Angiotensin II type 1A receptors in vascular smooth muscle cells do not influence aortic remodeling in hypertension

Matthew A. Sparks, Kelly K. Parsons, Johannes Stegbauer, Susan Gurley, Anuradha Vivekanandan-Giri, Christopher N. Fortner, Jay Snouwaert, Eric W. Raasch, Robert C. Griffiths, Timothy A.J. Haystead, Thu H. Le, Subramaniam Pennathur, Beverly Koller, Thomas M. Coffman

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Vascular injury and remodeling are common pathological sequelae of hypertension. Previous studies have suggested that the renin-angiotensin system acting through the type 1 angiotensin II (AT1) receptor promotes vascular pathology in hypertension. To study the role of AT1 receptors in this process, we generated mice with cell-specific deletion of AT1 receptors in vascular smooth muscle cells using Cre/Loxp technology. We crossed the SM22α-Cre transgenic mouse line expressing Cre recombinase in smooth muscle cells with a mouse line bearing a conditional allele of the Agtr1a gene (Agtr1a), encoding the major murine AT1 receptor isoform (AT1A). In SM22α-CreAgtr1a (SMKO) mice, AT1A receptors were efficiently deleted from vascular smooth muscle cells in larger vessels but not from resistance vessels such as preglomerular arterioles. Thus, vasoconstrictor responses to angiotensin II were preserved in SMKO mice. To induce hypertensive vascular remodeling, mice were continuously infused with angiotensin II for 4 weeks. During infusion of angiotensin II, blood pressures increased significantly and to a similar extent in SMKO and control mice. In control mice, there was evidence of vascular oxidative stress indicated by enhanced nitrated tyrosine residues in segments of aorta; this was significantly attenuated in SMKO mice. Despite these differences in oxidative stress, the extent of aortic medial expansion induced by angiotensin II infusion was virtually identical in both groups. Thus, vascular AT1A receptors promote oxidative stress in the aortic wall but are not required for remodeling in angiotensin II-dependent hypertension.

Original languageEnglish (US)
Pages (from-to)577-585
Number of pages9
JournalHypertension
Volume57
Issue number3 PART 2
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

Angiotensin Type 1 Receptor
Vascular Smooth Muscle
Smooth Muscle Myocytes
Hypertension
Angiotensin II
Blood Vessels
Oxidative Stress
Angiotensin Receptors
Vascular System Injuries
Arterioles
Vasoconstrictor Agents
Renin-Angiotensin System
Transgenic Mice
Tyrosine
Aorta
Protein Isoforms
Alleles
Pathology
Blood Pressure
Technology

Keywords

  • angiotensin II
  • aorta
  • hyperplasia
  • hypertension
  • hypertrophy
  • smooth muscle

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Sparks, M. A., Parsons, K. K., Stegbauer, J., Gurley, S., Vivekanandan-Giri, A., Fortner, C. N., ... Coffman, T. M. (2011). Angiotensin II type 1A receptors in vascular smooth muscle cells do not influence aortic remodeling in hypertension. Hypertension, 57(3 PART 2), 577-585. https://doi.org/10.1161/HYPERTENSIONAHA.110.165274

Angiotensin II type 1A receptors in vascular smooth muscle cells do not influence aortic remodeling in hypertension. / Sparks, Matthew A.; Parsons, Kelly K.; Stegbauer, Johannes; Gurley, Susan; Vivekanandan-Giri, Anuradha; Fortner, Christopher N.; Snouwaert, Jay; Raasch, Eric W.; Griffiths, Robert C.; Haystead, Timothy A.J.; Le, Thu H.; Pennathur, Subramaniam; Koller, Beverly; Coffman, Thomas M.

In: Hypertension, Vol. 57, No. 3 PART 2, 01.03.2011, p. 577-585.

Research output: Contribution to journalArticle

Sparks, MA, Parsons, KK, Stegbauer, J, Gurley, S, Vivekanandan-Giri, A, Fortner, CN, Snouwaert, J, Raasch, EW, Griffiths, RC, Haystead, TAJ, Le, TH, Pennathur, S, Koller, B & Coffman, TM 2011, 'Angiotensin II type 1A receptors in vascular smooth muscle cells do not influence aortic remodeling in hypertension', Hypertension, vol. 57, no. 3 PART 2, pp. 577-585. https://doi.org/10.1161/HYPERTENSIONAHA.110.165274
Sparks, Matthew A. ; Parsons, Kelly K. ; Stegbauer, Johannes ; Gurley, Susan ; Vivekanandan-Giri, Anuradha ; Fortner, Christopher N. ; Snouwaert, Jay ; Raasch, Eric W. ; Griffiths, Robert C. ; Haystead, Timothy A.J. ; Le, Thu H. ; Pennathur, Subramaniam ; Koller, Beverly ; Coffman, Thomas M. / Angiotensin II type 1A receptors in vascular smooth muscle cells do not influence aortic remodeling in hypertension. In: Hypertension. 2011 ; Vol. 57, No. 3 PART 2. pp. 577-585.
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