In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 104, No. 21 ( 2001-11-20), p. 2602-2607
Abstract:
Background Angiotensin II activates 2 distinct G protein–coupled receptors, the AT 1 and AT 2 receptors. Most of the known cardiovascular effects of angiotensin II are mediated by the AT 1 receptor subtype. The aim of the present study was to test whether deletion of the AT 2 receptor gene in mice (AT 2 -KO mice) leads to long-term functional or structural alterations in the cardiovascular system. Methods and Results In vivo pressure responses to angiotensin II or the α 1 -adrenergic receptor agonist phenylephrine were greatly enhanced in AT 2 -KO mice. Deletion of the angiotensin AT 2 receptor did not lead to a compensatory increase of the activity of the circulating renin-angiotensin system, and arterial blood pressure was identical in wild-type control mice (WT) and AT 2 -KO mice. Cardiac contractility as assessed by LV catheterization and by rapid MRI also did not differ between AT 2 -KO and WT mice. Isolated femoral arteries from AT 2 -KO mice, however, showed enhanced vasoconstriction to angiotensin II, norepinephrine, and K + depolarization compared with WT. Morphometric analysis of large and small femoral arteries revealed a significant hypertrophy of media smooth muscle cells. Phospho-P70S6 kinase levels were significantly increased in aortas from AT 2 -KO mice compared with WT mice. Treatment of mice with an ACE inhibitor for 8 weeks abolished the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in AT 2 -KO mice. Conclusions These results indicate that vascular AT 2 receptors inhibit the activity and, hence, hypertrophic signaling by the P70S6 kinase in vivo and thus are important regulators of vascular structure and function.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/hc4601.099401
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
1466401-X
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