Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition.
The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.
Karlsson
Britt M
BM
Swedish Defence Research Agency, Division of NBC Defence, Department of Medical Countermeasures, Umeå, Sweden. Britt.Karlsson@foi.se
Koch
Mona
M
Koskinen
Lars-Owe D
LO
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009553:Nimodipine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012999:Soman / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction; D014664:Vasodilation
D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D009553:Nimodipine; D012999:Soman