Differential Effects of Short-Term Ace- And At1-Receptor Inhibition on Postischemic Injury and Leukocyte Adherence in Vivo and in Vitro

Guba, Markus; Steinbauer, Markus; Buchner, Markus; Frölich, Daniela; Farkas, Sándor; Kw, Jauch; Anthuber, Matthias

doi:10.1097/00024382-200003000-00004

Cited by 44 publications

(23 citation statements)

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“…75 Experimental evidence indicates the inhibition of angiotensin-converting enzyme, resulting in impeded adherence of polymorphonuclear cells to the endothelium and in diminished intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. 76 This work presents a new picture of neutrophils as circulating cells that are highly sensitive to Ang II, and it provides novel evidence to support the view that essential hypertension is a generalized type of membranopathy in which vascular contractile cells are not the only cell type involved. 77 Figure 10.…”

Section: Discussionmentioning

confidence: 66%

Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB

Bekay

Álvarez

Monteseirı́n

et al. 2003

Blood

156

141

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Neutrophils are mobilized to the vascular wall during vessel inflammation. Published data are conflicting on phagocytic nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activation during the hypertensive state, and the capacity of angiotensin II (Ang II) to modulate the intracellular redox status has not been analyzed in neutrophils. We here describe that Ang II highly stimulates endogenous and extracellular O 2 ؊ production in these cells, consistent with the translocation to the cell membrane of the cytosolic components of NADPH oxidase, p47 phox , and p67 phox . The Ang II-dependent O 2 ؊ production was suppressed by specific inhibitors of AT1 receptors, of the p38MAPK and ERK1/2 pathways, and of flavin oxidases. Furthermore, Ang II induced a robust phosphorylation of p38MAPK, ERK1/2, and JNK1/2 (particularly JNK2), which was hindered by inhibitors of NADPH oxidase, tyrosine kinases, and ROS scavengers. Ang II increased cytosolic Ca 2؉ levels-released mainly from calcium stores-enhanced the syn- IntroductionAngiotensin II (Ang II), the main peptide hormone of the reninangiotensin system, induces leukocyte recruitment to the vessel wall, which constitutes a hallmark of the early stages of atherosclerosis and several hypertensive diseases. 1 In addition, it plays a regulatory role on blood pressure and circulation volume and on the proliferation of vascular smooth muscle cells. 2 Ang II acts through high-affinity cell surface receptors (AT1), which are linked to pathways classically associated with G-protein-coupled and tyrosine-kinase-mediated responses. 3 Although most studies on Ang II have been carried out in smooth muscle and endothelial cells, experimental evidence has been obtained on its effects on circulating cells. AT1 receptors for Ang II have been found recently in circulating neutrophils 4 and human peripheral monocytes, 5 and Ang II-induced cell activation in the latter has been reported. 6 In this context, the migration of leukocytes from blood to sites of inflammation and their adhesion to endothelial cells are primary events taking place during the acute inflammatory response and the pathogenesis of vascular diseases. 7 Because chronic inflammation of vessel walls is a hallmark of atherosclerosis, 8 and reactive oxygen species (ROS) such as superoxide anion (O 2 Ϫ ) and H 2 O 2 constitute the main intermediary molecules responsible for inflammation, 9 a link between atherosclerosis and ROS production has been postulated. 10 Nicotinamideadenine dinucleotide phosphate (NADPH) oxidase of phagocytes catalyzes the reduction of oxygen to O 2 Ϫ . In resting cells this enzyme is inactive, and its components are distributed between the cytosol and the membrane of secretory vesicles. When phagocytic cells are activated, the enzyme's cytosolic components associate to membrane-bound components and assemble into catalytically active NADPH oxidase. 11 It has been reported that Ang II-induced hypertrophy of vascular smooth muscle cells is mediated by both O 2 Ϫ and H 2 O 2 . 12 In addition, ROS ha...

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Section: Discussionmentioning

confidence: 66%

Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB

Bekay

Álvarez

Monteseirı́n

et al. 2003

Blood

156

141

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“…An elegant study comparing the effects of the ACEi enalapril and the ARB losartan evaluating in vivo and in vitro data on cell injury and temporal association of leukocyte endothelial interaction in response to ischemia-reperfusion date 2000 [218]. The extent and temporal correlation of cellular damage (propidium-iodide staining), microvascular perfusion failure and leukocyte-endothelial interaction (leukocyte adherence) were investigated by means of intravital microscopy, after the application of hemodynamically ineffective doses of enalapril and losartan (5 mg/kg).…”

Section: Part IV -Anti-inflammatory Effects Of Ace-imentioning

confidence: 99%

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Raimondo¹,

Tuttolomondo²,

Buttà³

et al. 2012

CPD

105

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Abstract:The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosteron system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Recpetor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEi's reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflmmatory effect of drugs bocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.

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“…Thus, it has been shown that enalapril (5 mg/kg) reduced the adherence of PMNs [15] , verapamil (10 -4 mol/l) inhibited leukocyte functions [16] , and ranitidin (30 mg/kg, i.v.) inhibited the release of elastase as well as the production of O 2 in PMNs [17] .…”

Section: Discussionmentioning

confidence: 99%

Comparison of Polymorphonuclear Leukocyte Functions in Elderly Patients and Healthy Young Volunteers

Göçer

Gürer²,

Erten³

et al. 2005

Med Princ Pract

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Objective: To compare the polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing activity) of elderly patients with healthy young volunteers. Subjects and Methods: Fifty-nine elderly patients who had various diseases (cancer, hypertension and diabetes mellitus, DM) and 10 healthy young volunteers were included in this study. Ficoll-Hypaque gradient centrifugation was used to isolate PMNs from venous blood containing EDTA (0.1 g/ml). Phagocytosis and intracellular killing activity of neutrophils were assayed using a modification of Alexander’s method, in which serum opsonins, number of neutrophils and number of microorganisms are standardized in order to detect both increases and decreases in phagocytosis and intracellular killing as well as combined abnormalities of these two functions. The least significant difference test was used to compare the results in the two groups. Results: Phagocytic activity of PMNs from patients with cancer was significantly higher than that of healthy young volunteers (p < 0.05) and elderly patients with hypertension and DM (p < 0.05). There was no statistical difference between the phagocytic activity of PMNs from elderly patients with hypertension and DM and healthy young volunteers (p > 0.05). The intracellular killing activity of PMNs from elderly patients with hypertension, DM and cancer was significantly lower than that of healthy young volunteers (p = 0.001, p < 0.0001, p = 0.003, respectively). Conclusions: The intracellular killing activity of PMNs from elderly patients was significantly decreased when compared with that of healthy young volunteers. Ageing, chronic diseases and drugs used in the treatment of these elderly patients may be the cause for decreased intracellular killing activity.

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Differential Effects of Short-Term Ace- And At1-Receptor Inhibition on Postischemic Injury and Leukocyte Adherence in Vivo and in Vitro

Cited by 44 publications

References 0 publications

Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB

Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Comparison of Polymorphonuclear Leukocyte Functions in Elderly Patients and Healthy Young Volunteers

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