Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat.

PloS One
Ali AshekMatthew A Bailey

Abstract

Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage). Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP) rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ≈ 20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor ...Continue Reading

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Citations

Apr 11, 2014·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Lenka HoškováLibor Kopkan
Nov 21, 2012·Current Opinion in Nephrology and Hypertension·Nils van der LubbeEwout J Hoorn
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Sep 24, 2019·Frontiers in Pharmacology·Robert M Rapoport, Manoocher Soleimani
Nov 27, 2015·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kathryn R WalshRichard David Wainford

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Methods Mentioned

BETA
transgenic
urine collection
urine collections

Software Mentioned

ImageJ
Art

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