cyclic-gmp and Syndrome

We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects.. Nine patients with CSX and 14 control subjects underwent a continuous infusion of L-arginine (0.125 g/min) or saline for 120 minutes. Sixty minutes after L-arginine or saline infusions, an intravenous insulin bolus (0.1 U/kg) combined with a euglycemic clamp was performed. Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls. At the end of the first hour of infusion, compared with saline, L-arginine infusion increased basal forearm blood flow, nitrite and nitrate (NOx), and forearm cGMP release and decreased endothelin-1. After insulin bolus, during saline, insulin-induced NOx, endothelin-1, and forearm cGMP release was almost abolished. Conversely, L-arginine restored a physiological profile of all endothelial variables compared with control subjects. In control subjects, compared with saline infusion, L-arginine infusion did not modify any parameter. ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release.. Plasma ADMA levels are increased in patients with CSX, and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP, effects that are reversed by intravenous L-arginine. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.

Topics: Angina Pectoris; Arginine; Blood Pressure; Coronary Angiography; Cyclic GMP; Endothelin-1; Endothelium, Vascular; Female; Forearm; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged; Nitric Oxide; Regional Blood Flow; Syndrome

The involvement of C-fiber afferent pathways in urinary frequency and pain associated with painful bladder syndrome raises the possibility of multiple targets for the treatment of this disease. Using an in vivo measurement of bladder activity as well as whole-cell patch clamp recording techniques to examine the properties of bladder afferent neurons in animal models of chronic cystitis, we have documented that tetrodotoxin-resistant sodium channels encoded by the Na(v) 1.8 (PN3/SNS) gene and nitric oxide acting via a cyclic guanosine monophosphate (cGMP)-dependent mechanism are important in modulating bladder pain responses. Thus, suppression of C-fiber afferent nerve activity by blocking specific sodium channels, elevating nitric oxide levels, or activating cGMP-dependent pathways might represent novel strategies for the treatment of symptoms in patients with painful bladder syndrome. Another treatment strategy is suppression of release or activity of proinflammatory agents that can cause normally unexcitable C-fiber afferents to become hyperactive or hyperexcitable. This approach to management of bladder pain was tested in patients with painful bladder syndrome by examining the effectiveness of the antiallergic agent suplatast tosilate (IPD-1151T), which suppresses urinary frequency in a rat model of cystitis. IPD-1151T is an immunoregulator that suppresses cytokine production in T-helper 2 cells and inhibits immunoglobulin E antibody formation and antigen-induced histamine release from mast cells. Preliminary data from an open-label clinical trial showed that 16 of 23 (70%) patients responded to treatment with IPD-1151T (300 mg/day orally for 12 months). The finding that expression of platelet-derived endothelial cell growth factor, which can activate mast cells, was lower in the bladder of responders than nonresponders indicates that bladder levels of platelet-derived endothelial cell growth factor may be a useful marker for this disease.

Topics: Afferent Pathways; Anti-Allergic Agents; Arylsulfonates; Cyclic GMP; Humans; Nerve Fibers; Nitric Oxide; Oligodeoxyribonucleotides, Antisense; Pain; Sodium Channel Blockers; Sulfonium Compounds; Syndrome; Urinary Bladder; Urinary Bladder Diseases; Urination Disorders

Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and a model of prolonged parasympatholytic syndrome, by administration of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we found significantly increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and T48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/microg creatinine); norepinephrine urinary excretion between T24h and T48h was decreased (-44%); the increase in cGMP urinary excretion was not significantly modified by the NO-synthase inhibitor, L-nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated rats. The link between these modifications in cGMP excretion and muscarinic receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP excretion could be tested as screening parameter in infants at risk of faint episodes associated with bradycardia.

Topics: Animals; Autonomic Nervous System Diseases; Cyclic GMP; Dose-Response Relationship, Drug; Heart Rate; Hemodynamics; Male; Muscarinic Agonists; Muscarinic Antagonists; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Norepinephrine; Parasympathetic Nervous System; Parasympatholytics; Piperidines; Rats; Rats, Sprague-Dawley; Reserpine; Syndrome

Noradrenergic and GABA-ergic systems were correlated and dominated in the processes of spinal cord segmentary apparatus superactivity compensation. An increase in c-GMP content in the spinal cord suggests an intensification of the activation mechanism. An increase in the c-AMP content may suggest an inhibition of the compensatory intensification of noradrenergic or GABA-ergic mechanisms.

Topics: 5,7-Dihydroxytryptamine; Amputation, Surgical; Amputation, Traumatic; Animals; Cyclic AMP; Cyclic GMP; Male; Norepinephrine; Oxidopamine; Rats; Receptors, Adrenergic; Receptors, GABA-A; Serotonin; Spinal Cord; Syndrome; Time Factors

Topics: Animals; Behavior, Animal; Brain; Brain Chemistry; Catecholamines; Cerebrovascular Circulation; Cyclic GMP; Dyskinesia, Drug-Induced; Electroencephalography; Glucose; Ion Channels; Pyrethrins; Rats; Structure-Activity Relationship; Syndrome

Topics: Animals; Arachidonic Acids; Binding Sites; Calcium; Cattle; Chediak-Higashi Syndrome; Chemotactic Factors; Chemotaxis; Chemotaxis, Leukocyte; Complement C5; Cyclic AMP; Cyclic GMP; Cytochalasin B; Humans; Hypergammaglobulinemia; Kartagener Syndrome; Mice; Oligopeptides; Potassium; Rabbits; Syndrome

Topics: Cyclic AMP; Cyclic GMP; Humans; Peritonitis; Practolol; Syndrome