ENDOTHELIN-CONVERTING ENZYME-1 GENE-EXPRESSION IN THE KIDNEY OF SPONTANEOUSLY HYPERTENSIVE RATS

Abnormal renal handling of water and sodium is implicated in the patho genesis of hypertension in spontaneously hypertensive rats (SHR). Alte ration of renal endothelin-1 synthesis is also reported in SHR. Endoth elin-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 bo th 4- and 12-week-old SHR and age-matched Wistar-Kyoto rats (WKY) were studied. ECE-1 mRNA in microdissected nephron segments was assessed b y reverse transcription-competitive polymerase chain reaction, and ECE -1 protein level by Western blot. In 4-week-old SHR, ECE-1 mRNA was si gnificantly increased in the proximal straight tubule, medullary thick ascending limb, cortical thick ascending limb, and inner medullary co llecting duct. ECE-1 protein level was increased in both the outer and inner medulla. In 12-week-old SHR, ECE-1 gene expression was signific antly increased in the proximal straight tubule, medullary thick ascen ding limb, and also in the glomeruli. Glomerular preproendothelin-1 mR NA 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 t hat contributes to the development and/or maintenance of hyper tension in SHR.