Journal article
Impaired Endothelial Function in Transgenic Mice Expressing Both Human Renin and Human Angiotensinogen
Stroke (1970), Vol.31(3), pp.760-765
03/2000
DOI: 10.1161/01.STR.31.3.760
PMID: 10700516
Abstract
Background and purpose: Chronic hypertension is a risk factor for carotid vascular disease and stroke. Mechanisms that account for alterations in carotid and cerebral vascular function during hypertension are poorly defined and based almost exclusively on studies in the spontaneously hypertensive rat, a model in which hypertension has an unknown etiology and in which the genetic background is dissimilar to the most commonly used normotensive control, the Wistar-Kyoto rat.
Methods: In this study we examined vascular function in a defined model of hypertension, double transgenic mice that overexpress both human renin (R+) and human angiotensinogen (A+). We studied vessels in vitro from R+/A+ mice as well as nontransgenic (R-/A-) and single transgenic (R-/A+ or R+/A-) littermate controls.
Results: After submaximal precontraction with U46619 or prostaglandin F(2alpha), acetylcholine, which produces relaxation mediated by endothelial nitric oxide synthase, produced marked relaxation of carotid arteries in control mice but was impaired in R+/A+ mice. For example, 1 micromol/L acetylcholine relaxed the carotid artery by 79+/-4% versus 44+/-7% (P<0.01) in control and R+/A+ mice, respectively. Impaired responses to acetylcholine in R+/A+ mice could be restored toward normal with indomethacin (10 micromol/L). In contrast, relaxation of the carotid artery in response to nitroprusside and papaverine was similar in R+/A+ mice and control mice.
Conclusions: These findings indicate that acetylcholine-induced relaxation of carotid artery is impaired selectively in mice made hypertensive by expression of human renin and human angiotensinogen. The mechanism of this impairment may involve production of a cyclooxygenase-derived contracting factor.
Details
- Title: Subtitle
- Impaired Endothelial Function in Transgenic Mice Expressing Both Human Renin and Human Angiotensinogen
- Creators
- Sean P Didion - From the Departments of Internal Medicine (S.P.D., C.D.S., F.M.F.), Pharmacology (F.M.F.), and Physiology (C.D.S.), Cardiovascular Center, University of Iowa College of Medicine, Iowa CityCurt D Sigmund - From the Departments of Internal Medicine (S.P.D., C.D.S., F.M.F.), Pharmacology (F.M.F.), and Physiology (C.D.S.), Cardiovascular Center, University of Iowa College of Medicine, Iowa CityFrank M Faraci - From the Departments of Internal Medicine (S.P.D., C.D.S., F.M.F.), Pharmacology (F.M.F.), and Physiology (C.D.S.), Cardiovascular Center, University of Iowa College of Medicine, Iowa City
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.31(3), pp.760-765
- DOI
- 10.1161/01.STR.31.3.760
- PMID
- 10700516
- NLM abbreviation
- Stroke
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 03/2000
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040598602771
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