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NEUROREGULATION AND MOTILITY

Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects

¹University of Adelaide, Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia, and ²Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands

Submitted 4 May 2007 ; accepted in final form 23 July 2007

Postprandial hypotension is an important clinical problem, particularly in the elderly. 5-Hydroxytryptamine₃ (5-HT₃) mechanisms may be important in the regulation of splanchnic blood flow and blood pressure (BP), and in mediating the effects of small intestinal nutrients on gastrointestinal motility. The aims of this study were to evaluate the effects of the 5-HT₃ antagonist granisetron on the BP, heart rate (HR), and antropyloroduodenal (APD) motility responses to intraduodenal glucose in healthy older subjects. Ten subjects (5 male, 5 female, aged 65–76 yr) received an intraduodenal glucose infusion (3 kcal/min) for 60 min (t = 0–60 min), followed by intraduodenal saline for a further 60 min (t = 60–120 min) on 2 days. Granisetron (10 µg/kg) or control (saline) was given intravenously at t = –25 min. BP (systolic and diastolic), HR, and APD pressures were measured. Pressure waves in the duodenal channel closest ("local") to the infusion site were quantified separately. During intraduodenal glucose, there were falls in systolic and diastolic BP and a rise in HR (P < 0.0001 for all); granisetron had no effect on these responses. Granisetron suppressed the number and amplitude (P < 0.05 for both) of local duodenal pressures during intraduodenal glucose. Otherwise, the effects of intraduodenal glucose on APD motility did not differ between study days. We conclude that in healthy older subjects, 5-HT₃ mechanisms modulate the local duodenal motor effects of, but not the cardiovascular responses to, small intestinal glucose.

heart rate; 5-hydroxytryptamine₃; granisetron; intraduodenal glucose; antropyloroduodenal motility

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