Angiotensin II-induced vascular dysfunction is mediated by the AT1A receptor in mice

Michael J RYAN; Sean P DIDION; Satya MATHUR; Frank M FARACI; Curt D SIGMUND

doi:10.1161/01.HYP.0000123074.89717.3d

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Angiotensin II-induced vascular dysfunction is mediated by the AT1A receptor in mice

Journal article

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Angiotensin II-induced vascular dysfunction is mediated by the AT1A receptor in mice

Michael J RYAN, Sean P DIDION, Satya MATHUR, Frank M FARACI and Curt D SIGMUND

Hypertension (Dallas, Tex. 1979), Vol.43(5), pp.1074-1079

2004

DOI: 10.1161/01.HYP.0000123074.89717.3d

PMID: 15007032

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Abstract

Many of the actions of angiotensin II (Ang II) are mediated by angiotensin type 1 receptors (AT1), of which there are 2 pharmacologically indistinguishable subtypes (AT1A and AT1B). The purpose of this study was to evaluate the effect of an AT1A homozygous deletion (AT1A-/-) on vascular reactivity. AT1A-/- mice and control littermates (AT1A+/+) were infused with vehicle (saline) or Ang II (1000 ng x kg(-1) x min(-1)) for 7 days by osmotic pumps. Systolic pressure was increased in AT1A+/+ mice (Delta45+/-8 mm Hg, P<0.0001) but unchanged in AT1A-/- mice (Delta5+/-3 mm Hg, P>0.13) on day 7. The carotid artery response to the vasodilators acetylcholine (ACh), nitroprusside, and papaverine and to the vasoconstrictors phenylephrine, U46619, 5-hydroxytryptamine (5-HT), and KCl were not different between vehicle-infused AT1A+/+ and AT1A-/- animals. Carotid relaxation to ACh was impaired and contraction to 5-HT was increased in Ang II-infused AT1A+/+ mice. Ang II did not affect carotid responses in AT1A-/- mice. Superoxide, measured by lucigenin (5 micromol/L), and hydroethidine staining were not different between AT1A+/+ and AT1A-/- mice after vehicle or Ang II infusion, suggesting that it was not contributing to the altered ACh and 5-HT responses. The Rho-kinase inhibitor Y-27632 (1 micromol/L) attenuated the 5-HT response in both vehicle- and Ang II-infused AT1A+/+ mice. Moreover, concentration-dependent relaxation to Y-27632 and RhoA protein expression were not different in vehicle- or Ang II-infused AT1A+/+. These data demonstrate that the AT1A receptor is required for Ang II-induced changes in carotid artery function.

Fundamental and applied biological sciences. Psychology

Cardiology. Vascular system

Arterial hypertension. Arterial hypotension

Blood vessels and receptors

Biological and medical sciences

Medical sciences

Clinical manifestations. Epidemiology. Investigative techniques. Etiology

Vertebrates: cardiovascular system

Blood and lymphatic vessels

Details

Title: Subtitle: Angiotensin II-induced vascular dysfunction is mediated by the AT1A receptor in mice
Creators: Michael J RYAN - Department of Internal Medicine, Cardiovascular Center, Roy J. and Lucille A. Carver College of Medicine. University of Iowa, Iowa City, United States
Sean P DIDION - Department of Internal Medicine, Cardiovascular Center, Roy J. and Lucille A. Carver College of Medicine. University of Iowa, Iowa City, United States
Satya MATHUR - Department of Internal Medicine, Cardiovascular Center, Roy J. and Lucille A. Carver College of Medicine. University of Iowa, Iowa City, United States
Frank M FARACI - Department of Internal Medicine, Cardiovascular Center, Roy J. and Lucille A. Carver College of Medicine. University of Iowa, Iowa City, United States
Curt D SIGMUND - Department of Internal Medicine, Cardiovascular Center, Roy J. and Lucille A. Carver College of Medicine. University of Iowa, Iowa City, United States
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.43(5), pp.1074-1079
DOI: 10.1161/01.HYP.0000123074.89717.3d
PMID: 15007032
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Publisher: Lippincott; Philadelphia, PA; Hagerstown, MD
Language: English
Date published: 2004
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040548402771

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