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The Connexin40 A96S Mutation Causes Renin-Dependent Hypertension
- Source :
- Journal of the American Society of Nephrology. 22:1031-1040
- Publication Year :
- 2011
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2011.
-
Abstract
- Deletion of the gap-junction-forming protein connexin40 leads to renin-dependent hypertension in mice, but whether observed human variants in connexin40, such as A96S, promote hypertension is unknown. Here, we generated mice with the A96S variant in the mouse connexin40 gene. Although mice homozygous for the A96S mutations had normal expression patterns of connexin40 in the kidney, they were hypertensive, had sixfold higher plasma renin concentrations, and had 40% higher levels of renin mRNA than controls. Renin-expressing cells were aberrantly located outside the media layer of afferent arterioles, and increased renal perfusion pressure did not inhibit renin secretion from kidneys isolated from homozygous A96S mice. Treatment with a low-salt diet in combination with an ACE inhibitor increased renin mRNA levels, plasma renin concentrations, and the number of aberrantly localized renin-producing cells. Taken together, these findings suggest that the A96S mutation in connexin40 leads to renin-dependent hypertension in mice. Modulation of renin secretion by BP critically depends on functional connexin40; with the A96S mutation, the aberrant extravascular localization of renin-secreting cells in the kidney likely impairs the pressure-mediated inhibition of renin secretion.
- Subjects :
- Nephrology
medicine.medical_specialty
Afferent arterioles
Angiotensin-Converting Enzyme Inhibitors
Mice, Transgenic
Biology
Transfection
medicine.disease_cause
Plasma renin activity
Connexins
Mice
Internal medicine
Renin
Renin–angiotensin system
medicine
Animals
Humans
Kidney
Mutation
Gap Junctions
General Medicine
Diet, Sodium-Restricted
Mice, Inbred C57BL
Disease Models, Animal
Treatment Outcome
Basic Research
medicine.anatomical_structure
Endocrinology
Hypertension
ACE inhibitor
Female
HeLa Cells
medicine.drug
Subjects
Details
- ISSN :
- 10466673
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....3a2348c9e5c6d28a795e203248e7583d