Modulation of gastric sensory and motor functions by nitrergic and alpha2-adrenergic agents in humans.
OBJECTIVE
Disturbed gastric accommodation and sensation contribute to postprandial symptoms in dyspepsia, but the controlling mechanisms are unclear. Nitrergic and alpha2-adrenergic modulation of gastric sensory and motor function were assessed in this study.


METHODS
Using a factorial design, we assessed drug effects on gastric sensation during isobaric distentions and fasting and postprandial gastric motor function in 32 healthy volunteers. Each participant received one treatment: placebo; 0.3 or 0.5 microgram. kg-1. min-1 intravenous nitroglycerin; 0.0125, 0.025, or 0.1 mg clonidine orally; or combined nitroglycerin plus clonidine. In 16 other healthy subjects, the effects of clonidine and placebo on gastric emptying of solids were evaluated using the 13C-octanoic acid breath test.


RESULTS
Clonidine and nitroglycerin increased gastric compliance, but normal postprandial accommodation was still observed despite the induced relaxation. Clonidine but not nitroglycerin reduced aggregate and pain perception averaged over four distention levels. There were no significant drug interactions. No dose effect of clonidine was observed on gastric emptying.


CONCLUSIONS
Clonidine relaxes the stomach and reduces gastric sensation without inhibiting accommodation or emptying. Nitroglycerin relaxes the stomach without altering perception. Studies of the effects of clonidine on these gastric functions and symptoms in disease are warranted.
Thumshirn
M
M
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
Camilleri
M
M
Choi
M G
MG
Zinsmeister
A R
AR
D000284:Administration, Oral; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure; D001944:Breath Tests; D002210:Caprylates / Q000493:pharmacokinetics; D002247:Carbon Isotopes; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D019518:Postprandial Period; D011674:Pulse; D012677:Sensation; D013270:Stomach / Q000294:innervation*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D002210:Caprylates; D002247:Carbon Isotopes; D005996:Nitroglycerin; D003000:Clonidine; C031492:octanoic acid