ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

Kitazono, Takanari; Heistad, D D; Faraci, Frank M.

doi:10.1161/01.hyp.22.5.677

Cited by 74 publications

(33 citation statements)

References 19 publications

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“…44 Also, dilation of pial arteries in response to RP52891, a K ATP channel activator, was observed to be impaired in diabetic rats, 45 whereas basilar artery dilation in response to aprikalim was blunted in stroke-prone spontaneously hypertensive rats. 46 Because K ϩ channels regulate the tone of cerebral blood vessels, 7 impaired vascular responsiveness to activators of these channels after brain injury suggests the contribution of such signal transduction mechanisms to stroke pathogenesis. It is presently uncertain, however, whether the observations made in the present study can be translated to the adult state or if they are unique to the perinate.…”

Section: Discussionmentioning

confidence: 99%

Vasopressin-Induced Protein Kinase C–Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury

Armstead

2001

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Background and Purpose-Pial artery dilation in response to activators of the ATP-sensitive K ϩ (K ATP ) and calciumsensitive K ϩ (K Ca ) channels is impaired after fluid percussion brain injury (FPI). Vasopressin, when coadministered with the K ATP and K Ca channel agonists cromakalim and NS1619 in a concentration approximating that observed in cerebrospinal fluid (CSF) after FPI, blunted K ATP and K Ca channel-mediated vasodilation. Vasopressin also contributes to impaired K ATP and K Ca channel vasodilation after FPI. In addition, protein kinase C (PKC) activation generates superoxide anion (O 2 Ϫ ), which in turn contributes to K ATP channel impairment after FPI. We tested whether vasopressin generates O 2 Ϫ in a protein kinase C (PKC)-dependent manner, which could link vasopressin release to impaired K ATP and K Ca channel-induced pial artery dilation after FPI. Methods-Injury of moderate severity (1.9 to 2.1 atm) was produced with the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O 2 Ϫ generation. Results-Under sham injury conditions, topical vasopressin (40 pg/mL, the concentration present in CSF after FPI) increased superoxide dismutase-inhibitable NBT reduction from 1Ϯ1 to 23Ϯ4 pmol/mm 2 . Chelerythrine (10 Ϫ7 mol/L, a PKC inhibitor) blunted such NBT reduction (1Ϯ1 to 9Ϯ2 pmol/mm 2 ), whereas the vasopressin antagonist l-(␤-mercapto-␤,␤-cyclopentamethylene propionic acid)2-(o-methyl)-Tyr-arginine vasopressin (MEAVP) blocked NBT reduction. Chelerythrine and MEAVP also blunted the NBT reduction observed after FPI (1Ϯ1 to 15Ϯ1, 1Ϯ1 to 4Ϯ1, and 1Ϯ1 to 5Ϯ1 pmol/mm 2 for sham-, chelerythrine-, and MEAVP-treated animals, respectively). Under sham injury conditions, vasopressin (40 pg/mL) coadministered with cromakalim or NS1619 blunted dilation in response to these K ϩ channel agonists, whereas chelerythrine partially restored such impaired vasodilation for cromakalim but not NS1619. Cromakalim-and NS1619-induced pial artery dilation also was blunted after FPI. MEAVP partially protected dilation to both K ϩ channel agonists after FPI, whereas chelerythrine did so for only cromakalim responses (for cromakalim at 10 Ϫ8 and 10 Ϫ6 mol/L, 13Ϯ1% and 23Ϯ1%, 2Ϯ1% and 5Ϯ1%, 9Ϯ1% and 15Ϯ2%, and 9Ϯ1% and 16Ϯ2% for sham-, FPI-, FPI-MEAVP-, and FPI-chelerythrine-pretreated animals, respectively). Conclusions-These data show that vasopressin, in concentrations present in CSF after FPI, increased O 2 Ϫ production in a PKC-dependent manner and contributes to such production after FPI. These data show that vasopressin contributes to K ATP but not K Ca channel function impairment in a PKC-dependent manner after FPI and suggest that vasopressin contributes to K Ca channel function impairment after FPI via a mechanism independent of PKC activation. (Stroke.

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Section: Discussionmentioning

confidence: 99%

Vasopressin-Induced Protein Kinase C–Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury

Armstead

2001

Stroke

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“…Delayed and inward-rectifying K ϩ channels have been postulated to contribute to the regulation of cerebrovascular tone, and glibenclamide-sensitive K ϩ channels also may modulate cerebrovascular excitability under some conditions. [39][40][41][42][43][44][45] To date, however, early studies in the SHR vasculature have not documented an enhanced K ϩ current through other types of K ϩ channels, which are insensitive to Ca 2ϩ activation. Rather, Martens and Gelband 11 have recently reported a reduced density of delayed-rectifier K ϩ current in renal arteries of SHR, and Kitazono et al 45 observed an impaired vasodilator function of glibenclamide-sensitive K ϩ channels in basilar arteries of stroke-prone SHR.…”

Section: Pressure-induced Upregulation May Be Specific To the K Ca Chmentioning

confidence: 99%

Increased Expression of Ca ²⁺ -Sensitive K ⁺ Channels in the Cerebral Microcirculation of Genetically Hypertensive Rats

Liu

Hudetz

Knaus

et al. 1998

Circulation Research

117

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Abstract-The Ca 2ϩ -sensitive K ϩ channel (K Ca channel) plays a key role in buffering pressure-induced constriction of small cerebral arteries. An amplified current through this channel has been reported in vascular smooth muscle cells obtained from hypertensive animals, implying that the expression or properties of K Ca channels may be regulated by in vivo blood pressure levels. In this study, we investigated this hypothesis and its functional relevance by comparing the properties, expression levels, and physiological role of K Ca channels in cerebral resistance arteries from normotensive and genetically hypertensive rats. Whole-cell patch-clamp experiments revealed a 4.7-fold higher density of iberiotoxinsensitive K Ca channel current at physiological membrane potentials in spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKY) rat cerebrovascular smooth muscle cells (nϭ18 and 21, respectively). However, additional single-channel analysis in detached patches showed similar levels of unitary conductance, voltage, and Ca 2ϩ sensitivity in K Ca channels from WKY and from SHR membranes. In contrast, Western analysis using an antibody directed against the K Ca channel ␣-subunit revealed a 4.1-fold increase in the corresponding 125-kD immunoreactive signal in cerebrovascular membranes from SHR compared with WKY rats. The functional impact of this enhanced K Ca channel expression was assessed in SHR and WKY rat pial arterioles, which were monitored by intravital microscopy through in situ cranial windows. Progressive pharmacological block of K Ca channels by iberiotoxin (0.1 to 100 nmol/L) dose-dependently constricted pial arterioles from SHR and WKY rats (nϭ6 to 8). The arterioles in SHR constricted 2-to 4-fold more intensely, and vasospasm occurred in some vessels. These data provide the first direct evidence that elevated levels of in situ blood pressure induce K Ca channel expression in cerebrovascular smooth muscle membranes. This homeostatic mechanism may critically regulate the resting tone of cerebral arterioles during chronic hypertension. Furthermore, the overexpression of distinct K ϩ channel types during specific cardiovascular pathologies may provide for the upregulation of novel disease-specific membrane targets for vasodilator therapies. (Circ Res. 1998;82:729-737.) Key Words: cerebral circulation Ⅲ K ϩ channel Ⅲ vascular smooth muscle Ⅲ hypertension Ⅲ iberiotoxin C erebral blood flow is maintained at normal or nearnormal levels during chronic hypertension, but the autoregulatory relationship is shifted to a higher pressure range, and vascular resistance is increased.

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“…2 Moreover, there is increasing evidence that K ϩ channel function may be variously altered in several disease states that predispose to stroke. 6 For example, cerebral vasorelaxation in response to openers of ATP-sensitive K ϩ channels is impaired during chronic hypertension, 7 diabetes, 8,9 atherosclerosis, 10 and after ischemia 11 or brain injury 12 but may be augmented after subarachnoid hemorrhage (SAH). [13][14][15] In addition, the function of inwardly rectifying K ϩ channels is impaired after ischemia and reper-…”

mentioning

confidence: 99%

Selective Effects of Subarachnoid Hemorrhage on Cerebral Vascular Responses to 4-Aminopyridine in Rats

Quan

Sobey

2000

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Background and Purpose-We postulated that some abnormalities in cerebrovascular function after subarachnoid hemorrhage (SAH) may involve underlying alterations in K ϩ channel function. Thus, using pharmacological inhibitors, we assessed the influence of SAH on function of 2 types of K ϩ channel in regulation of basilar artery diameter in vivo and membrane potential (E m ) in vitro. Methods-Rats were injected with saline (control) or autologous blood (SAH) into the cisterna magna. Two days later, effects of vasoactive drugs on the basilar artery were examined with a cranial window preparation. Vascular responses to 4-aminopyridine (4-AP), 3-aminopyridine (3-AP), tetraethylammonium (TEA), serotonin, acetylcholine, and adenosine were compared in control and SAH rats. Additional studies using intracellular microelectrodes evaluated the effects of 4-AP and serotonin on E m of basilar arteries isolated from control and SAH rats. Results-Baseline artery diameter was 236Ϯ5 m in control rats and 220Ϯ7 m in SAH rats (PϽ0.05). 4-AP, but not 3-AP, constricted the basilar artery in control rats, and responses to 4-AP were reduced in SAH rats. Constrictor responses to TEA or serotonin were unaffected by SAH. Vasodilator responses to acetylcholine were impaired in SAH rats, whereas responses to adenosine were not different. Resting E m was Ϫ81Ϯ3 mV in control arteries and Ϫ79Ϯ3 mV in SAH arteries. Both 4-AP and serotonin depolarized the basilar artery, but only 4-AP-induced depolarization was impaired in SAH arteries. Conclusions-These data suggest that 4-AP induces cerebral vasoconstriction in vivo through smooth muscle depolarization due to inhibition of voltage-dependent K ϩ channels. Furthermore, function of these K ϩ channels may be selectively reduced in the basilar artery after SAH and thus could contribute to cerebral vascular dysfunction.

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ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

Cited by 74 publications

References 19 publications

Vasopressin-Induced Protein Kinase C–Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury

Vasopressin-Induced Protein Kinase C–Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury

Increased Expression of Ca ²⁺ -Sensitive K ⁺ Channels in the Cerebral Microcirculation of Genetically Hypertensive Rats

Selective Effects of Subarachnoid Hemorrhage on Cerebral Vascular Responses to 4-Aminopyridine in Rats

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ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

Cited by 74 publications

References 19 publications

Vasopressin-Induced Protein Kinase C–Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury

Vasopressin-Induced Protein Kinase C–Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury

Increased Expression of Ca 2+ -Sensitive K + Channels in the Cerebral Microcirculation of Genetically Hypertensive Rats

Selective Effects of Subarachnoid Hemorrhage on Cerebral Vascular Responses to 4-Aminopyridine in Rats

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Increased Expression of Ca ²⁺ -Sensitive K ⁺ Channels in the Cerebral Microcirculation of Genetically Hypertensive Rats