Mild Hypercapnia Induces Vasodilation via Adenosine Triphosphate-sensitive K+Channels in Parenchymal Microvessels of the Rat Cerebral Cortex

Nakahata, Katsutoshi; Kinoshita, Hiroyuki; Hirano, Yusei; Kimoto, Yoshiki; Iranami, Hiroshi; Hatano, Yoshio

doi:10.1097/00000542-200312000-00014

Cited by 61 publications

(37 citation statements)

References 36 publications

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“…The potency of glibenclamide at SUR2 is one to 2 orders of magnitude less than at SUR1. 7 However, cerebrovascular SUR2-regulated K ATP channels have been shown in rodents to be important for hypoxic/hypercarbic cerebral vasodilation, 8,9 which in turn may be important for optimizing collateral blood flow after stroke. We hypothesized that potential vasoconstriction through this mechanism, if present, would not cause a deleterious effect.…”

mentioning

confidence: 99%

Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke

Kunte

Schmidt

Eliasziw

et al. 2007

Stroke

152

117

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Background and Purpose-The sulfonylurea receptor 1-regulated NC Ca-ATP channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume. We hypothesized that patients with type 2 diabetes mellitus taking sulfonylurea agents both at the time of stroke and during hospitalization would have superior outcomes. Methods-We reviewed medical records of patients with diabetes mellitus hospitalized within 24 hours of onset of acute ischemic stroke in the Neurology Clinic, Charité Hospital, Berlin, Germany, during 1994 to 2000. After exclusions, the cohort comprised 33 patients taking a sulfonylurea at admission through discharge (treatment group) and 28 patients not on a sulfonylurea (control group). The primary outcome was a decrease in National Institutes of Health Stroke Scale of 4 points or more from admission to discharge or a discharge National Institutes of Health Stroke Scale score of 0. The secondary outcome was a discharge modified Rankin Scale score Յ2. Results-No significant differences, other than stroke subtype, were observed among baseline variables between control and treatment groups. The primary outcome was reached by 36.4% of patients in the treatment group and 7.1% in the control group (Pϭ0.007). The secondary outcome was reached by 81.8% versus 57.1% (Pϭ0.035). Subgroup analyses showed that improvements occurred only in patients with nonlacunar strokes and were independent of gender, previous transient ischemic attack, and blood glucose levels. Conclusion-Sulfonylureas may be beneficial for patients with diabetes mellitus with acute ischemic stroke. Further investigation of similar cohorts and a prospective randomized trial are recommended to confirm the present observations. (Stroke. 2007;38:2526-2530.)Key Words: cerebral ischemia Ⅲ diabetes mellitus Ⅲ glibenclamide Ⅲ stroke Ⅲ sulfonylurea A cute stroke is the second leading cause of death in industrialized countries and is the leading medical cause of acquired adult disability. At present, thrombolysis is the only approved therapy, and for a variety of reasons, it is administered to less than 5% of patients with stroke. 1 There is an ongoing search for better prevention and treatment for acute stroke.The NC Ca-ATP channel is a nonselective cation channel that is expressed in the central nervous system only under conditions of injury or ischemia. [2][3][4] Channel opening, which is triggered by adenosine triphosphate depletion, results in cytotoxic edema, oncotic cell death, and cerebral edema. 5 Like the K ATP channel in pancreatic ␤ cells, it is regulated by sulfonylurea receptor 1 (SUR1) and is blocked by sulfonylureas such as glibenclamide (glyburide). Recently, Simard et al 4 reported that this channel is upregulated in rodent models of ischemic stroke, and that postevent block of the channel with glibenclamide reduces mortality, cerebral edema, and infarct volume by half.In patients with type 2 diabetes mellitus (DM), ...

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mentioning

confidence: 99%

Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke

Kunte

Schmidt

Eliasziw

et al. 2007

Stroke

152

117

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“…Vasoconstricting agonists produce similar levels of tone and vasomotion as are observed when intraluminal pressure and flow are applied to arterioles within slices through cannulation of individual vessels (Lovick et al 2005). Furthermore, pre-constricted arterioles in brain slices retain their characteristic responsiveness to extracellular K + (Nakahata et al 2006), and possess a functional complement of SMC K + channels (Filosa et al 2006,Nakahata et al 2003,Nakahata et al 2006. One obvious caveat to using this technique is that the level of vascular tone induced by the vasoconstricting agonist should mimic the level of tone generated in vivo in response to physiological pressure.…”

Section: Limitations Of Commonly Utilized Experimental Preparationsmentioning

confidence: 94%

Astrocytic Calcium Signaling: The Information Currency Coupling Neuronal Activity to the Cerebral Microcirculation

Straub

Nelson

2007

Trends in Cardiovascular Medicine

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In the brain, increased neuronal synaptic activity is accompanied by an increase in local cerebral blood flow that serves to satisfy neuronal metabolic demands. This linkage between neuronal activity and local blood flow has been appreciated for over 100 years. Although this process has been exploited clinically in the form of functional imaging techniques to map brain function, the mechanisms by which increased synaptic activity is communicated to the cerebral microcirculation to generate a vasodilatory response are poorly understood. Recent studies, however, have illuminated a central role for astrocytic calcium (Ca 2+ ) signals as mediators of this process of neurovascular coupling. This review highlights recent evidence implicating astrocytes in the regulation of intracerebral arteriolar diameter, with particular emphasis on the putative signaling molecules and pathways proposed to exert changes on arteriolar physiology.

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“…H/H may be accompanied by extra-and/or intracellular acidosis, leading to relaxation of the cerebrovascular smooth muscle (205). It was shown in intraparenchymal cerebral arterioles that, at normal pH, CO 2 fails to produce any significant vasodilation, indicating that it is the change in extracellular proton levels and not the CO 2 concentration that is responsible for the alteration of the vascular tone (157). The fast changes in pH that occur during hypercapnia were shown to modulate NO production, and it has been proposed that the extracellular pH may be the main trigger of hypercapnia-induced, NOdependent relaxation of the cerebral arteries (204,205).…”

Section: Regulatory Mechanisms Of the Cerebral Circulationmentioning

confidence: 99%

Endocannabinoids in cerebrovascular regulation

Benyó

Ruisanchez

Leszl-Ishiguro

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. cerebral circulation; endocannabinoids; cannabinoid receptors; TRPV1 channel; neurovascular unit THE CEREBRAL VASCULATURE HAS two main homeostatic functions: 1) to adjust the local blood supply to the eventually rapidly changing metabolic demands of neurons; and 2) to maintain an optimal extracellular environment in the brain. The former function is realized by the regulation of the local cerebral blood flow (CBF), whereas the latter is achieved by the maintenance of the blood-brain barrier (BBB) and related transport mechanisms. The endocannabinoid system has been implicated as an important regulatory component in both of these cerebrovascular functions. The roles of endocannabinoids and cannabinoid receptors in the BBB have been reviewed recently (237). Here we aim to overview our knowledge on the endocannabinoid-mediated regulation of cerebral circulation.

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Mild Hypercapnia Induces Vasodilation via Adenosine Triphosphate-sensitive K+Channels in Parenchymal Microvessels of the Rat Cerebral Cortex

Cited by 61 publications

References 36 publications

Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke

Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke

Astrocytic Calcium Signaling: The Information Currency Coupling Neuronal Activity to the Cerebral Microcirculation

Endocannabinoids in cerebrovascular regulation

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