Neuron-specific (pro)renin receptor knockout prevents the development of salt-sensitive hypertension. Hypertension 2014 Feb;63(2):316-23
Date
11/20/2013Pubmed ID
24246383Pubmed Central ID
PMC3947277DOI
10.1161/HYPERTENSIONAHA.113.02041Scopus ID
2-s2.0-84892940481 (requires institutional sign-in at Scopus site) 88 CitationsAbstract
The (pro)renin receptor (PRR), which binds both renin and prorenin, is a newly discovered component of the renin-angiotensin system that is highly expressed in the central nervous system. The significance of brain PRRs in mediating local angiotensin II formation and regulating blood pressure remains unclear. The current study was performed to test the hypothesis that PRR-mediated, nonproteolytic activation of prorenin is the main source of angiotensin II in the brain. Thus, PRR knockout in the brain is expected to prevent angiotensin II formation and development of deoxycorticosterone acetate-salt-induced hypertension. A neuron-specific PRR (ATP6AP2) knockout mouse model was generated using the Cre-LoxP system. Physiological parameters were recorded by telemetry. PRR expression, detected by immunostaining and reverse transcription-polymerase chain reaction, was significantly decreased in the brains of knockout mice compared with wild-type mice. Intracerebroventricular infusion of mouse prorenin increased blood pressure and angiotensin II formation in wild-type mice. This hypertensive response was abolished in PRR-knockout mice in association with a reduction in angiotensin II levels. Deoxycorticosterone acetate-salt increased PRR expression and angiotensin II formation in the brains of wild-type mice, an effect that was attenuated in PRR-knockout mice. PRR knockout in neurons prevented the development of deoxycorticosterone acetate-salt-induced hypertension as well as activation of cardiac and vasomotor sympathetic tone. In conclusion, nonproteolytic activation of prorenin through binding to the PRR mediates angiotensin II formation in the brain. Neuron-specific PRR knockout prevents the development of deoxycorticosterone acetate-salt-induced hypertension, possibly through diminished angiotensin II formation.
Author List
Li W, Peng H, Mehaffey EP, Kimball CD, Grobe JL, van Gool JM, Sullivan MN, Earley S, Danser AH, Ichihara A, Feng YAuthor
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Blood Pressure
Desoxycorticosterone Acetate
Female
Hypertension, Renal
Male
Mice
Mice, Inbred Strains
Mice, Knockout
Mineralocorticoids
Neurons
Proton-Translocating ATPases
Receptors, Cell Surface
Sodium Chloride, Dietary
