Oxidized Low-Density Lipoprotein Enhances Myogenic Tone in the Rabbit Posterior Cerebral Artery Through the Release of Endothelin-1

Xie, Hua; Bevan, John A.

doi:10.1161/01.str.30.11.2423

Cited by 19 publications

(10 citation statements)

References 54 publications

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“…Moreover, we found an increased vascular ET A expression in tumor arterioles, which is also very likely to contribute to the observed myogenic tone. Exaggerated production of ET-1 has been reported previously to mediate similar increase in myogenic constriction in cerebral arteries exposed to oxidized low-density lipoprotein (40) and arterioles isolated from hypertensive rats (41). Together with our study, these reports indicate that pathological states such as atherosclerosis, hypertension, and tumor growth can transform vessels devoid of myogenic tone in vessels prone to blood flow autoregulation.…”

Section: Discussionsupporting

confidence: 91%

Endothelin-1 Is a Critical Mediator of Myogenic Tone in Tumor Arterioles

Sonveaux¹,

Dessy²,

Martinive³

et al. 2004

Cancer Research

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Although derived from the host tissue, the tumor vasculature is under the influence of the tumor microenvironment and needs to adapt to the resistance to blood flow inherent to the dynamics of tumor growth. Such vascular remodeling can offer selective targets to pharmacologically modulate tumor perfusion and thereby improve the efficacy of conventional anticancer treatments. Radiotherapy and chemotherapy can, indeed, take advantage of a better tumor oxygenation and drug delivery, respectively, both partly dependent on the tumor blood supply.Here, we showed that isolated tumor arterioles mounted in a pressure myograph have the ability, contrary to size-matched healthy arterioles, to contract in response to a transluminal pressure increase. This myogenic tone was exquisitely dependent on the endothelin-1 pathway because it was completely abolished by the selective endothelin receptor A (ET A ) antagonist BQ123. This selectivity was additionally supported by the large increase in endothelin-1 abundance in tumors and the higher density of the ET A receptors in tumor vessels. We also documented by using laser Doppler microprobes and imaging that administration of the ET A antagonist led to a significant increase in tumor blood flow, whereas the perfusion in control healthy tissue was not altered. Finally, we provided evidence that acute administration of the ET A antagonist could significantly stimulate tumor oxygenation, as determined by electron paramagnetic resonance oximetry, and increase the efficacy of low-dose, clinically relevant fractionated radiotherapy.Thus, blocking the tumor-selective increase in the vascular endothelin-1/ ET A pathway led us to unravel an important reserve of vasorelaxation that can be exploited to selectively increase tumor response to radiotherapy.

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Section: Discussionsupporting

confidence: 91%

Endothelin-1 Is a Critical Mediator of Myogenic Tone in Tumor Arterioles

Sonveaux¹,

Dessy²,

Martinive³

et al. 2004

Cancer Research

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“…In this respect, NSC MS facilitation might have implications in terms of increased myogenic response by ET-1 [10,13,28]. Since the inner diameter of the patch pipette was around 1 μm, when stretched by −15 mm Hg of pressure, a hemispheric plasma membrane in the pipette tip would be under the tension of 20 dyn/cm or higher depending on the geometry of a patch membrane.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the direct vasoconstrictive effects, ET-1 also enhances myogenic vascular tone [10,13,[27][28][29]. Because NSC MS may play a critical role in myogenic autoregulation, it might be expected that NSC MS are activated by ET-1.…”

Section: Introductionmentioning

confidence: 99%

Mechanosensitive nonselective cation channel facilitation by endothelin-1 is regulated by protein kinase C in arterial myocytes

Lee

Baek

Park³

et al. 2007

Cardiovascular Research

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Objective: The mechanosensitive nonselective cation channel (NSC MS ) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC MS and on the myogenic response of arteries. Methods: Cell-attached patch-clamp techniques were applied to rabbit pulmonary and cerebral arterial smooth muscle cells using a 140 mM CsCl pipette and bath solutions (Ca 2+ -free, 1 mM EGTA). Myogenic responses were determined by video analysis of pressurized arteries. Results: The application of negative pressures through the pipette activated NSC MS , and this was augmented by bath application of ET-1 (1 pM-30 nM). ET-1 lowered the lowest pressure required for NSC MS activation. NSC MS facilitation by ET-1 was prevented by BQ-123 (1 μM, an ET A antagonist) but not by BQ-788 (1 μM, an ET B antagonist). Phorbol 12-myristate 13-acetate (PMA, 100 nM), a protein kinase C activator, also increased the activity of NSC MS . ET-1-or PMA-induced facilitation of NSC MS was abolished by GF109203X (10 μM), a protein kinase C inhibitor. Video analysis of pressurized cerebral artery showed inhibition of the myogenic response by the NSC MS channel blockers GsMTx-4 (5 μM) and DIDS (3-100 μM). Treatment with ET-1 (10 pM) augmented the myogenic response and this was inhibited by DIDS (30 μM). Conclusion: Stimulation of ET-1 receptor (ET A ) facilitates NSC MS via a protein kinase C-dependent signaling pathway in rabbit arterial myocytes. Our findings suggest that NSC MS play a role in the myogenic response and its augmentation by ET-1.

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“…12 The synthesis of ET-1 by endothelial cells is activated by physicochemical factors such as shear stress, hypoxia, and elevated oxidized low-density lipoproteins. 13,14 These stimuli may trigger ET-1-mediated vasospasms. Vasospasms are defined as vasoconstrictions that outlast the stimulus.…”

mentioning

confidence: 99%

Endothelin-1–Induced Vasospasms of Spiral Modiolar Artery Are Mediated by Rho-Kinase–Induced Ca ²⁺ Sensitization of Contractile Apparatus and Reversed by Calcitonin Gene–Related Peptide

Scherer

Herzog

Wangemann

2002

Stroke

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Background and Purpose-Vasospasms of the spiral modiolar artery may cause an ischemic stroke of the inner ear that manifests itself by a sudden hearing loss. Previously we have shown that endothelin-1 (ET-1) induces vasospasms of the spiral modiolar artery. Here we tested the hypotheses that ET-1-induced vasospasms are (1) reversible by ET A receptor antagonists; (2) mediated by a Ca 2ϩ sensitization of the contractile apparatus via a Rho-kinase-induced inhibition of myosin light chain phosphatase; and (3) reversible by the vasodilator calcitonin gene-related peptide (CGRP). Methods-The Ca 2ϩ sensitivity of the contractile apparatus was evaluated by correlation between the smooth muscle cell Ca 2ϩ concentration and the vascular diameter, which were measured by microfluorometry with the fluorescent dye fluo-4 and videomicroscopy, respectively. Results-ET-1-induced vasospasms were prevented but not reversed by the ET A receptor antagonists BQ-123 and BMS-182874. The Ca 2ϩ sensitivity of the contractile apparatus was increased by ET-1 and by inhibition of myosin light chain phosphatase with calyculin A and was decreased by CGRP. ET-1-induced vasospasms and Ca 2ϩ sensitization were prevented and reversed by the Rho-kinase antagonist Y-27632 and by CGRP. Conclusions-ET-1 induces vasospasms of the spiral modiolar artery via ET A receptor-mediated activation of Rho-kinase, inhibition of myosin light chain phosphatase, and an increase in Ca 2ϩ sensitivity, which is reversed by CGRP. The observation that vasospasms were reversed by Y-27632 but not by BQ-123 or BMS-182874 suggests that Rho-kinase, rather than the ET A receptor, is the most promising pharmacological target for the treatment of ET-1-induced vasospasms, ischemic strokes, and sudden hearing loss.

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Oxidized Low-Density Lipoprotein Enhances Myogenic Tone in the Rabbit Posterior Cerebral Artery Through the Release of Endothelin-1

Cited by 19 publications

References 54 publications

Endothelin-1 Is a Critical Mediator of Myogenic Tone in Tumor Arterioles

Endothelin-1 Is a Critical Mediator of Myogenic Tone in Tumor Arterioles

Mechanosensitive nonselective cation channel facilitation by endothelin-1 is regulated by protein kinase C in arterial myocytes

Endothelin-1–Induced Vasospasms of Spiral Modiolar Artery Are Mediated by Rho-Kinase–Induced Ca ²⁺ Sensitization of Contractile Apparatus and Reversed by Calcitonin Gene–Related Peptide

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Oxidized Low-Density Lipoprotein Enhances Myogenic Tone in the Rabbit Posterior Cerebral Artery Through the Release of Endothelin-1

Cited by 19 publications

References 54 publications

Endothelin-1 Is a Critical Mediator of Myogenic Tone in Tumor Arterioles

Endothelin-1 Is a Critical Mediator of Myogenic Tone in Tumor Arterioles

Mechanosensitive nonselective cation channel facilitation by endothelin-1 is regulated by protein kinase C in arterial myocytes

Endothelin-1–Induced Vasospasms of Spiral Modiolar Artery Are Mediated by Rho-Kinase–Induced Ca 2+ Sensitization of Contractile Apparatus and Reversed by Calcitonin Gene–Related Peptide

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Endothelin-1–Induced Vasospasms of Spiral Modiolar Artery Are Mediated by Rho-Kinase–Induced Ca ²⁺ Sensitization of Contractile Apparatus and Reversed by Calcitonin Gene–Related Peptide