Leukocyte-dependent responses of the microvasculature to chronic angiotensin II Exposure

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Abstract

Angiotensin II (Ang II) contributes to the pathogenesis of hypertension and other cardiovascular diseases. Ang II induces a pro-oxidative, proinflammatory, and prothrombogenic phenotype in vascular endothelial cells. Although the peptide promotes the recruitment of leukocytes and platelets and induces oxidative stress in the microvasculature, it remains unclear whether and how the blood cell recruitment is linked to the production of reactive oxygen species. In this study, we addressed the contributions of Ang II type 1 receptors (AT1r) and gp91phox to the recruitment of leukocytes and platelets and reactive oxygen species production in venules during chronic (2-week) infusion of Ang II in wild-type (WT) and mutant mice. Intravital video microscopy was used to measure the adhesion and emigration of leukocytes, the adhesion of fluorescently labeled platelets, and dihydrorhodamine oxidation (a measure of oxidative stress) in cremaster muscle postcapillary venules. In WT mice, Ang II infusion induced a time-dependent increase in the adhesion of leukocytes and platelets and enhanced reactive oxygen species production in venules. These changes in blood cell adhesion and reactive oxygen species production were not observed in AT1r-/- mice, AT 1r-/- bone marrow chimeras (blood cells deficient in AT1r), gp91phox-/- mice, gp91phox-/- chimeras (blood cells or endothelial cells deficient in gp91phox), and in WT mice rendered granulocytopenic via intraperitoneal injection of antimouse granulocyte receptor 1 antibody. Thrombocytopenic WT mice (platelets depleted by intraperitoneal injection of rabbit antimouse thrombocyte antiserum) responded similar to WT mice. These findings implicate leukocyte-associated AT 1r and gp91phox in the induction of the pro-oxidative, proinflammatory, and prothrombogenic phenotype assumed by microvessels that is chronically exposed to elevated Ang II. © 2012 American Heart Association, Inc.

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Yildirim, A., Russell, J., Yan, L. S. S., Senchenkova, E. Y., & Granger, D. N. (2012). Leukocyte-dependent responses of the microvasculature to chronic angiotensin II Exposure. Hypertension, 60(6), 1503–1509. https://doi.org/10.1161/HYPERTENSIONAHA.112.198465

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