Vasopressin induced cyclooxygenase dependent superoxide generation contributes to K + channel function impairment after brain injury

• Published in: Brain research 2001-08, Vol.910 (1), p.19-28
• Main Author: Armstead, William M
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arginine Vasopressin - analogs & derivatives; Arginine Vasopressin - pharmacology; Benzimidazoles - pharmacology; Biological and medical sciences; Blood - drug effects; Blood - metabolism; Brain Injuries - chemically induced; Brain Injuries - metabolism; Brain Injuries - physiopathology; Brain Ischemia - chemically induced; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Calcitonin Gene-Related Peptide - pharmacology; Cerebral Arteries - drug effects; Cerebral Arteries - metabolism; Cerebral Arteries - physiopathology; Cerebral circulation; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Cromakalim - pharmacology; Female; Indomethacin - pharmacology; Injuries of the nervous system and the skull. Diseases due to physical agents; K ATP and K ca channel; Male; Medical sciences; Newborn; Oxygen free radical; Potassium Channels - drug effects; Potassium Channels - metabolism; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism; Superoxides - metabolism; Swine; Traumas. Diseases due to physical agents; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - pharmacology; Vasopressins - antagonists & inhibitors; Vasopressins - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02716-0

This study determined if vasopressin generates superoxide anion (O − 2) in a cyclooxygenase dependent manner and if such production contributes to impairment of dilation to activators of ATP sensitive K + (K ATP) and calcium sensitive K + (K ca) channels following fluid percussion brain injury (FPI) in newborn pigs equipped with closed cranial windows. Superoxide dismutase (SOD) inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O − 2 generation. Under non-brain injury conditions, topical vasopressin (40 pg/ml, the concentration present in CSF following FPI) increased SOD inhibitable NBT reduction from 1±1 to 25±4 pmol/mm 2. Indomethacin, a cyclooxygenase inhibitor, blunted such NBT reduction (1±1 to 5±1 pmol/mm 2), while the vasopressin antagonist, l-(β-mercapto-β β-cyclopentamethylene propionic acid) 2-( o-methyl)-Tyr-AVP (MEAVP) blocked NBT reduction. MEAVP and indomethacin also blunted the NBT reduction observed after FPI. Under non-brain injury conditions, vasopressin (40 pg/ml) coadministered with the K ATP and K ca channel agonists, cromakalim and NS1619 (10 −8, 10 −6 M) diminished dilation to these K + channel agonists while indomethacin partially prevented such impairment (13±1 and 23±1 vs. 4±1 and 10±2 vs. 8±1 and 19±1% for cromakalim in untreated, vasopressin, and vasopressin plus indomethacin treated piglets, respectively). Cromakalim and NS1619 induced pial artery dilation was attenuated following FPI, while indomethacin or MEAVP preadministration partially prevented such impairment (13±1 and 23±1, sham control; 1±1 and 4±1, FPI; 8±1 and 16±3%, FPI–indomethacin pretreated for responses to cromakalim 10 −8, 10 −6 M, respectively). These data show that vasopressin increased O − 2 production in a cyclooxygenase dependent manner and contributed to this production after FPI. These data also show that vasopressin blunted K ATP and K ca channel mediated cerebrovasodilation in a cyclooxygenase dependent manner. These data suggest that vasopressin induced cyclooxygenase dependent O − 2 generation contributes to K ATP and K ca channel function impairment after FPI.