International Journal of Innovative Research in Medical Science (IJIRMS) Volume 02 Issue 08 August 2017, ISSN No. - 2455-8737 Available online at - www.ijirms.in 1164 DOI: 10.23958/ijirms/vol02-i08/13 © 2017 Published by IJIRMS Publication Estradiol Down-Regulates Gene Expression of Angiotensin-II Receptor Type One in Ovariectomized Rats Hamed M. Osman 1 , Hanan F. Al-Saeed 1 , Amani M. El Amin Ali *2 , Azza M. Zaki 2 1 Department of Medical Physiology, Faculty of Medicine, Al-Azhar University, Egypt 2 Department of Medical Physiology, Faculty of Medicine, Fayoum University, Egypt * Email: elamin_amani@yahoo.com Abstract: Both estrogen deficiency and activation of renin-angiotensin- aldosterone system (RAAS) are implicated in the development of cardiovascular diseases in postmenopausal women, therefore this study aimed to clarify the influence of estradiol (E2) on expression of angiotensin receptor type one (AT1R) in target tissues of ovariectomized rats and whether it can add to the antihypertensive effects of angiotensin receptor blockers (ARBs). Fifty adult female rats were equally divided into 5 groups: Control group, ovariectomized (OVX) group not receiving any treatment, OVX group treated with conjugated estrogen (premarin), OVX group treated with valsartan and OVX group treated with premarin and valsartan. Treatments started 4 weeks after ovariectomy and continued for 8 weeks. By the end of experiment serum levels of renin, angiotensin-II, aldosterone, Na+ and K+ were measured. Hearts, adrenal glands, and kidneys were removed to quantify the gene expression of AT1R. Ovariectomy resulted in a significant increase in serum concentrations of renin, angiotensin-II, aldosterone, Na+ and AT1R gene expression, as well as a significant decrease in K+ concentration compared to control group. These findings were improved in all groups received either estrogen and/or valsartan. The best results were achieved when both drugs were used together. In conclusion concomitant use of estrogen with ARBs may provide a more effective form of RAAS blockade than the monotherapy of either of them. Keywords: Menopause, Hypertension, Estrogen, RAAS, Valsartan and AT1R. 1. Introduction: Cardiovascular disease is a leading cause of death in postmenopausal women worldwide. [1] It is well known that estrogen deficiency increases the risk of developing hypertension, coronary atherosclerosis, and myocardial infarction in postmenopausal women [2],[3] In addition to estrogen deficiency, another recognized factor implicated in the pathogenesis of hypertension, atherosclerosis, and congestive heart failure is activation of the renin-angiotensin- aldosterone system (RAAS). [4] Angiotensin-II (Ang II) is the principle effector of the renin- angiotensin system that makes critical contributions to the pathogenesis of hypertension, atherosclerosis, vascular and myocardial remodeling, and congestive heart failure. [5] Ang II is also, a potent stimulator of NADPH oxidase, which is the major source and primary trigger for reactive oxygen species (ROS) generation in various tissues. Recently, the importance of oxidative stress in Ang II- induced heart diseases has been confirmed. [4] Recent accumulating evidence has demonstrated that angiotensin receptor type one (AT1R) is the angiotensin receptor involved in most of the classical effects of Ang II such as oxidative stress generation and vasoconstriction. Via these effects ANG-II could induce blood pressure elevation and cardiovascular injury. [6] Accordingly, specific AT1R blockers (ARBs) dramatically lower blood pressure and improve vascular and myocardial function in patients with cardiovascular disease. [7] Therefore, this study was conducted to investigate the influence of estrogen on expression of AT1R in target tissues (heart, kidney and adrenal glands) of ovariectomized rats and whether it can add to the antihypertensive effects of angiotensin receptor blocker. 2. Material and methods Drugs:  Conjugated equine estrogen (Premarin): Premarin tablets (each one containing 0.625 mg of conjugated estrogen) were obtained from Wyeth pharmaceuticals Inc., now a part of Pfizer Open Access Journal Research Article DOI: 10.23958/ijirms/vol02-i08/13