0000000000373931
AUTHOR
Mercedes Losada
A critical role for TNFα in the selective attachment of mononuclear leukocytes to angiotensin-II-stimulated arterioles
Abstract Angiotensin II (Ang-II) exerts inflammatory activity and is involved in different cardiovascular disorders. This study has evaluated the involvement of tumor necrosis factor alpha (TNFα) in the leukocyte accumulation elicited by Ang-II. Ang-II (1 nM intraperitoneally in rats) induced TNFα release at 1 hour followed by neutrophil and mononuclear cell recruitment. The administration of an antirat TNFα antiserum had no effect on Ang-IIinduced neutrophil accumulation but inhibited the infiltration of mononuclear cells and reduced CC chemokine content in the peritoneal exudate. Pretreatment with either an anti-TNFα or an anti-IL-4 antiserum decreased Ang-II-induced arteriolar mononuclea…
CXCR2 blockade impairs angiotensin II-induced CC chemokine synthesis and mononuclear leukocyte infiltration.
Objective—Angiotensin II (Ang-II) and mononuclear leukocytes are involved in atherosclerosis. This study reports the inhibition of Ang-II–induced mononuclear cell recruitment by CXCR2 antagonism and the mechanisms involved.Methods and Results—Ang-II (1 nmol/L, i.p. in rats) induced CXC and CC chemokines, followed by neutrophil and mononuclear cell recruitment. Administration of the CXCR2 antagonist, SB-517785-M, inhibited the infiltration of both neutrophils (98%) and mononuclear cells (60%). SB-517785-M had no effect on the increase in CXC chemokine levels but reduced MCP-1, RANTES, and MIP-1α release by 66%, 63%, and 80%, respectively. Intravital microscopy showed that pretreatment with S…
Cigarette smoke-induced pulmonary endothelial dysfunction is partially suppressed by sildenafil.
Abstract Cigarette smoke mediated oxidative stress and endothelial dysfunction are important processes in the pathogenesis of several lung disorders. In this study we evaluated the effect of PDE5 inhibition on pulmonary artery endothelial dysfunction induced by cigarette smoke in vitro . Human pulmonary artery endothelial cells (HPAEC) were incubated in the absence or presence of PDE5 inhibitor sildenafil (10 nM–1 μM), PKG agonist 8-Br-cGMP (1 mM), or the antioxidants dyphenyleneiodonium (DPI 1 μM) and N -acetylcysteine (NAC 1 mM) for 30 min. Then, cigarette smoke extract (CSE) was added for 24 h. CSE (2.5–10%)-induced ROS generation was suppressed by DPI, and partially reversed by sildenaf…
Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo.
AbstractAngiotensin-II (Ang-II) has inflammatory activity and is involved in different diseases associated with the cardiovascular system. This study has evaluated the effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us, secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant neutrophil accumulation, which was maximal at 4–8 h. BM inhibited neutrophil infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%, respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM inhibited the release of cytokine-inducible neutrophil chemoattractant/ke…