PMID: 7528658Jul 1, 1994Paper

Inhibition of NO synthase increases the severity of kainic acid-induced seizures in rodents

Epilepsy Research
L P PenixS Subramaniam

Abstract

The nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (NNA) and the putative brain-selective NO synthase inhibitor 7-nitroindazole (7-NI) were used to determine the role of endogenous NO on seizures induced by kainic acid (KA) in rats and KA, pilocarpine, bicuculline, picrotoxin and pentylenetetrazole (PTZ) in mice. Rats given a subconvulsant dose of KA (6 mg/kg, i.p.) had seizures after they had been pretreated with NNA (50 mg/kg, i.p.). With a higher dose of KA (12 mg/kg, i.p.), NNA caused an increase in wild running seizures and mortality. Unlike NNA, 7-NI had no effect on KA-induced seizures. Similarly, NNA but not 7-NI caused a worsening of seizures in mice measured as a shortening of seizure latency and an increase in wild running and mortality. The effect of NNA on seizure latency was completely reversed by the competitive substrate for NO synthase, L-arginine. NNA had no effect on seizure latency following any of the other convulsants and increased mortality following pilocarpine and picrotoxin alone. Our results indicate that NNA may enhance the severity of KA-induced seizures through suppression of NO synthase activity in the vascular endothelium. The resulting impairment of cerebrovascular autoregulation ...Continue Reading

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Citations

Mar 1, 1996·Pharmacology, Biochemistry, and Behavior·S HaraT Endo
Aug 1, 1996·Pharmacology, Biochemistry, and Behavior·G LallementJ H McDonough
Apr 20, 2000·European Journal of Pharmacology·G De SarroA De Sarro
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Feb 2, 2002·Epilepsy Research·Houman HomayounAhmad Reza Dehpour
Jul 20, 2002·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Piotr TutkaMarian Wielosz
Sep 7, 2013·Critical Reviews in Food Science and Nutrition·Mayur VirarkarAtif B Awad
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Jul 18, 2000·Epilepsia·H FaradjiR Cespuglio
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Oct 9, 2013·Neurochemical Research·Awanish Mishra, Rajesh Kumar Goel

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