Cholecystokinin selectively affects presympathetic vasomotor neurons and sympathetic vasomotor outflow.
Cholecystokinin (CCK) is a potential mediator of gastrointestinal vasodilatation during digestion. To determine whether CCK influences sympathetic vasomotor function, we examined the effect of systemic CCK administration on mean arterial blood pressure (MAP), heart rate (HR), lumbar sympathetic nerve discharge (LSND), splanchnic sympathetic nerve discharge (SSND), and the discharge of presympathetic neurons of the rostral ventrolateral medulla (RVLM) in alpha-chloralose-anesthetized rats. CCK (1-8 microg/kg iv) reduced MAP, HR, and SSND and transiently increased LSND. Vagotomy abolished the effects of CCK on MAP and SSND as did the CCK-A receptor antagonist devazepide (0.5 mg/kg iv). The bradycardic effect of CCK was unaltered by vagotomy but abolished by devazepide. CCK increased superior mesenteric arterial conductance but did not alter iliac conductance. CCK inhibited a subpopulation (approximately 49%) of RVLM presympathetic neurons whereas approximately 28% of neurons tested were activated by CCK. The effects of CCK on RVLM neuronal discharge were blocked by devazepide. RVLM neurons inhibited by exogenous CCK acting via CCK-A receptors on vagal afferents may control sympathetic vasomotor outflow to the gastrointestinal tract vasculature.
Sartor
Daniela M
DM
Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia.
Verberne
Anthony J M
AJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D004064:Digestive System / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D013153:Splanchnic Nerves / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology / Q000601:surgery
D006727:Hormone Antagonists; D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C410885:cholecystokinin 8; D002766:Cholecystokinin; D020109:Devazepide