Collecting duct specific knock-out of renin attenuates angiotensin-II induced hypertension.

Collecting duct specific knock-out of renin attenuates angiotensin-II induced hypertension. Am J Physiol Renal Physiol. 2014 Aug 13; Authors: Ramkumar N, Stuart D, Rees S, Van Hoek AN, Sigmund CD, Kohan DE Abstract The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined blood pressure and renal salt and water excretion. Mice containing loxP-flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin-2-Cre recombinase to achieve CD-specific renin KO. Compared to controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400ng/kg/min resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 ± 4 mmHg in KO vs 128 ± 3 mmHg in controls). Urinary renin excretion and remained significantly lower in the KO mice following Ang-II infusion as compared to controls. Further, membrane associated ENaC protein levels were s...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research