NEUROHYPOPHYSEAL AND PITUITARY-ADRENOCORTICAL RESPONSES TO THE ALPHA1-AGONIST METHOXAMINE IN HUMANS

To test the hypothesis that the release of neurohypophyseal peptides i nto plasma in humans is stimulated by a central nervous system (CNS) a lpha1 adrenergic mechanism, we measured the responses of arginine vaso pressin (AVP) and oxytocin (OT) to intravenous methoxamine, an alpha1 agonist which enters the CNS following peripheral administration. The potential confound of baroreceptor inhibition of AVP release by the pr essor effect of methoxamine was addressed by measuring the plasma AVP response to infusion of norepinephrine (NE), an alpha1 agonist which d oes not enter the CNS and which produced an equivalent pressor effect. We also assessed the pituitary adrenocortical system responses to met hoxamine and norepinephrine infusions by measuring plasma ACTH and cor tisol concentrations. In addition, plasma NE and epinephrine were meas ured. Methoxamine, but not NE, increased plasma AVP compared to placeb o infusion. Neither methoxamine nor NE affected plasma OT. The AVP ele vation was delayed until more than 60 min after the methoxamine infusi on began and the peak AVP level occurred 30 min after cessation of the infusion. In contrast, ACTH and cortisol increased early during metho xamine infusion and ACTH returned to baseline promptly after the infus ion ceased. Although it is possible that the AVP response to methoxami ne reflected stimulation of AVP release at a CNS level, it is also pos sible that the AVP increase represented a rebound response to withdraw al of methoxamine.