NDLI: Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ramkumar, Nirupama Stuart, Deborah Rees, Sara Hoek, Alfred Van Sigmund, Curt D. Kohan, Donald E.
Description	Author Affiliation: Ramkumar N ( Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City, Utah); Stuart D ( Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City, Utah); Rees S ( Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City, Utah); Hoek AV ( Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City, Utah); Sigmund CD ( Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.); Kohan DE ( Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City, Utah)
Abstract	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.
File Format	HTM / HTML
ISSN	1931857X
e-ISSN	15221466
DOI	10.1152/ajprenal.00367.2014
Journal	AJP: Renal Physiology
Issue Number	8
Volume Number	307
Language	English
Publisher	American Physiological Society
Publisher Date	2014-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Blood Pressure Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Kidney Tubules, Collecting Biosynthesis Kidney Blood Discipline Physiology Epithelial Sodium Channels Renin Hypertension Urine Mice, Inbred C57bl Rna, Messenger Discipline Nephrology Pharmacology Metabolism Sodium Chloride, Dietary Drug Effects Physiopathology Mice, Knockout Animals Angiotensin Ii
Content Type	Text
Resource Type	Article
Subject	Physiology Urology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Cyp2c44 epoxygenase in the collecting duct is essential for the high $K^{+}$ intake-induced antihypertensive effect

Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension

Renal Tubule Angiotensin II Type 1 Receptor–Associated Protein Promotes Natriuresis and Inhibits Salt‐Sensitive Blood Pressure Elevation

Renal salt wasting and chronic dehydration in claudin-7-deficient mice

Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal $Na^{+}$ and water excretion or arterial pressure

Genetic deletion of AT1a receptors attenuates intracellular accumulation of ANG II in the kidney of AT1a receptor-deficient mice.

Effect of aldosterone on BK channel expression in mammalian cortical collecting duct

Mice heterozygous for β-ENaC deletion have defective potassium excretion

Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention.

Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension

Similar Documents

Cyp2c44 epoxygenase in the collecting duct is essential for the high $K^{+}$ intake-induced antihypertensive effect

Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension

Renal Tubule Angiotensin II Type 1 Receptor–Associated Protein Promotes Natriuresis and Inhibits Salt‐Sensitive Blood Pressure Elevation

Renal salt wasting and chronic dehydration in claudin-7-deficient mice

Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal $Na^{+}$ and water excretion or arterial pressure

Genetic deletion of AT1a receptors attenuates intracellular accumulation of ANG II in the kidney of AT1a receptor-deficient mice.

Effect of aldosterone on BK channel expression in mammalian cortical collecting duct

Mice heterozygous for β-ENaC deletion have defective potassium excretion

Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention.

Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension