Angiotensin II-induced vascular dysfunction is mediated by the AT1A receptor in mice. Hypertension 2004 May;43(5):1074-9
Date
03/10/2004Pubmed ID
15007032DOI
10.1161/01.HYP.0000123074.89717.3dScopus ID
2-s2.0-2342586810 (requires institutional sign-in at Scopus site) 74 CitationsAbstract
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 CDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAcetylcholine
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