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

Abstract

Gentilcore D, Little TJ, Feinle-Bisset C, Samsom M, Smout AJ, Horowitz M, Jones KL. Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects. Am J Physiol Gastrointest Liver Physiol 293: G692-G698, 2007. First published August 9, 2007; doi:10.1152/ajpgi.00199.2007.-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 ϭ 0 -60 min), followed by intraduodenal saline for a further 60 min (t ϭ 60 -120 min) on 2 days. Granisetron (10 g/kg) or control (saline) was given intravenously at t ϭ Ϫ25 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 Ͻ 0.0001 for all); granisetron had no effect on these responses. Granisetron suppressed the number and amplitude (P Ͻ 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 POSTPRANDIAL HYPOTENSION, defined as a fall in systolic blood pressure of Ն20 mmHg within 2 h of a meal that is sustained for at least 30 min, is now recognized as a major cause of morbidity and mortality (7, 16) by predisposing to a number of disorders, including syncope, transient ischemic attacks, stroke, and angina (16). Postprandial hypotension occurs more frequently than orthostatic hypotension (16), and those at greatest risk include the elderly and patients with autonomic dysfunction, the latter usually secondary to diabetes (16). Current treatment options are suboptimal.Several factors, including impaired regulation of splanchnic blood flow, the release of gastrointestinal hormones, and duodenal sympathetic nerve activity, have been identified as possible pathophysiological mechanisms in postprandial hypotension (16). The magnitude of the fall in blood pressure is dependent on meal composition; ingestion of carbohydrate, particularly glucose, has been reported to have the greatest suppressive effect on blood pressure (17). Th...

Effects of small intestinal glucose load on blood pressure, splanchnic blood flow, glycemia, and GLP-1 release in healthy older subjects

“…The effects of enteral glucose on blood pressure may potentially reflect the neurotransmitter 5-hydroxytryptamine (5-HT) (54). However, in healthy older individuals, the 5-HT3 antagonist granisetron in a dose of 10 g/kg, had no effect on the blood pressure and heart rate response to intraduodenal glucose (12). A role for intestinal taste receptors, which have been linked to GLP-1 release (19,53), warrants evaluation as is the case for the portal TRPv4 channel (35).…”

Glucose increases synaptic transmission from vagal afferent central nerve terminals via modulation of 5-HT3 receptors

“…Activation of 5-HT 3 receptors may also play a critical role in gastrointestinal function. Gastric emptying is delayed by 5-HT 3 receptor selective agonists via relaxation of the proximal stomach (16,31), whereas receptor selective antagonists accelerate gastric transit (25,56,76). Indeed, 5-HT 3 antagonists have been used clinically to treat the gastroparesis associated with diabetes (45).…”

Plasticity of vagal brainstem circuits in the control of gastrointestinal function

“…Alternatively, glucose acting at multiple sites could amplify peripheral signals to produce a rapid and robust response in motor output. Gastric relaxation and a delay in gastric emptying result from glucose within the intestinal tract (Gentilcore et al , 2007;Rayner et al , 2001) so vagal afferent activation by glucose is likely to cause an inhibitory efferent motor response.…”