EFFECT OF INDOMETHACIN ON THE PITUITARY-ADRENOCORTICAL RESPONSE TO ADRENERGIC-STIMULATION

The role of prostaglandins (PGs) in stimulation of the hypothalamic-pi tuitary-adrenal (HPA) axis by adrenergic agonists and catecholamines w as investigated in nonanesthetized rats. The cyclooxygenase and PGs sy nthesis inhibitor indomethacin was given systemically or intracerebrov entricularly (icy) 15 min prior to phenylephrine (30 mu g), clonidine (10 mu g), and isoproterenol (20 mu g), an alpha(1)-, alpha(2)- and be ta-adrenergic receptor agonists, respectively, or noradrenaline (10 mu g) and adrenaline (10 mu g) Indomethacin given ip (2 mg/kg) or icy (1 0 mu g) almost abolished the increase in corticosterone secretion elic ited by phenylephrine, considerably reduced the response to clonidine but did not markedly affect the response to isoproterenol. Pretreatmen t with indomethacin by either route strongly suppressed the corticoste rone response to noradrenaline, but did not substantially affect the h ormonal response to adrenaline. The above data indicate that prostagla ndins considerably mediate the HPA axis response to central stimulatio n of alpha(1)- and alpha(2)-, but not beta-adrenergic receptors. They also point to significant involvement of prostaglandins in the noradre naline-, but not adrenaline-induced HPA response indicating that norad renaline stimulates the HPA axis predominantly via alpha(1)- and alpha (2)-adrenergic receptors, whereas adrenaline exerts stimulation mainly via beta-adrenergic receptors.