Abstract 040: Upregulation Of Cyp Epoxygenase In The Connecting Tubule(cnt)/cortical Collecting Duct (ccd) Is Essential For High Potassium (k) Intake-induced Antihypertensive Effect
Cyp epoxygenase is responsible for metabolizing arachidonic acid to epoxyeicosatrienoic acid (EET) in the kidney and vascular tissues. EET has been shown to cause vasodilation by stimulating Ca2+-activated K channels in vascular smooth muscles and to have natriuretic effect by inhibiting the epithelial Na channel (ENaC) in the kidney. In the present study we used real time PCR technique to examine the effect of high salt intake or high K intake on Cyp2c44 (a major type of Cyp epoxygenase in the mouse kidney) in the proximal tubule (PxT), thick ascending limb (TAL), distal convoluted tubule (DCT) and the CNT/CCD. An increase in dietary Na content stimulates the expression of Cyp2c4 in TAL, DCT and CNT/CCD but not in PxT while an increase in dietary K intake augments the expression of Cyp2c44 only in DCT and CNT/CCD. Neither high salt intake nor high K intake has a significant effect on the blood pressure (BP) in wt mice. However, high K intake increased BP in CNT/CCD specific conditional knockout (KO) mice. In contrast, the high Na intake did not significantly increase the BP in those KO mice. This suggests that Cyp2c44 in the CNT/CCD plays a key role in preventing hypertension induced by increasing dietary K intake. Administration of amiloride (a ENaC inhibitor) restored the normal BP in KO mice fed high K diet, suggesting that down-regulation of Cyp2c44 may enhance the Na absorption in the CNT/CCD. This notion was also supported by metabolic cage study demonstrating that renal Na excretion was compromised in KO mice. We conclude that Cyp2c44 plays a key role in stimulating renal Na excretion during increasing dietary K intake and that Cyp-epoxygenase is required for antihypertensive effect induced by high K intake.
- © 2013 by American Heart Association, Inc.