title: Alteration of renal adrenomedullin and its receptor system in the severely hypertensive rat: effect of diuretic.
abstract: OBJECTIVE
  We investigated the pathophysiological role of the renal adrenomedullin (AM) system, including the ligand, receptor, and amidating activity, in severe hypertensive rats.
  
  
  METHODS
  We studied three groups: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), and diuretic-treated SHR-SP. We measured AM-mature, active form, and AM-total (active form+inactive form) in plasma and renal tissues, and mRNA levels of AM and AM receptor system components such as calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP) 2, and RAMP3 in renal tissues.
  
  
  RESULTS
  SHR-SP had higher blood pressure, plasma neurohumoral factors, and lower renal function than WKY. SHR-SP had higher AM-mature and AM-total levels in plasma and renal tissues than WKY. Although the plasma AM-mature/AM-total ratio was similar in the two groups, AM-mature/AM-total ratio in renal tissues was higher in SHR-SP than in WKY. In addition, mRNA levels of AM in the renal cortex and medulla and the mRNA levels of CRLR, RAMP2, and RAMP3 in the renal cortex were higher in SHR-SP than in WKY. Chronic diuretic treatment decreased blood pressure and improved kidney function and neurohumoral factors, with reductions in plasma and renal AM system.
  
  
  CONCLUSIONS
  Upregulation of circulating and renal AM system may modulate pathophysiology in SHR-SP.
authors.affiliation: Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. nishikim@dokkyomed.ac.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikimi
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Kazumi
authors.initials: K
authors.lastname: Akimoto
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tadokoro
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Mori
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Ishimura
authors.forename: Fumiki
authors.initials: F
authors.lastname: Yoshihara
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D053607:Adrenomedullin; D000450:Aldosterone / Q000097:blood; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D004232:Diuretics; D008233:Lymphotoxin-alpha; D010455:Peptides; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018000:Receptors, Peptide; D053607:Adrenomedullin; D000450:Aldosterone