Role of nitric oxide synthase isoforms for ophthalmic artery reactivity in mice

Laspas, Panagiotis; Goloborodko, Evgeny; Sniatecki, Jan J.; Kordasz, Marcin; Manicam, Caroline; Wojnowski, Leszek; Li, Huige; Patzak, Andreas; Pfeiffer, Norbert; Gericke, Adrian

doi:10.1016/j.exer.2014.06.018

Cited by 20 publications

(16 citation statements)

References 58 publications

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“…In retrospect, our investigation has shown that the eNOS isoform contributes to the vasodilatory responses of the ophthalmic artery of wild type mice (C57Bl/6J). Additionally, we also found that the endothelium-dependent vasodilation of the ophthalmic artery is retained in eNOS−/− mice 23 . This was followed by a recent study of ours that delved further to demonstrate that apart from eNOS, an array of EDHFs and potassium ion channels contributes to the maintenance of vascular reactivity to acetylcholine (ACh) in the ophthalmic artery of wild type mice 24 .…”

Section: Introductionsupporting

confidence: 61%

“…The mouse ophthalmic artery shares some important morphological and functional similarities with that of human’s. It has been elegantly shown in many studies that the ophthalmic artery emanates from the internal carotid artery in both humans and mice 25 – 27 , and that NO is a crucial modulator of vascular tone in both species 8 , 23 , 24 . Since the ophthalmic artery is one of the major blood suppliers of the eye 28 , any dysfunction in this arterial bed is implicated in the pathophysiology of an array of disorders, including but not only limited in the eye, such as transient retinal ischemia caused by ophthalmic artery occlusion, severe ipsilateral internal carotid artery stenosis or occlusion and, secondary collateral ophthalmic artery flow is an indication of impaired cerebral hemodynamics in stroke patients 29 – 32 .…”

Section: Introductionmentioning

confidence: 99%

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Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice

Manicam

Ginter

et al. 2017

Sci Rep

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Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Interestingly, dilatory responses were also retained in eNOS gene-deficient mice (eNOS−/−), indicating inherent endothelial adaptive mechanism(s) that act as back-up systems in chronic absence of eNOS to preserve vasorelaxation. Thus, this study endeavoured to identify the compensatory mechanism(s) in the ophthalmic artery of eNOS−/− mice employing isolated arterial segments and pharmacological inhibitors in vitro. Endothelium removal virtually abolished acetylcholine (ACh)-induced vasodilation, suggesting an obligatory involvement of the endothelium in cholinergic control of vascular tone. However, non-NOS and non-cyclooxygenase components compensate for eNOS deficiency via endothelium-derived hyperpolarizing factors (EDHFs). Notably, arachidonic acid-derived metabolites of the 12-lipoxygenase pathway were key mediators in activating the inwardly rectifying potassium channels to compensate for chronic lack of eNOS. Conclusively, endothelium-dependent cholinergic responses of the ophthalmic artery in the eNOS−/− mice are largely preserved and, this vascular bed has the ability to compensate for the loss of normal vasodilator responses solely via EDHFs.

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Section: Introductionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice

Manicam

Ginter

et al. 2017

Sci Rep

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“…In recent years, with the use of gene-knockout mice and isoform-selective NOS inhibitors, we demonstrated that endothelium-dependent vasodilation induced by ACh is mediated predominantly by the activation of endothelial NOS (eNOS) in the retinal arterioles 22 . However, in the mouse ophthalmic artery, eNOS mediated only a part of the cholinergic vasodilation response while another, yet unknown, mechanism also substantially contributed towards ACh-induced vasodilation 23 .The mouse ophthalmic artery is a small vessel with an inner diameter between 80 and 150 μm that develops moderate myogenic tone 24 25 26 . Since the relative contribution of these three mediators to agonist-induced vasodilation varies among vascular beds, species and also the diameter of the blood vessels, we hypothesize that PGI 2 and EDHFs may be of physiological relevance in the mouse ophthalmic circulation.…”

mentioning

confidence: 99%

The Gatekeepers in the Mouse Ophthalmic Artery: Endothelium-Dependent Mechanisms of Cholinergic Vasodilation

Manicam

Staubitz

Brochhausen

et al. 2016

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Cholinergic regulation of arterial luminal diameter involves intricate network of intercellular communication between the endothelial and smooth muscle cells that is highly dependent on the molecular mediators released by the endothelium. Albeit the well-recognized contribution of nitric oxide (NO) towards vasodilation, the identity of compensatory mechanisms that maintain vasomotor tone when NO synthesis is deranged remain largely unknown in the ophthalmic artery. This is the first study to identify the vasodilatory signalling mechanisms of the ophthalmic artery employing wild type mice. Acetylcholine (ACh)-induced vasodilation was only partially attenuated when NO synthesis was inhibited. Intriguingly, the combined blocking of cytochrome P450 oxygenase (CYP450) and lipoxygenase (LOX), as well as CYP450 and gap junctions, abolished vasodilation; demonstrating that the key compensatory mechanisms comprise arachidonic acid metabolites which, work in concert with gap junctions for downstream signal transmission. Furthermore, the voltage-gated potassium ion channel, Kv1.6, was functionally relevant in mediating vasodilation. Its localization was found exclusively in the smooth muscle. In conclusion, ACh-induced vasodilation of mouse ophthalmic artery is mediated in part by NO and predominantly via arachidonic acid metabolites, with active involvement of gap junctions. Particularly, the Kv1.6 channel represents an attractive therapeutic target in ophthalmopathologies when NO synthesis is compromised.

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“…Since the half-life of NO is very short (about 6-30 s), the NO production in the endothelium mainly depends on the activity of the key enzyme eNOS (Laspas et al, 2014). The regulation mechanism of eNOS activity is extremely complex.…”

Section: Discussionmentioning

confidence: 99%

Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro

Zhu

Song

et al. 2020

Front. Pharmacol.

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Role of nitric oxide synthase isoforms for ophthalmic artery reactivity in mice

Cited by 20 publications

References 58 publications

Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice

Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice

The Gatekeepers in the Mouse Ophthalmic Artery: Endothelium-Dependent Mechanisms of Cholinergic Vasodilation

Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro

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