cyclic-gmp and Gout

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Bacteria; Coenzyme A Ligases; Cyclic GMP; Energy Metabolism; Gout; Guanine Nucleotides; Guanosine Triphosphate; Humans; Microtubules; Nucleoside Diphosphate Sugars; Phosphoenolpyruvate Carboxykinase (GTP); Plants; Protein Biosynthesis; Purines; Ribosomes; Structure-Activity Relationship; Subcellular Fractions; Succinates

The role of nitric oxide (NO) in the antinociceptive effect of indomethacin was assessed in the pain-induced functional impairment model in the rat (PIFIR model), a model of inflammatory and chronic pain similar to that observed in clinical gout. Oral administration of indomethacin (5.6 mg/kg), a nonselective cyclooxygenase inhibitor, significantly decreased the nociceptive response elicited by uric acid injected into the knee joint of the right hind limb (2.0+/-3.0 and 149.7+/-18.0 area units [au], in the absence and the presence of indomethacin, respectively). This effect of indomethacin was reduced in nearly 50% by local pretreatment with the nonselective inhibitor of NO synthase, N G-L-nitro-arginine methyl ester (L-NAME) (72.9+/-10.7 vs. 149.7+/-18.0 au, P<0.05). On the other hand, local administration of L-arginine (a NO synthase substrate) or sodium nitroprusside (a non-enzymatic NO donor) each increased in almost 40% the antinociceptive effect of indomethacin (230.9+/-12.6 and 226.6+/-9.7 vs. 149.7+/-18.0 au, P<0.05), whereas D-arginine (the inactive isomer of arginine) had no effect on the indomethacin antinociceptive response (208.0+/-34.9 vs. 149.7+/-18.0 au). These results suggest that, the antinociceptive effect of indomethacin involves, at least in part, the NO-cyclic GMP pathway at peripheral level.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginine; Chronic Disease; Cyclic GMP; Disease Models, Animal; Enzyme Inhibitors; Female; Gout; Indomethacin; Nerve Tissue Proteins; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitroprusside; Pain; Pain Measurement; Peripheral Nervous System; Rats; Rats, Wistar; Signal Transduction; Uric Acid

In experiments conducted on male Wistar rats for elucidation the role of central mechanisms in development alterations of heart electric stability was studied activity of 5(1)-nucleotidase and adenosine desaminase in sensomotor cortex, hypothalamus and hippocamp. Were shown that changes of heart function were in case increased adenosine content in neurons of sensomotor cortex, hypothalamus and hippocamp. Introduction to animals with hyperuricemia DOCA, with activate 5(1)-nucleotidase and adenosine desaminase, was accompanied by changes of cAMP and cGMP content in neurons. Developing alterations of heart electric stability suggest the responsibility of injury adenosine metabolism in different brain structures of animals with hyperuricemia in alterations of central regulatory mechanisms of systemic blood flow.

Topics: Adenosine; Animals; Blood Circulation; Brain; Brain Chemistry; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Electrophysiology; Gout; Heart; Male; Rats; Time Factors; Uric Acid

Topics: Adult; Cyclic AMP; Cyclic GMP; Female; Gout; Humans; Male; Middle Aged; Uric Acid