Journal article
The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes
Circulation research, Vol.83(10), pp.1047-1058
11/16/1998
DOI: 10.1161/01.RES.83.10.1047
PMID: 9815152
Abstract
Abstract —We have previously shown that mice transgenic for both the human renin and human angiotensinogen genes (RA+) exhibit appropriate tissue- and cell-specific expression of both transgenes, have 4-fold higher plasma angiotensin II (AII) levels, and are chronically hypertensive. However, the relative contribution of circulating and tissue-derived AII in causing hypertension in these animals is not known. We hypothesized that the brain renin-angiotensin system contributes to the elevated blood pressure in this model. To address this hypothesis, mean arterial pressure (MAP) and heart rate were measured in conscious, unrestrained mice after they were instrumented with intracerebroventricular cannulae and carotid arterial and jugular vein catheters. Intracerebroventricular administration of the selective AII type 1 (AT-1) receptor antagonist losartan (10 μg, 1 μL) caused a significantly greater peak fall in MAP in RA+ mice than in nontransgenic RA− controls (−29±4 versus −4±2 mm Hg, P <0.01). To explore the mechanism of a central renin-angiotensin system–dependent hypertension in RA+ mice, we determined the relative depressor responses to intravenous administration of the ganglionic blocking agent hexamethonium (5 mg/kg) or an arginine vasopressin (AVP) V 1 receptor antagonist (AVPX, 10 μg/kg). Hexamethonium caused equal lowering of MAP in RA+ mice and controls (−46±3 versus −52±3, P >0.05), whereas AVPX caused a significantly greater fall in MAP in RA+ compared with RA− mice (−24±2 versus −6±1, P <0.01). Consistent with this was the observation that circulating AVP was 3-fold higher in RA+ mice than in control mice. These results suggest that increased activation of central AT-1 receptors, perhaps those located at sites involved in AVP release from the posterior pituitary gland, plays a role in the hypertension in RA+ mice. Furthermore, our finding that both human transgenes are expressed in brain regions of RA+ mice known to be involved in cardiovascular regulation raises the possibility that augmented local production of AII and increased activation of AT-1 receptors at these sites is involved.
Details
- Title: Subtitle
- The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes
- Creators
- Robin L Davisson - From the Departments of Internal Medicine and Physiology & Biophysics (R.L.D., C.D.S.), Department of Anatomy and Cell Biology (G.Y., M.D.C.), and Department of Psychology (T.G.B., A.K.J.), The University of Iowa College of Medicine, Iowa City, IowaGongyu Yang - From the Departments of Internal Medicine and Physiology & Biophysics (R.L.D., C.D.S.), Department of Anatomy and Cell Biology (G.Y., M.D.C.), and Department of Psychology (T.G.B., A.K.J.), The University of Iowa College of Medicine, Iowa City, IowaTerry G Beltz - From the Departments of Internal Medicine and Physiology & Biophysics (R.L.D., C.D.S.), Department of Anatomy and Cell Biology (G.Y., M.D.C.), and Department of Psychology (T.G.B., A.K.J.), The University of Iowa College of Medicine, Iowa City, IowaMartin D Cassell - From the Departments of Internal Medicine and Physiology & Biophysics (R.L.D., C.D.S.), Department of Anatomy and Cell Biology (G.Y., M.D.C.), and Department of Psychology (T.G.B., A.K.J.), The University of Iowa College of Medicine, Iowa City, IowaAlan Kim Johnson - From the Departments of Internal Medicine and Physiology & Biophysics (R.L.D., C.D.S.), Department of Anatomy and Cell Biology (G.Y., M.D.C.), and Department of Psychology (T.G.B., A.K.J.), The University of Iowa College of Medicine, Iowa City, IowaCurt D Sigmund - From the Departments of Internal Medicine and Physiology & Biophysics (R.L.D., C.D.S.), Department of Anatomy and Cell Biology (G.Y., M.D.C.), and Department of Psychology (T.G.B., A.K.J.), The University of Iowa College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.83(10), pp.1047-1058
- DOI
- 10.1161/01.RES.83.10.1047
- PMID
- 9815152
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 11/16/1998
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Psychological and Brain Sciences; Neuroscience and Pharmacology; Health, Sport, and Human Physiology
- Record Identifier
- 9984213409002771
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