Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats

Orshal, Julia M.; Khalil, Raouf A.

doi:10.1152/ajpregu.00729.2003

Cited by 77 publications

(58 citation statements)

References 61 publications

(110 reference statements)

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“…28,29 Exogenous IL-6 has been found to impair endotheliumdependent responses to acetylcholine via reductions in NOcyclic GMP signaling. 31 Consistent with this, we found that the impairment of endothelial function in response to Ang II in our study was associated with increases in IL-6 from carotid artery and aorta. Moreover, Ang II reduced eNOS expression in control, but not IL-6 -deficient, mice.…”

Section: Il-6 Deficiency Largely Prevents Ang Ii-induced Endothelial supporting

confidence: 91%

IL-6 Deficiency Protects Against Angiotensin II–Induced Endothelial Dysfunction and Hypertrophy

Schrader

Kinzenbaw

Johnson

et al. 2007

ATVB

166

182

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Objective-The goal of this study was to test the hypothesis that IL-6 mediates the increases in superoxide, vascular hypertrophy, and endothelial dysfunction in response to angiotensin II (Ang II). Methods and Results-Responses of carotid arteries from control and IL-6 -deficient mice were examined after acute (22-hour) incubation with Ang II (10 nmol/L) or chronic infusion of Ang II (1.4 mg/kg/d for 14 days). The hypertrophic response and endothelial dysfunction produced by Ang II infusion was markedly less in carotid arteries from IL-6 -deficient mice than that in control mice. IL-6 deficiency also protected against endothelial dysfunction in response to acute (local) Ang II treatment (eg, 100 mol/L acetylcholine produced 100Ϯ4 and 98Ϯ4% relaxation in vehicle-treated and 51Ϯ4 and 99Ϯ4% relaxation in Ang II-treated, control, and IL-6 -deficient vessels, respectively). Endothelial dysfunction could be reproduced in vessels from IL-6 -deficient mice with combined Ang II plus IL-6 (0.1 nmol/L) treatment. Increases in vascular superoxide and IL-6, as well as reductions in endothelial nitric oxide synthase mRNA expression, produced by Ang II were absent in IL-6 -deficient mice. Conclusions-These data demonstrate that IL-6 is essential for Ang II-induced increases in superoxide, endothelial dysfunction, and vascular hypertrophy. (Arterioscler Thromb Vasc Biol.

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Section: Il-6 Deficiency Largely Prevents Ang Ii-induced Endothelial supporting

confidence: 91%

IL-6 Deficiency Protects Against Angiotensin II–Induced Endothelial Dysfunction and Hypertrophy

Schrader

Kinzenbaw

Johnson

et al. 2007

ATVB

166

182

View full text Add to dashboard Cite

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“…4,[21][22][23] Interestingly, proinflammatory cytokines such as IL-6 have a direct adverse effect on NO-dependent vasorelaxation of experimental aortas. 36 However, it is not possible to define precisely a substance responsible for the changes observed in our study. The positive correlation of PWV and CRP cannot substantiate an etiological role of the latter because trends of these parameters during the study were opposite (Figure 1), and recent data suggest that increase in CRP coincides with the restoration rather than the development of endothelial dysfunction.…”

Section: Aortic Stiffnessmentioning

confidence: 77%

Acute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals

et al. 2005

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Background-Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk.Although an association between inflammatory markers and increased arterial stiffness has been suggested, the causative relationship between inflammation and arterial stiffness has not been investigated. Methods and Results-One hundred healthy individuals were studied according to a randomized, double-blind, sham procedure-controlled design. Each substudy consisted of 2 treatment arms, 1 with Salmonella typhi vaccination and 1 with sham vaccination. Vaccination produced a significant (PϽ0.01) increase in pulse wave velocity (at 8 hours by 0.43 m/s), denoting an increase in aortic stiffness. Wave reflections were reduced significantly (PϽ0.01) by vaccination (decrease in augmentation index of 5.0% at 8 hours and 2.5% at 32 hours) as a result of peripheral vasodilatation. These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein (PϽ0.001), high-sensitivity interleukin-6 (PϽ0.001), and matrix metalloproteinase-9 (PϽ0.01). With aspirin pretreatment (1200 mg PO), neither pulse wave velocity nor augmentation index changed significantly after vaccination (increase of 0.11 m/s and 0.4%, respectively; PϭNS for both). Conclusions-This is the first study to show through a cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections. These findings have important implications, given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties. (Circulation. 2005;112:2193-2200.)

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“…Inflammatory cytokines may contribute to altered ANG II-mediated ROS signaling in the vascular wall after I/R injury. For example, circulating cytokines associated with I/R injury, such as TNF-␣, CRP, and IL-6 induce endothelial oxidative stress (26,30,35,43). Interestingly, Wassmann et al (43) demonstrated that the proinflammatory cytokine IL-6 induced an upregulation of the AT 1 -receptor, thereby facilitating ANG II vasoconstriction and oxidative stress vascular smooth muscle cells an unlikely mechanism in this study given the reduced AT 1b -receptor expression in gracilis arterioles of AKI rats (Table 1).…”

Section: Mechanisms Of Enhanced Ang II Responsivenessmentioning

confidence: 99%

Increased ANG II sensitivity following recovery from acute kidney injury: role of oxidant stress in skeletal muscle resistance arteries

Phillips

Pechman

Leonard

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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DP. Increased ANG II sensitivity following recovery from acute kidney injury: role of oxidant stress in skeletal muscle resistance arteries. Am J Physiol Regul Integr Comp Physiol 298: R1682-R1691, 2010. First published March 24, 2010 doi:10.1152/ajpregu.00448.2009.-Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) results in prolonged impairment of peripheral (i.e., nonrenal) vascular function since skeletal muscle resistance arteries derived from rats 5 wk post-I/R injury, show enhanced responses to ANG II stimulation but not other constrictors. Because vascular superoxide increases ANG II sensitivity, we hypothesized that peripheral responsiveness following recovery from AKI was attributable to vascular oxidant stress. Gracilis arteries (GA) isolated from post-I/R rats (ϳ5 wk recovery) showed significantly greater superoxide levels relative to sham-operated controls, as detected by dihydroeithidium, which was further augmented by acute ANG II stimulation in vitro. Hydrogen peroxide measured by dichlorofluorescein was not affected by ANG II. GA derived from postischemic animals manifested significantly greater constrictor responses in vitro to ANG II than GA from sham-operated controls. The addition of the superoxide scavenging reagent Tempol (10 Ϫ5 M) normalized the response to values similar to sham-operated controls. Apocynin (10 Ϫ6 M) and endothelial denudation nearly abrogated all ANG II-stimulated constrictor activity in GA from post-AKI rats, suggesting an important role for an endothelial-derived source of peripheral oxidative stress. Apocynin treatment in vivo abrogated GA oxidant stress and attenuated ANG II-induced pressor responses post-AKI. Interestingly, gene expression studies in GA vessels indicated a paradoxical reduction in NADPH oxidase subunit and AT1-receptor genes and no effect on several antioxidant genes. Taken together, this study demonstrates that AKI alters peripheral vascular responses by increasing oxidant stress, likely in the endothelium, via an undefined mechanism. ischemia; vascular regulation; oxidant stress ISCHEMIA-REPERFUSION (I/R) of the kidneys in rats is a common model to study the pathogenesis and reversibility of acute kidney injury (AKI). I/R injury results in a profound loss of renal function and significant damage to renal tubular cells. An interesting aspect of this model is the increasingly recognized effects that renal injury has on distant organs. Renal injury is associated with the liberation of a number of cytokines that may result in cardiovascular instability and affect outcome of patients with AKI (11). In animal models, AKI induced by I/R results in immune-mediated damage in the pulmonary system and brain (15,24,27). Similarly, Kelly (23) demonstrated compromised cardiac contractility and cardiac myocyte apoptosis following renal I/R.Despite the typical recovery of renal tubular structure indicative of this model, there are permanent alterations in renal microvascular structure that may promote renal hypoxia and alter renal hemodynamics, there...

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Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats

Cited by 77 publications

References 61 publications

IL-6 Deficiency Protects Against Angiotensin II–Induced Endothelial Dysfunction and Hypertrophy

IL-6 Deficiency Protects Against Angiotensin II–Induced Endothelial Dysfunction and Hypertrophy

Acute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals

Increased ANG II sensitivity following recovery from acute kidney injury: role of oxidant stress in skeletal muscle resistance arteries

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