Endothelin converting enzyme-1 gene expression in the kidney of spontaneously hypertensive rats.
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.
Disashi
T
T
Third Department of Internal Medicine, Kumamoto University School of Medicine, Japan. duze@kaiju.medic.kumamoto-u.ac.jp
Nonoguchi
H
H
Iwaoka
T
T
Naomi
S
S
Nakayama
Y
Y
Shimada
K
K
Tanzawa
K
K
Tomita
K
K
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
D017931:DNA Primers; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes