Cerebral microvascular effects of nimodipine in combination with soman.

Nimodipine, a calcium antagonist, has been shown to increase the detoxification of soman. In this study the cerebral microcirculatory effects of nimodipine and the acetylcholinesterase inhibitor soman was studied. Anaesthetised rats were administered nimodipine, 10 mg kg(-1) or vehicle intra-peritoneally, and 1h later exposed to 45 µg kg(-1) soman intravenously. The regional blood flows were measured using the microsphere method. Nimodipine and soman markedly increased the cerebral blood flow (CBF) and reduced the vascular resistance. Total CBF increased by 146% after nimodipine and by 105% after soman administration. Combined administration of nimodipine and soman caused additional but not fully additive effects on CBF and vascular resistance, indicating possible different mechanisms of the two agents. A part of the nimodipine induced increased detoxification after AChE-inhibition may be associated with this cerebral vasodilation.

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.

Nitric oxide inhibition by L-NAME but not 7-NI induces a transient increase in cortical cerebral blood flow and affects the cerebrovasodilation induced by TRH.

The tripeptide thyrotropin releasing hormone (TRH) has multiple interesting and complex physiological effects. One of these is the cerebrovasodilating effect, which has been described under several different conditions. The final mechanism for this effect is unknown. In the present study, we found an initial atropine-resistant cerebral vasodilation (24%) elicited by the NOS inhibitor L-NAME in the rat. D-NAME and 7-NI did not produce this effect. TRH (300 microg kg(-1), i.v.) induced an increase in cerebral blood flow by 62%. L-NAME reduced this effect significantly. The cerebrovasodilating mechanism of TRH, at least in part, is endothelial NO dependent as the neuronal 7-NI NOS inhibitor does not affect the TRH response.