title: Endothelin converting enzyme-1 gene expression in the kidney of spontaneously hypertensive rats.
abstract: Abnormal renal handling of water and sodium is implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). Alteration of renal endothelin-1 synthesis is also reported in SHR. Endothelin-1, a potent vasoconstrictor and regulator of sodium reabsorption in the nephron, has a pathophysiological potential in the development of hypertension. Because synthesis of bioactive endothelin-1 requires endothelin converting enzyme-1 (ECE-1), we investigated whether renal ECE-1 gene expression is altered in the kidney of SHR. Kidneys from both 4- and 12-week-old SHR and age-matched Wistar-Kyoto rats (WKY) were studied. ECE-1 mRNA in microdissected nephron segments was assessed by reverse transcription-competitive polymerase chain reaction, and ECE-1 protein level by Western blot. In 4-week-old SHR, ECE-1 mRNA was significantly increased in the proximal straight tubule, medullary thick ascending limb, cortical thick ascending limb, and inner medullary collecting duct. ECE-1 protein level was increased in both the outer and inner medulla. In 12-week-old SHR, ECE-1 gene expression was significantly increased in the proximal straight tubule, medullary thick ascending limb, and also in the glomeruli. Glomerular preproendothelin-1 mRNA expression was not different between the two strains at both 4 and 12 weeks. We conclude that high ECE-1 gene expression in the nephron, via increase of endothelin-1 synthesis, may promote sodium retention that contributes to the development and/or maintenance of hypertension in SHR.
authors.affiliation: Third Department of Internal Medicine, Kumamoto University School of Medicine, Japan. duze@kaiju.medic.kumamoto-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Disashi
authors.forename: H
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: T
authors.initials: T
authors.lastname: Iwaoka
authors.forename: S
authors.initials: S
authors.lastname: Naomi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: K
authors.initials: K
authors.lastname: Tanzawa
authors.forename: K
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000375:Aging; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D017931:DNA Primers; D000072396:Endothelin-Converting Enzymes; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics; D007668:Kidney / Q000201:enzymology* / Q000254:growth & development; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D008666:Metalloendopeptidases; D016133:Polymerase Chain Reaction; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
chemical_list: D017931:DNA Primers; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes