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 suggested cholinergic mediation of arginine vasopressin (AVP) osmoregulation. In this study we attempted to demonstrate, in humans, cholinergic mediation of AVP osmoregulation. Specifically, we tested the hypothesis that the plasma AVP response to an osmolar stimulus would be attenuated by pharmacologic blockade of central nervous system muscarinic or nicotinic receptors in humans. We also evaluated the effects of cholinergic blockade on the norepinephrine (NE) response to an osmolar stimulus. Young normal males underwent hypertonic saline infusion following administration of the centrally active muscarinic antagonist scopolamine or the centrally active nicotinic antagonist mecamylamine. Neither mecamylamine nor scopolamine affected the AVP response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dependent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the effects 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. Mecamylamine reduced NE concentrations both before and after scopolamine administration but did not affect the slope of the AVP response. These results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.
Pascualy
M
M
Geriatric Research, Education, and Clinical Center, Seattle, WA, USA.
Peskind
E R
ER
Wingerson
D
D
van Belle
G
G
Veith
R C
RC
Dorsa
D M
DM
Raskind
M A
MA
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D009638:Norepinephrine / Q000097:blood*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012462:Saline Solution, Hypertonic; D012601:Scopolamine / Q000494:pharmacology; D014667:Vasopressins / Q000097:blood*
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D012462:Saline Solution, Hypertonic; D014667:Vasopressins; D010830:Physostigmine; D012601:Scopolamine; D009638:Norepinephrine