Phenotypic identification of rat rostroventrolateral medullary presympathetic vasomotor neurons inhibited by exogenous cholecystokinin.
Systemic administration of the gastrointestinal hormone cholecystokinin (CCK) selectively inhibits splanchnic sympathetic vasomotor discharge and differentially affects presympathetic vasomotor neurons of the rostroventrolateral medulla (RVLM). Stimulation of the sympathoexcitatory region of the periaqueductal grey (PAG) produces profound mesenteric vasoconstriction. In this study, our aim was to identify phenotypically different populations of RVLM presympathetic vasomotor neurons using juxtacellular neuronal labelling and immunohistochemical detection of the adrenergic neuronal marker phenylethanolamine-N-methyl transferase (PNMT) and to determine whether the PAG provides functional excitatory input to these neurons. Fifty-eight percent (36/62) of RVLM presympathetic neurons were inhibited by systemic administration of CCK. These cells had conduction velocities (3.6 +/- 0.2 m/sec) in the non-C-fiber range consistent with neurons possessing lightly myelinated spinal axons. Of these, 79% (22/28) were excited by PAG stimulation, and 59% (10/17) were not immunoreactive for PNMT. Conversely, 42% (26/62) of RVLM presympathetic neurons were either unaffected or activated by CCK administration and had slower conduction velocities (1.4 +/- 0.3 m/sec) than cells inhibited by CCK. Fifty percent (11/22) of these cells were driven by PAG stimulation, and most (11/14 or 79%) were PNMT-positive. These results suggest that cardiovascular responses elicited by PAG stimulation occur via activation of non-C1 and C1 RVLM presympathetic neurons. RVLM neurons inhibited by CCK were more likely to be driven by PAG stimulation and may be a subset of neurons responsible for driving gastrointestinal sympathetic vasomotor tone. CCK-induced inhibition of a subpopulation of RVLM presympathetic neurons may be implicated in postprandial hyperemia and postprandial hypotension.
Sartor
Daniela M
DM
Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, Department of Medicine, University of Melbourne, Heidelberg 3084, Victoria, Australia.
Verberne
Anthony J M
AJ
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001710:Biotin / Q000031:analogs & derivatives*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
C093086:biotinamide; D001710:Biotin; D002766:Cholecystokinin; D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine