Role of Cl- in cerebral vascular tone and expression of Na+-K+-2Cl- co-transporter after neonatal hypoxia-ischemia.
Chloride (Cl-) efflux induces depolarization and contraction of vascular smooth muscle cells. In the basilar arteries from the New Zealand white rabbits, the role of Cl- flux in serotonin-induced contraction was demonstrated by (i) inhibition of Na+-K+-2Cl- co-transporter (NKCC1) to decreased Cl- influx with bumetanide; (ii) a disabled Cl-/HCO3- exchanger with bicarbonate free HEPES solution; (iii) blockade of Cl- channels using 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and indanyloxyacetic acid 94, R-(+)-methylindazone (R-(+)-IAA-94); and (iv) substitution of extracellular Cl- with methanesulfonate acid (113 mmol/L; Cl-, 10 mmol/L). In addition, the expression of NKCC1 in brain tissues after neonatal hypoxia-ischemia was examined at mRNA and protein levels using RT-PCR and Western blotting techniques. NKCC1 mRNA and protein expressions were increased at 24 and 48 h and returned to normal levels at 72 h after hypoxia insult when compared with the control littermates. In conclusion, Cl- efflux regulates cerebral circulation and the up-regulation of NKCC1 after neonatal hypoxia-ischemia may contribute to brain injury.
Dai
Yun
Y
Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Tang
Jiping
J
Zhang
John H
JH
D000818:Animals; D000831:Animals, Newborn; D002034:Bumetanide / Q000494:pharmacology; D002536:Cerebral Arteries; D002712:Chlorides / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2
D002712:Chlorides; D012333:RNA, Messenger; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D012701:Serotonin