2000
DOI: 10.1161/01.cir.102.17.2118
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Angiotensin II Induces Leukocyte–Endothelial Cell Interactions In Vivo Via AT 1 and AT 2 Receptor–Mediated P-Selectin Upregulation

Abstract: Background-Angiotensin II (Ang II) plays a critical role in the development of vascular lesions in hypertension, atherosclerosis, and several renal diseases. Because Ang II may contribute to the leukocyte recruitment associated with these pathological states, the aim of the present study was to assess the role of Ang II in leukocyte-endothelial cell interactions in vivo. Methods and Results-Intravital microscopy of the rat mesenteric postcapillary venules was used. Sixty minutes of superfusion with 1 nmol/L An… Show more

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Cited by 145 publications
(148 citation statements)
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“…23 Like IL-8, P-selectin is presynthesized and stored in endothelial cell Weibel-Palade bodies 14 and is rapidly mobilized to the cell surface after exposure to Ang II. 15 Because CXC chemokines induce P-selectin upregulation, 24 it is possible that the release of IL-8 in response to Ang II augments the P-selectin upregulation. Therefore, in addition to their role in Ang II-induced neutrophil adhesion and migration, CXC chemokines may also contribute to the rolling response elicited by this peptide hormone.…”
Section: Discussionmentioning
confidence: 99%
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“…23 Like IL-8, P-selectin is presynthesized and stored in endothelial cell Weibel-Palade bodies 14 and is rapidly mobilized to the cell surface after exposure to Ang II. 15 Because CXC chemokines induce P-selectin upregulation, 24 it is possible that the release of IL-8 in response to Ang II augments the P-selectin upregulation. Therefore, in addition to their role in Ang II-induced neutrophil adhesion and migration, CXC chemokines may also contribute to the rolling response elicited by this peptide hormone.…”
Section: Discussionmentioning
confidence: 99%
“…15 In brief, male Sprague-Dawley rats (body weight, 200 to 250 g) were anesthetized with sodium pentobarbital (65 mg/kg IP). A segment of the midjejunum was exteriorized and placed over an optically clear viewing pedestal maintained at 37°C.…”
Section: Intravital Microscopymentioning
confidence: 99%
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“…ANG II can stimulate the release of other vasoactive and proinflammatory cytokines (35). ANG II increased leukocyte rolling, adhesion, and migration in rat mesenteric postcapillary venules (1,29). Involvement of nuclear factor-B, p38 mitogen-activated protein kinase (MAP) kinase, and production of reactive oxygen species has been attributed to the proinflammatory role of ANG II (8).…”
mentioning
confidence: 99%
“…In addition, we have recently found that cyclic AMP elevating agents which activate adenylate cyclase such as forskolin, salbutamol and iloprost as well as the nonspeci®c PDE inhibitor, theophylline, or the selective PDE-4 inhibitor, rolipram, are potent inhibitors of angiotensin II-induced leukocyte endothelial cell interactions in vivo regardless of the mechanism employed to elevate cyclic AMP levels (Alvarez et al, 2001b). The eects observed seemed to be mediated through endothelial P-selectin downregulation, since angiotensin-II-induced leukocyte recruitment is primarily dependent on increased endothelial P-selectin expression (Piqueras et al, 2000). Nevertheless, although the inhibition of P-selectin expression may delay the onset of leukocyte adhesion and emigration, a direct eect of rolipram on leukocyte surface adhesion molecule expression cannot be excluded, since downregulation of b 2 -integrins by this PDE-4 inhibitor has been extensively demonstrated in several in vitro studies (Derian et al, 1995;Teixeira et al, 1996;Berends et al, 1997;Santamaria et al, 1997).…”
Section: Discussionmentioning
confidence: 99%