Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension. Am J Physiol Renal Physiol 2014 Oct 15;307(8):F931-8
Date
08/15/2014Pubmed ID
25122048Pubmed Central ID
PMC4200300DOI
10.1152/ajprenal.00367.2014Scopus ID
2-s2.0-84908079996 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP 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 with 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 400 ng·kg(-1)·min(-1) 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 epithelial Na(+) channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane-associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression.
Author List
Ramkumar N, Stuart D, Rees S, Hoek AV, Sigmund CD, Kohan DEAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Blood Pressure
Epithelial Sodium Channels
Female
Hypertension
Kidney
Kidney Tubules, Collecting
Male
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger
Renin
Sodium Chloride, Dietary
