Cyclic guanosylmonophosphate urinary excretion in parasympathicomimetic orparasympatholytic syndromes induced by reserpine or diphemanil-methylsulfate

Parasympathetic hyperactivity is found in some infants presenting faint epi sodes and could be responsible of certain Sudden Infant Death Syndrome case s. Therefore it was interesting to look for a noninvasive biochemical indic ator of parasympathetic activity. A parasympaticomimetic syndrome associate d with muscarinic receptor stimulation, which has been followed during 48h, was obtained in the awake rat by reserpine injection (6.25mg/kg at T-0 and T-24h), and a model of prolonged parasympatholytic syndrome, by administra tion of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, i n drinking water (mean daily dosis: 150mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we fo und significantly increased cyclic guanosylmonophosphate (cGMP) urinary exc retion between T-24h and T-48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/mu g c reatinine); norepinephrine urinary excretion between T-24h and T-48h was de creased (-44%); the increase in cGMP urinary excretion was not significantl y modified by the NO-synthase inhibitor, L-nitro-arginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) an d increased norepinephrine urinary excretion (+61%). Thus cGMP excretion va ried in opposite directions in the reserpine- and DPMS-treated rats. The li nk between these modifications in cGMP excretion and muscarinic receptor st imulation or blockade has still to be fully demonstrated. Urinary cGMP excr etion could be tested as screening parameter in infants at risk of faint ep isodes associated with bradycardia.