Effects of Intraduodenal Glucose Concentration on Blood Pressure and Heart Rate in Healthy Older Subjects

American Journal of Physiology-Gastrointestinal and Liver Physi

Little²,

Feinle‐Bisset³

et al. 2007

Self Cite

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...

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

American Journal of Physiology-Gastrointestinal and Liver Physi

Little²,

Feinle‐Bisset³

et al. 2007

Self Cite

“…and/or spinal reflex mechanisms. The effects of gastric distension on sympathetic nerve activity in response to water drinking may be related to stretch (44) and osmolarity (38), although the hypotensive response to intraduodenal glucose is apparently independent of osmolarity (8). In mice, recent evidence suggests that the rise in blood pressure induced by water ingestion is mediated via osmoreceptive afferent nerves in the portal tract through transient receptor potential vanilloid 4 channel activation (23,29).…”

Section: Discussionmentioning

confidence: 99%

Effects of variations in intragastric volume on blood pressure and splanchnic blood flow during intraduodenal glucose infusion in healthy older subjects

Vanis

American Journal of Physiology-Regulatory, Integrative and Comp

Lange

et al. 2012

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(BP) is triggered by the interaction of nutrients with the small intestine and associated with an increase in splanchnic blood flow. Gastric distension may attenuate the postprandial fall in BP. The aim of this study was to determine the effects of differences in intragastric volume, including distension at a low (100 ml) volume, on BP and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in healthy older subjects. BP and heart rate (HR; automated device), SMA blood flow (Doppler ultrasound), mesenteric vascular resistance (MVR), and plasma norepinephrine of nine male subjects (65-75 yr old) were measured after an overnight fast on 4 separate days in random order. On each day, subjects were intubated with a nasoduodenal catheter, incorporating a duodenal infusion port, and orally with a second catheter, incorporating a barostat bag, positioned in the fundus. Each subject received a 60-min (t ϭ 0 -60 min) intraduodenal glucose infusion (3 kcal/min) and gastric distension at a volume of 1) 0 ml (V0), 2) 100 ml (V100), 3) 300 ml (V300), or 4) 500 ml (V500). Systolic BP fell (P Ͻ 0.05) during V0, but not during V100, V300, or V500. In contrast, HR (P Ͻ 0.01) and SMA blood flow (P Ͻ 0.001) increased and MVR decreased (P Ͻ 0.05) comparably on all 4 days. Plasma norepinephrine rose (P Ͻ 0.01) in response to intraduodenal glucose, with no difference between the four treatments. There was a relationship between the areas under the curve for the change in systolic BP from baseline with intragastric volume (r ϭ 0.60, P Ͻ 0.001). In conclusion, low-volume (Յ100 ml) gastric distension has the capacity to abolish the fall in BP induced by intraduodenal glucose in healthy older subjects without affecting SMA blood flow or MVR. These observations support the concept that nonnutrient gastric distension prior to a meal has potential therapeutic applications in the management of postprandial hypotension.barostat; distension; postprandial hypotension POSTPRANDIAL HYPOTENSION is an important clinical problem, particularly in the elderly (17,27). It is distinct from, and may occur more frequently than, orthostatic hypotension and represents a substantial cause of morbidity and mortality (17). While the mechanisms underlying postprandial hypotension are poorly defined, several interrelated factors, including meal composition, gastric distension, the rate of small intestinal nutrient delivery, changes in splanchnic blood flow, and neural and hormonal mechanisms, have been identified (17, 39). In the elderly, it is likely that "normality" and postprandial hypotension represent a continuum, as is the case with many age-related phenomena. For example, after an oral glucose load, systolic blood pressure predictably falls in healthy older, but not young, subjects, and in the elderly the magnitude of this decrease is variable (18).Our previous studies established that, in healthy older subjects and patients with type 2 diabetes, the magnitude of the fall in blood pressure in response to enteral glucose is depend...

“…patients with type 2 diabetes (28,46) have established that there is a direct relationship between the magnitude of the fall in systolic blood pressure with the rate of small intestinal delivery of glucose (26,28,41,42), a response that depends on the total load of glucose entering the duodenum independent of glucose concentration (11,27). When glucose enters the small intestine, it inhibits gastric emptying in a load-dependent fashion, so that glucose entry is sustained at ϳ3 kcal/min (21,22).…”

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confidence: 99%

Comparative effects of oral and intraduodenal glucose on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects

American Journal of Physiology-Regulatory, Integrative and Comp

Nair²,

Vanis³

et al. 2009

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Gentilcore D, Nair NS, Vanis L, Rayner CK, Meyer JH, Hausken T, Horowitz M, Jones KL. Comparative effects of oral and intraduodenal glucose on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects. Am J Physiol Regul Integr Comp Physiol 297: R716 -R722, 2009. First published June 24, 2009 doi:10.1152/ajpregu.00215.2009.-Postprandial hypotension occurs frequently, particularly in the elderly. The magnitude of the fall in blood pressure (BP) and rise in heart rate (HR) in response to enteral glucose are greater when gastric emptying (GE) or small intestinal infusion are more rapid. Meal ingestion is associated with an increase in splanchnic blood flow. In contrast, gastric distension may attenuate the postprandial fall in BP. The aims of this study were to evaluate, in older subjects, the comparative effects of intraduodenal glucose infusion, at a rate similar to GE of oral glucose, on BP, HR, superior mesenteric artery (SMA) flow, and blood glucose. Eight healthy subjects (5 men, 3 women, age 66 -75 yr) were studied on two occasions. On day 1, each subject ingested 300 ml of water containing 75 g glucose. GE was quantified by three-dimensional ultrasonography between time t ϭ 0 -120 min, and the rate of emptying (kcal/min) was calculated. On day 2, glucose was infused intraduodenally at the same rate as that on day 1. On both days, BP, HR, SMA flow, and blood glucose were measured. The mean GE of oral glucose was 1.3 Ϯ 0.1 kcal/min. Systolic BP (P Ͻ 0.01), SMA flow (P Ͻ 0.05), and blood glucose (P Ͻ 0.01) were greater and HR less (P Ͻ 0.01) after oral, compared with intraduodenal, glucose. There were comparable falls in diastolic BP during the study days (P Ͻ 0.01 for both). We conclude that the magnitude of the fall in systolic BP and rise in HR are less after oral, compared with intraduodenal, glucose, presumably reflecting the "protective" effect of gastric distension. postprandial hypotension; gastric emptying; three-dimensional and Doppler ultrasound POSTPRANDIAL HYPOTENSION, defined as a decrease in systolic blood pressure Ն20 mmHg, occurring within 2 h of the end of a meal (23,25,38,39), is an important clinical problem, most commonly affecting the elderly and patients with autonomic dysfunction, the latter often secondary to diabetes (23,25,38,39). Postprandial hypotension is associated with significant complications, including syncope and falls (25) and, in some cases, stroke and angina (1,25,51).The stomach is likely to modulate the hypotensive response to a high-carbohydrate meal in two ways, first, by controlling the rate at which glucose enters the small intestine. Our laboratory's studies in healthy older subjects (26, 42) and patients with type 2 diabetes (28, 46) have established that there is a direct relationship between the magnitude of the fall in systolic blood pressure with the rate of small intestinal delivery of glucose (26,28,41,42), a response that depends on the total load of glucose entering the duodenum independent of glucose concentration (11,27). When glu...