%0 Journal Article %T Effects of continuous intermedin infusion on blood pressure and hemodynamic function in spontaneously hypertensive rats
%A Ying Yuan %A Xi Wang %A Qiang Zeng %A Hong-Mei Wu %A Yong-Fen Qi %A Chao-Shu Tang %A
%J 老年心脏病学杂志(英文版) %D 2012 %I Science Press %X Objective To examine the effects of exogenously administered intermedin (IMD, adrenomedullin-2) on arterial blood pressure, cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms. Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n = 12), SHR group (n = 12), IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour, n = 12), and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour, n = 12). Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure, the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax), left ventricular systolic pressure and heart rate in SHRs. Furthermore, IMD also inhibited protein over-expression of cardiovascular IMD receptors, myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2), aortic RAMP1, RAMP2, RAMP3, and calcitonin receptor-like receptor (CRLR); suppressed up-regulation of aortic RAMP1, RAMP2, RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP). Additionally, IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration. Conclusion These findings support the speculation that IMD, as a cardiovascular active peptide, is involved in blood pressure reduction and cardiac function amelioration during hypertension. The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR, and consequential regulation of cAMP levels and other cardiovascular active factors, such as ANP and BNP. %K Intermedin %K Receptor activity-modifying proteins %K Calcitonin receptor-like receptor %K Mini-osmotic pumps %K Hemodynamic parameters %K Spontaneously hypertensive rats
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=A9DB1C13C87CE289EA38239A9433C9DC&cid=AD36F34DDC3BA7B0&jid=4DC702B3A2386A4814E2FF9CFB799B27&aid=814899B78B44FD1FE003382C573FFBDD&yid=99E9153A83D4CB11&vid=9CF7A0430CBB2DFD&iid=CA4FD0336C81A37A&sid=BCA2697F357F2001&eid=DB817633AA4F79B9&journal_id=1671-5411&journal_name=Journalofgeriatriccardiology:JGC&referenced_num=0&reference_num=0