Faculty Collaboration Database

Angiotensin II-induced vascular dysfunction is mediated by the AT1A receptor in mice. Hypertension 2004 May;43(5):1074-9

Date

03/10/2004

Pubmed ID

15007032

DOI

10.1161/01.HYP.0000123074.89717.3d

Scopus ID

2-s2.0-2342586810 (requires institutional sign-in at Scopus site)   71 Citations

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.

Author List

Ryan MJ, Didion SP, Mathur S, Faraci FM, Sigmund CD

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Acetylcholine
Amides
Angiotensin II
Animals
Aorta
Carotid Arteries
Infusion Pumps, Implantable
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide
Nitroprusside
Papaverine
Phenylephrine
Potassium Chloride
Pyridines
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Reverse Transcriptase Polymerase Chain Reaction
Sequence Deletion
Serotonin
Superoxides
Vasoconstriction
Vasoconstrictor Agents
Vasodilator Agents
rhoA GTP-Binding Protein