, Stephan C, Lieberherr M, Wunderlich F.Estradiol signaling via sequestrable surface receptors[J].Endocrinology, 2001;142(4):1669-77
16 Knauf C, Ferreira S, Hamdane M, Mailliot C, Prevot V, Beauvillain JC, et al.Variation of endothelial nitric oxide synthase synthesis in the median eminence during the rat estrous cycle:an additional argument for the implication of vascular blood vessel in the control of GnRH release[J].Endocrinology, 2001;142(10):4288-419
17 Pelligrino DA, Ye S, Tan F, Santizo RA, Feinstein DL, Wang Q.Nitric oxide-dependent pial arteriolar dilation in the famal rat:effects of chronic estrogen depletion and repletion[J].Biochem Biophys Res Commun, 2000;269(1):165-71
18 Santizo RA, Xu HL, Galea E, Muyskens S, Baughman VL, Pelligrino DA.Combined endothelial nitric oxide synthase upregulation and caveolin-1 downregulation decrease leukocyte adhesion in pial venules of ovariectomized female rats[J].Stroke, 2002;33(2):613-6
19 Shah V, Toruner M, Haddad F, Cadelina G, Papapetropoulos A, Choo K, et al.Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat[J].Gastroenterology, 1999;117(5): 1222-8

[1]	WANG Rongjun, DING Bo. Mechanism of human urotensin II on myocardial ischemia-reperfusion injury in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(6): 622-626.
[2]	ZENG Wei-xian, DAI Yuan-rong. Prevention by caveolin-1 of the proliferation of the asthmatic airway smooth muscle cells is most likely mediated by ERK1/2 signal pathway and regulation of roxithromycin [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(6): 632-638.
[3]	QIAN Xiao-dan, LUO Chun-xia, ZHU Dong-ya. nNOS is required for enhancing proliferation of NSCs induced by OGD [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(10): 1099-1106.
[4]	JIN Wan-bing. Protective effects of puerarin on gentamicin-induced nephrotoxicity in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(8): 864-867.
[5]	FANG Chao, ZENG Hui, ZHOU Hong-Hao, LIU Zhao-Qian. Research progress on relationship between eNOS and ACE gene polymorphisms and coronary heart disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(2): 222-228.
[6]	TUO Qin-hui, YUAN Hao-yu, GUO Yan, YU Wei-xia , LIAO Duan-fang. Ezetimibe inhibiting intracellular lipid accumulation through caveolin-1 in rat vascular smooth muscle cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(5): 492-495.
[7]	SUN Chuan-bo,GAO Jing-hong, HU Liang, ZHANG Jing-wen, WEI Li, LI Qing-ping. High glucose-induced apoptosis of H9c2 cells is closely related to GAPDH nuclear translocation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(4): 374-379.
[8]	MIAO Jing-kun, CHEN Qi-xiong, WU Xiao-mei, LIU Zhen-qiu, ZHANG Xiao-ping. Effects of compound decotion on activity and expression of nitric oxide and neuronal nitric oxide synthase in the brain of traumatic brain injury rat model [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1340-1346.
[9]	WANG Zhan-qing, WANG Jin-ping, XU Jing-feng, ZENG Ming, CHEN Yan. Effects of isosorbide dinitrate on contractions of rat urine bladder destrusor in vitro [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(11): 1248-1251.
[10]	MAO Yao-sheng, CAO miao-ying, ZHOU Xin. Effects of intensive insulin therapy on the prognosis and serum vWF,ET-1 and NO levels in patients with sepsis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(12): 1414-1417.
[11]	YE Hui, YING Xiao-ming, TONG Xia-sheng, CHEN Li-zhong, ZHAO Bei. Effect of budesonide on the expression of inducible nitric oxide synthase at blood heterophil granulocyte in asthma rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(9): 1008-1012.
[12]	LI Heng, SHEN Lin, LI Li-qin, SHUAI Bo, GUO Xiang-hei. Effects of Shaolingxiaozeng Tie on serum levels of NO and MMP-9mRNA in peripheral blood mononuclear cell on knee osteoarthritis patients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(3): 322-327.
[13]	CHEN Cun-guo, JIN Hai-hua, LI Shao-bo, JIN Xiao-hong, CHEN Bao-guo, TONG Xia-sheng, YE Hui. Inducible nitric oxide synthase expression in lung tissue and neutrophil of asthmatic rats and the effects of dexamethasone on them [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(10): 1128-1132.
[14]	XIN Yan-fei, ZHANG Li-li, XUAN Yao-xian. Diphasic action of nitric oxide in doxorubicin-induced cardiotoxicity [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 117-120.
[15]	CHEN Jian-yan, YAO Shang-long, ZHAO Da-zhong, LU Jian-fang. Changes of nNOS mRNA in rabbit brain under different anesthetic depths:using target-controlled infusion of propofol [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(6): 634-638.