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KMID : 0811720030070000177
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Korean Journal of Physiology & Pharmacology
2003 Volume.7 No. 0 p.177 ~ p.0
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Hypertension Induced by Renal Collecting Duct-specific Deletion of Endothelin-1 gene
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Ahn Do-Whan
Donald E Kohan
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Abstract
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The renal inner medulla contains higher amount of endothelin-1 (ET-1) compared with other tissues. In an in vitro study ET-1 inhibits Na and water reabsorption in the cortical and medullary collecting ducts. However, its physiological role in vivo remains controversial. We examined the physiological effects of selective deletion of ET-1 gene in the collecting duct of mice. Mice were generated which were heterozygous for a human aquaporin-2 promoter driving Cre recombinase and homozygous for loxP-flanked exon 2 of the ET-1 gene. In situ hybridization revealed the knockout mice had markedly decreased ET-1 mRNA message in the collecting duct yet were histologically normal. ET-1 level in plasma of the knockouts was unchanged but its urinary excretion was decreased (P＜0.08). The ET-1 knockouts were hypertensive (mean arterial BP 130.8±2.0 mmHg vs. 109.8±2.7 in floxed controls) and had higher pulse rate compared with controls. They also had reduced urine volume, elevated urine osmolality and had decreased urinary excretion of sodium and total osmolar substances, but not potassium. Creatinine clearance was unaffected. The concentrations of plasma electrolytes and hormones such as ADH, angiotensin II were not different. These results indicate that deficiency of collecting duct-derived ET-1 causes hypertension that is associated with renal sodium and water retension.
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KEYWORD
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Hypertension, Endothelin-1, Knockout, Collecting duct
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