Increased renal medullary endothelin-1 synthesis in prehypertensive DOCA- and salt-treated rats.
To investigate the role of renal endothelin-1 (ET-1) synthesis in water-sodium homeostasis, we measured mRNA expressions, protein levels, enzyme activity, and receptor binding of the renal ET-1 system in a DOCA- and salt-treated rat model. Male Wistar rats were divided into control and DOCA- and salt-treated (DOCA-Salt) groups. The DOCA-Salt group received 25 mg/kg body wt DOCA and was maintained on 1% NaCl drinking water. Rats were killed on days 1, 2, 4, and 10 of the experiment. Urinary ET-1-like immunoreactivity significantly increased from the second day in the DOCA-Salt group and correlated well with the urinary sodium excretion rate (r = 0.81, P < 0.001). Renal endothelin-converting enzyme (ECE) activity, ET-1, and ECE-1 mRNA expressions were significantly increased in the renal medullary area of DOCA-Salt rats. In situ hybridization and immunohistochemical studies showed that the increase in ET-1 synthesis was mainly localized in the inner medullary collecting ducts. The maximum binding of endothelin B receptor also increased from the second day in the renal medulla of the DOCA-Salt group. Our results suggest that renal medullary synthesized ET-1 may be a natriuretic factor and may participate in the intrarenal regulation of water and salt homeostasis in prehypertensive DOCA-and salt-treated rats.
Hsieh
T J
TJ
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80317, Taiwan. hsiehjun@ms4.ninet.net
Lin
S R
SR
Lee
Y J
YJ
Shin
S J
SJ
Lai
Y H
YH
Hsu
C H
CH
Tsai
J H
JH
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000652:urine; D000072396:Endothelin-Converting Enzymes; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007679:Kidney Medulla / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D014882:Water-Electrolyte Balance / Q000187:drug effects
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D016282:Aspartic Acid Endopeptidases; D012083:Renin; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes