Angiotensin II Type 1A Receptors in Vascular Smooth Muscle Cells Do Not Influence Aortic Remodeling in Hypertension
- 1 March 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 57 (3), 577-585
- https://doi.org/10.1161/HYPERTENSIONAHA.110.165274
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 (AT 1 ) receptor promotes vascular pathology in hypertension. To study the role of AT 1 receptors in this process, we generated mice with cell-specific deletion of AT 1 receptors in vascular smooth muscle cells using Cre/Loxp technology. We crossed the SM22 α- Cre transgenic mouse line expressing Cre recombinase in smooth muscle cells with a mouse line bearing a conditional allele of the Agtr1a gene ( Agtr1a flox ), encoding the major murine AT 1 receptor isoform (AT 1A ). In SM22 α- Cre + Agtr1a flox/flox (SMKO) mice, AT 1A 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 AT 1A receptors promote oxidative stress in the aortic wall but are not required for remodeling in angiotensin II–dependent hypertension.Keywords
This publication has 62 references indexed in Scilit:
- Pressure-Induced Renal Injury in Angiotensin II Versus Norepinephrine-Induced Hypertensive RatsHypertension, 2009
- Decreased Nitric Oxide Bioavailability in a Mouse Model of Fabry DiseaseJournal of the American Society of Nephrology, 2009
- The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in miceJCI Insight, 2009
- ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic miceAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritisJCI Insight, 2009
- NADPH oxidases and angiotensin II receptor signalingMolecular and Cellular Endocrinology, 2008
- A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced HypertensionJournal of the American Society of Nephrology, 2008
- An antiproliferative BMP-2/PPARγ/apoE axis in human and murine SMCs and its role in pulmonary hypertensionJCI Insight, 2008
- Is Angiotensin II a Direct Mediator of Left Ventricular Hypertrophy?Hypertension, 2007
- Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidneyProceedings of the National Academy of Sciences of the United States of America, 2006