LACK OF CHOLINERGIC REGULATION OF VASOPRESSIN AND NOREPINEPHRINE RESPONSES TO HYPERTONIC SALINE IN HUMANS

In vitro studies in hypothalamic-pituitary explants in the rat have su ggested cholinergic mediation of arginine vasopressin (AVP) osmoregula tion. In this study we attempted to demonstrate, in humans, cholinergi c mediation of AVP osmoregulation. Specifically, we tested the hypothe sis that the plasma AVP response to an osmolar stimulus would be atten uated by pharmacologic blockade of central nervous system muscarinic o r nicotinic receptors in humans. We also evaluated the effects of chol inergic blockade on the norepinephrine (NE) response to an osmolar sti mulus. Young normal males underwent hypertonic saline infusion followi ng administration of the centrally active muscarinic antagonist scopol amine or the centrally active nicotinic antagonist mecamylamine. Neith er mecamylamine nor scopolamine affected the AW response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dep endent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the e ffects of scopolamine and mecamylamine on the AVP and NE responses to physostigmine, a cholinesterase inhibitor which stimulates AVP release into plasma through a non-osmolar central nervous system cholinergic mechanism. Scopolamine eliminated the AVP response to physostigmine. M ecamylamine reduced NE concentrations both before and after scopolamin e administration but did not affect the slope of the AVP response. The se results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.