Role of Cl- in cerebral vascular tone and expression of Na+-K+-2Cl- co-transporter after neonatal hypoxia-ischemia

• Published in: Canadian journal of physiology and pharmacology Vol. 83; no. 8-9; pp. 767 - 773
• Main Authors: Dai, Yun, Tang, Jiping, Zhang, John H
• Format: Journal Article
• Language: English
• Published: Ottawa, Canada NRC Research Press 01.08.2005; National Research Council of Canada
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Bumetanide - pharmacology; Cerebral Arteries; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Chlorides - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Hypoxia - metabolism; In Vitro Techniques; Ischemia - metabolism; Isometric Contraction - drug effects; Male; Pregnancy; Rabbits; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Serotonin - pharmacology; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters - genetics; Sodium-Potassium-Chloride Symporters - metabolism; Solute Carrier Family 12, Member 2; Vertebrates: nervous system and sense organs; Oxygen; Neonatal; Serotonin; Central nervous system; Ion transport; Cardiovascular disease; Smooth muscle; Coupled transport; Inorganic element; Encephalon; Vertebrata; Mammalia; Ischemia; Sodium; Chlorides; Blood vessel; Neurotransmitter; Hypoxia; Circulatory system; Potassium; Carrier protein; Muscular tonus
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y05-076

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 - /HCO 3 - 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. Key words: serotonin, NCCK1, neonatal hypoxia.