Soman-induced hypertension in conscious rats is mediated by prolonged central muscarinic stimulation

The acetylcholinesterase inhibitor, soman, induces marked and sustained hyp ertension and tachycardia associated with a convulsive syndrome in rats. Th e aims of the present study were to distinguish between the cardiovascular and convulsant effects of soman and to determine whether the maintenance of the soman-induced hypertension and tachycardia depends solely on a central muscarinic effect. To this end, using a computerised analysis of blood pre ssure (BP) in conscious freely moving rats, we examined the consequences on the increase in mean BP (MBP) and heart rate (HR) induced by soman (60 mu g/kg, i.v.) of I) a pre-treatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.) and 2) atropine sulphate (10 mg/kg, i.v.) administered 10 or 6 0 min after the intoxication. Pretreatment with diazepam prevented the conv ulsions, assessed by electroencephalogram (EEG) recording, but modified nei ther the magnitude nor the kinetics of the presser and tachycardic effects of soman (Delta MBP = 74 +/- 2 and 73 +/- 5 mmHg. 5 HR = 69 +/- 10 and 79 /- 7 bpm, maximum MBP = 186 +/- 3 and 182 +/- 6 mmHg. maximum HR = 545 +/- 9 and 522 +/- 16 bpm in solvent- (n = 8) and diazepam- (n = 8) pre-treated rats, respectively). Whatever its time of administration. atropine sulphate fully and immediately reversed the rise in BP induced by soman. The soman- induced tachycardia was also suppressed hy atropine administered 10 min aft er soman whereas it persisted when atropine was injected 60 min after the i ntoxication. These results show that the cardiovascular effects of soman ca n occur independently of the convulsive syndrome and that the maintenance o f the soman-induced hypertension depends entirely on a permanent central mu scarinic stimulation.