Session 4

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48

PROLONGED CENTRAL MUSCARINIC STIMULATION MEDIATES SOMAN-INDUCED HYPERTENSION IN FREELY MOVING RATS

R. Létienne. A. Bataillard. C. Julien C. Barrès G. Lallement* and J. Sassard

Département de Physiologie et Pharmacologie Clinique. ESA CNRS 5014, Faculté de Pharmacie, 8 avenue Rockefeller, 69373 Lyon Cedex 08 * Unité de Neurotoxicologie CRSSA. 24 avenue des Maquis du Grésivaudan BP 37,38702 La Tronche Cedex

The acetylcholinesterase inhibitor soman is known to induce a marked and sustained hypertension associated with a convulsive syndrome in conscious freely moving rats. The aim of the present study was, first, to determine whether the soman-induced hypertension depends solely on a central muscarinic stimulation or involves other neurotransmitters and, second, to distinguish between the hypertensive and convulsant effects of soman. To that end, we examined, using a computerized analysis of blood pressure in 28 conscious rats, the consequences on the hypertension induced by soman (60 µg/kg, i.v.) of injections of atropine sulfate (10 mg/kg, i.v.) administered at different times after the intoxication and of a pretreatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.). Whatever its time of administration, atropine sulfate fully and immediately reversed the rise in blood pressure induced by soman. Pretreatment with diazepam prevented the convulsions, assessed by electroencephalogram recording, but modified neither the magnitude nor the kinetics of the pressor effect of soman. These results show that the soman-induced hypertension depends on a permanent central muscarinic stimulation and can occur independently of the convulsive syndrome.

This research was supported by Direction des Recherches Etudes et Techniques contract n°95077

49

PHYSOSTIGMINE-INDUCED PRESSOR RESPONSE IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

E. Lazartigues, T. Tellioglus, C. Brefel-Courbonz, M.A. Tranz, J.L. Montastruc and O. Rascol

Laboratoire de Pharmacologie Médicale et Clinique, INSERM U455 et U3 17, Faculté de Médecine, Toulouse, France.

The mechanisms and subtypes of muscarinic receptors involved in the cardiovascular effects of physostigmine, a centrally acting acetylcholinesteraseinhibitor, were investigated in normotensive WKY and spontaneously hypertensive rats (SHR). Physostigmine (50 µg.kg-1 i.v.) induced a long lasting increase in blood pressure (BP), associated with a brief bradycardia. This increase in systolic and diastolic BP was maximal 5 min after drug administration and had a greater magnitude in SHR (+51±6 and +37±4 mmHg) than in WKY (+32±2 and +22±5 mmHg) rats (Student’s t test, P