Central and peripheral mechanisms of T-Lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension

Marvar, P.J., Thabet, S.R., Guzik, T.J., Lob, H.E., McCann, L.A., Weyand, C., Gordon, F.J. and Harrison, D.G. (2010) Central and peripheral mechanisms of T-Lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circulation Research, 107(2), pp. 263-270. (doi: 10.1161/CIRCRESAHA.110.217299) (PMID:20558826) (PMCID:PMC2921936)

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Abstract

<p>Rationale: We have previously found that T lymphocytes are essential for development of angiotensin II–induced hypertension; however, the mechanisms responsible for T-cell activation in hypertension remain undefined.</p> <p>Objective: We sought to study the roles of the CNS and pressure elevation in T-cell activation and vascular inflammation caused by angiotensin II.</p> <p>Methods and Results: To prevent the central actions of angiotensin II, we created anteroventral third cerebral ventricle (AV3V) lesions in mice. The elevation in blood pressure in response to angiotensin II was virtually eliminated by AV3V lesions, as was activation of circulating T cells and the vascular infiltration of leukocytes. In contrast, AV3V lesioning did not prevent the hypertension and T-cell activation caused by the peripheral acting agonist norepinephrine. To determine whether T-cell activation and vascular inflammation are attributable to central influences or are mediated by blood pressure elevation, we administered hydralazine (250 mg/L) in the drinking water. Hydralazine prevented the hypertension and abrogated the increase in circulating activated T cells and vascular infiltration of leukocytes caused by angiotensin II.</p> <p>Conclusions: We conclude that the central and pressor effects of angiotensin II are critical for T-cell activation and development of vascular inflammation. These findings also support a feed-forward mechanism in which modest degrees of blood pressure elevation lead to T-cell activation, which in turn promotes inflammation and further raises blood pressure, leading to severe hypertension.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Guzik, Professor Tomasz
Authors: Marvar, P.J., Thabet, S.R., Guzik, T.J., Lob, H.E., McCann, L.A., Weyand, C., Gordon, F.J., and Harrison, D.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation Research
ISSN:0009-7330
ISSN (Online):1524-4571

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