-
Je něco špatně v tomto záznamu ?
Role of Kv7 channels in responses of the pulmonary circulation to hypoxia
V. Sedivy, S. Joshi, Y. Ghaly, R. Mizera, M. Zaloudikova, S. Brennan, J. Novotna, J. Herget, AM. Gurney,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NT13358
MZ0
CEP - Centrální evidence projektů
Odkazy
PubMed
25361569
DOI
10.1152/ajplung.00362.2013
Knihovny.cz E-zdroje
- MeSH
- aminopyridiny farmakologie MeSH
- analgetika farmakologie MeSH
- arteria pulmonalis metabolismus patologie patofyziologie MeSH
- blokátory draslíkových kanálů farmakologie MeSH
- cévní rezistence účinky léků MeSH
- draslíkové kanály KCNQ antagonisté a inhibitory metabolismus MeSH
- hladké svalstvo metabolismus patologie patofyziologie MeSH
- hypoxie * metabolismus patologie patofyziologie MeSH
- indoly farmakologie MeSH
- krysa rodu rattus MeSH
- membránové potenciály účinky léků MeSH
- plíce * krevní zásobení metabolismus patologie patofyziologie MeSH
- plicní hypertenze metabolismus patologie patofyziologie MeSH
- plicní oběh * MeSH
- potkani Wistar MeSH
- pyridiny farmakologie MeSH
- regulace genové exprese účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circulation to become hypertensive. Responses to airway hypoxia are associated with depolarization of smooth muscle cells in the pulmonary arteries and reduced activity of K(+) channels. As Kv7 channels have been proposed to play a key role in regulating the smooth muscle membrane potential, we investigated their involvement in the development of HPV and hypoxia-induced pulmonary hypertension. Vascular effects of the selective Kv7 blocker, linopirdine, and Kv7 activator, flupirtine, were investigated in isolated, saline-perfused lungs from rats maintained for 3-5 days in an isobaric hypoxic chamber (FiO2 = 0.1) or room air. Linopirdine increased vascular resistance in lungs from normoxic, but not hypoxic rats. This effect was associated with reduced mRNA expression of the Kv7.4 channel α-subunit in hypoxic arteries, whereas Kv7.1 and Kv7.5 were unaffected. Flupirtine had no effect in normoxic lungs but reduced vascular resistance in hypoxic lungs. Moreover, oral dosing with flupirtine (30 mg/kg/day) prevented short-term in vivo hypoxia from increasing pulmonary vascular resistance and sensitizing the arteries to acute hypoxia. These findings suggest a protective role for Kv7.4 channels in the pulmonary circulation, limiting its reactivity to pressor agents and preventing hypoxia-induced pulmonary hypertension. They also provide further support for the therapeutic potential of Kv7 activators in pulmonary vascular disease.
Department of Biochemistry Charles University 2nd Faculty of Medicine Prague Czech Republic
Department of Pathophysiology Charles University 2nd Faculty of Medicine Prague Czech Republic
Department of Physiology Charles University 2nd Faculty of Medicine Prague Czech Republic
Faculty of Life Sciences University of Manchester Manchester United Kingdom
- 000
- 00000naa a2200000 a 4500
- 001
- bmc15014014
- 003
- CZ-PrNML
- 005
- 20190920125426.0
- 007
- ta
- 008
- 150420s2015 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1152/ajplung.00362.2013 $2 doi
- 035 __
- $a (PubMed)25361569
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Šedivý, Vojtěch $u Department of Physiology, Charles University - Second Faculty of Medicine, Prague, Czech Republic; Department of Paediatrics, Charles University - Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic; and vojtech.sedivy@seznam.cz. $7 xx0216304
- 245 10
- $a Role of Kv7 channels in responses of the pulmonary circulation to hypoxia / $c V. Sedivy, S. Joshi, Y. Ghaly, R. Mizera, M. Zaloudikova, S. Brennan, J. Novotna, J. Herget, AM. Gurney,
- 520 9_
- $a Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circulation to become hypertensive. Responses to airway hypoxia are associated with depolarization of smooth muscle cells in the pulmonary arteries and reduced activity of K(+) channels. As Kv7 channels have been proposed to play a key role in regulating the smooth muscle membrane potential, we investigated their involvement in the development of HPV and hypoxia-induced pulmonary hypertension. Vascular effects of the selective Kv7 blocker, linopirdine, and Kv7 activator, flupirtine, were investigated in isolated, saline-perfused lungs from rats maintained for 3-5 days in an isobaric hypoxic chamber (FiO2 = 0.1) or room air. Linopirdine increased vascular resistance in lungs from normoxic, but not hypoxic rats. This effect was associated with reduced mRNA expression of the Kv7.4 channel α-subunit in hypoxic arteries, whereas Kv7.1 and Kv7.5 were unaffected. Flupirtine had no effect in normoxic lungs but reduced vascular resistance in hypoxic lungs. Moreover, oral dosing with flupirtine (30 mg/kg/day) prevented short-term in vivo hypoxia from increasing pulmonary vascular resistance and sensitizing the arteries to acute hypoxia. These findings suggest a protective role for Kv7.4 channels in the pulmonary circulation, limiting its reactivity to pressor agents and preventing hypoxia-induced pulmonary hypertension. They also provide further support for the therapeutic potential of Kv7 activators in pulmonary vascular disease.
- 650 _2
- $a aminopyridiny $x farmakologie $7 D000631
- 650 _2
- $a analgetika $x farmakologie $7 D000700
- 650 _2
- $a zvířata $7 D000818
- 650 12
- $a hypoxie $x metabolismus $x patologie $x patofyziologie $7 D000860
- 650 _2
- $a regulace genové exprese $x účinky léků $7 D005786
- 650 _2
- $a plicní hypertenze $x metabolismus $x patologie $x patofyziologie $7 D006976
- 650 _2
- $a indoly $x farmakologie $7 D007211
- 650 _2
- $a draslíkové kanály KCNQ $x antagonisté a inhibitory $x metabolismus $7 D051656
- 650 12
- $a plíce $x krevní zásobení $x metabolismus $x patologie $x patofyziologie $7 D008168
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a membránové potenciály $x účinky léků $7 D008564
- 650 _2
- $a hladké svalstvo $x metabolismus $x patologie $x patofyziologie $7 D009130
- 650 _2
- $a blokátory draslíkových kanálů $x farmakologie $7 D026902
- 650 _2
- $a arteria pulmonalis $x metabolismus $x patologie $x patofyziologie $7 D011651
- 650 12
- $a plicní oběh $7 D011652
- 650 _2
- $a pyridiny $x farmakologie $7 D011725
- 650 _2
- $a krysa rodu Rattus $7 D051381
- 650 _2
- $a potkani Wistar $7 D017208
- 650 _2
- $a cévní rezistence $x účinky léků $7 D014655
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Joshi, Shreena $u Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom;
- 700 1_
- $a Ghaly, Youssef $u Department of Physiology, Charles University - Second Faculty of Medicine, Prague, Czech Republic;
- 700 1_
- $a Mizera, Roman $u Department of Physiology, Charles University - Second Faculty of Medicine, Prague, Czech Republic; $7 xx0227543
- 700 1_
- $a Žaloudíková, Marie, $u Department of Pathophysiology, Charles University - Second Faculty of Medicine, Prague, Czech Republic; $d 1971- $7 xx0206604
- 700 1_
- $a Brennan, Sean $u Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom;
- 700 1_
- $a Novotna, Jana $u Department of Biochemistry, Charles University - Second Faculty of Medicine, Prague, Czech Republic.
- 700 1_
- $a Herget, Jan, $u Department of Physiology, Charles University - Second Faculty of Medicine, Prague, Czech Republic; $d 1945-2019 $7 nlk19990073223
- 700 1_
- $a Gurney, Alison M $u Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom;
- 773 0_
- $w MED00000288 $t American journal of physiology. Lung cellular and molecular physiology. Lung cellular and molecular physiology $x 1522-1504 $g Roč. 308, č. 1 (2015), s. L48-57
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/25361569 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20150420 $b ABA008
- 991 __
- $a 20190920125819 $b ABA008
- 999 __
- $a ok $b bmc $g 1071595 $s 896892
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2015 $b 308 $c 1 $d L48-57 $i 1522-1504 $m American journal of physiology. Lung cellular and molecular physiology $n Am J Physiol Lung Cell Mol Physiol $x MED00000288 $o Lung cellular and molecular physiology
- GRA __
- $a NT13358 $p MZ0
- LZP __
- $a Pubmed-20150420