Perfusion of the hypothalamic paraventricular nucleus with N-methyl-D-aspartate produces thromboxane A2 and centrally activates adrenomedullary outflow in rats

We applied a microdialysis technique for the measurement of hypothalamic th romboxane B2, a stable metabolite of thromboxane A2. in urethane-anesthetiz ed rats. Perfusion with N-methyl-D-aspartate (1.5 and 2.5 mM) of the parave ntricular nucleus by microdialysis probe concentration-dependently elevated the levels of thromboxane B2 in this region and plasma levels of catechola mines. The elevation of adrenaline was much more marked than that of noradr enaline. Pretreatment with dizocilpine maleate (0.1 mM), a non-competitive antagonist of N-methyl-D-aspartate receptors, of the paraventricular nucleu s by microdialysis probe attenuated the N-methyl-D-aspartate (1.5 mM)-induc ed elevations of both thromboxane B2 and plasma catecholamines. Intracerebr oventricular administration of furegrelate (250 mu g/animal), a thromboxane A2 synthase inhibitor, also abolished the responses evoked by N-methyl-D-a spartate. These results indicate that N-methyl-D-aspartate applied into the paraventr icular nucleus produces thromboxane A2 in this region and elevates plasma l evels of catecholamines, especially adrenaline. Thromboxane A2 produced in this hypothalamic nucleus is probably involved in the N-methyl-D-aspartate- induced central adrenomedullary outflow. (C) 2000 IBRO. Published by Elsevi er Science Ltd.