Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat.
The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.
Cao
Yuan-Ning
YN
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Kitamura
Kazuo
K
Kato
Johji
J
Kuwasako
Kenji
K
Ito
Kaoru
K
Onitsuka
Hisamitsu
H
Nagoshi
Yasuko
Y
Uemura
Tomohiko
T
Kita
Toshihiro
T
Eto
Tanenao
T
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D053607:Adrenomedullin; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010455:Peptides / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000187:drug effects
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; C545508:Ramp1 protein, rat; C545509:Ramp2 protein, rat; C545510:Ramp3 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D017673:Sodium Chloride, Dietary; D053607:Adrenomedullin; D000450:Aldosterone