Pituitary responsiveness to 44 amino acid human pancreatic growth hormone releasing factor was tested under conditions of euglycaemia and hyperglycaemia in six normal subjects. A 100 micrograms dose of growth hormone releasing factor was given at a fasting blood glucose of 5.1 +/- 0.4 mmols/l (mean +/- S.D.), and at a blood glucose level of 10.9 +/- 1.5. Under conditions of hyperglycaemia, the GH response to releasing factor was significantly depressed when compared to results obtained at fasting blood glucose (n = 6, t = 3.902, P = 0.0114). This is in keeping with the hypothesis that hyperglycaemia, mediated by the hypothalamus, causes decreased pituitary sensitivity to natural growth hormone releasing hormone.
Global abdominal visceral ischemia leads to profound cardiovascular reflex adjustments. However, the separate contributions of the celiac artery and superior mesenteric artery (SMA) vascular beds to this reflex are unknown. Accordingly, we compared the effects of single and combined occlusions of these vessels on blood pressure (BP) in anesthetized cats. Tissue mass and pH of selected organs, regional blood gases, pH, and lactate also were measured as potential contributing factors. Occlusion of the SMA or celiac artery produced significantly (P < 0.05) different increments in BP (30 +/- 4 vs. 18 +/- 4 mmHg, respectively). Combined occlusion of the two vessels augmented BP by 53 +/- 12 mmHg, a significantly greater increase than during celiac ligation. Venous lactate levels increased significantly during SMA, but not celiac, occlusion, and the decline in venous pH was significantly greater in the SMA than in the celiac vascular bed (-0.20 +/- 0.03 vs. -0.08 +/- 0.02 pH units, P < 0.05, respectively). The decline in tissue pH of SMA-perfused organs during SMA occlusion was significantly greater than in celiac-perfused organs during celiac occlusion. Conversely, tissue mass subserved by the celiac artery was significantly greater than that subserved by the SMA (182 +/- 27 vs. 131 +/- 17 g, respectively). These data suggest that the larger cardiovascular reflex produced by SMA occlusion compared with celiac occlusion may be related to a greater increase of lactic acid concentration in tissue supplied by the SMA. In addition, the large reflex increase in BP produced by combined occlusion of these vessels is an additive effect, presumably related to larger organ mass and recruitment of more sensory nerve fibers.
Adenosine can induce visceral hyperalgesia and decrease oesophageal distensibility in humans. These evoked sensorimotor changes are similar to those described in patients with functional oesophageal (non-cardiac) chest pain. Thus, adenosine modulates oesophageal sensorimotor function and may play a role in the pathogenesis of functional chest pain.
Ischemically sensitive visceral sympathetic nerve fibers, which are thought to represent the afferent limb of a strong cardiovascular pressor reflex, can be stimulated by exogenously applied bradykinin (BK). During ischemia, BK also is known to be produced locally and to serve as an endogenous stimulus for activation of ischemically sensitive nerve endings. It is unclear, however, whether ischemically induced BK production is sufficient to elicit a reflex cardiovascular response. Accordingly, femoral arterial and venous catheters were positioned in anesthetized cats, and the superior mesenteric and celiac arteries were isolated for placement of snare occluders. After dual occlusion of these arteries (20 min), one of two chemically dissimilar specific kinin B2(BK2) receptor antagonists, HOE-140 (30–40 μg/kg iv, n = 8) or NPC-17731 (30–40 μg/kg iv, n= 11), was administered and dual occlusion was repeated. The reflex rise of mean arterial blood pressure (BP) of 16 ± 3.7% was significantly ( P < 0.05) reduced by HOE-140 to 8.4 ± 2.0%. NPC-17731 similarly attenuated the reflex BP increment from 13 ± 1.2 to 6.2 ± 1.6% ( P < 0.05). In a separate set of control animals the first and second periods of ischemia induced reflex BP increments that did not differ significantly (16 ± 2.7 and 16 ± 5.7%, respectively). Qualitatively similar decrements of the BP response were produced by the BK2 receptor antagonists in two additional groups in which blood flow to the superior mesenteric and celiac arteries was diverted to a venous reservoir to eliminate the initial transient (mechanically induced) rise in BP associated with artery ligation that is known not to be associated with the reflex response. These results indicate that the stimulation of BK2 receptors on visceral afferent nerves by BK is responsible, at least in part, for the reflex cardiovascular response during visceral ischemia.
Background Esophageal sensation is commonly assessed by barostat-assisted balloon distension (BBD) or dynamic balloon distension (DBD) technique, but their relative merits are unknown. Our aim was to compare the usefulness and tolerability of both techniques. Methods Sixteen healthy volunteers (M/F= 6/10) randomly underwent graded esophageal balloon distensions, using either BBD (n=8) or DBD (n=8). BBD was performed by placing a 5 cm long highly compliant balloon attached to a barostat, and DBD by placing a 5 cm long balloon attached to a leveling container. Intermittent phasic balloon distensions were performed in increments of 6 mm Hg. Sensory thresholds and biomechanical properties were assessed and compared. Key Results Sensory thresholds for first perception (mean ± SD; 21 ± 6 vs. 21.2 ± 5, mm Hg, p=0.9), discomfort (38 ± 8 vs. 35 ± 9, p=0.5), and pain (44 ± 4 vs. 45 ± 3, p=0.7) were similar with BBD and DBD techniques. However, more subjects tolerated DBD (7/8, 88%) when compared to BBD (4/8, 50 %). Forceful expulsion of balloon into stomach (n=4), pulling around the mouth (n=4), chest discomfort (n=2) and retching (n=2) were overlapping reasons for intolerance with BBD. Esophageal wall distensibility was similar with both techniques. Conclusions Both techniques provided comparable data on biomechanical properties. However, DBD was better tolerated than BBD for evaluation of esophageal sensation. Hence, we recommend DBD for performing esophageal balloon distension test.
Abdominal ischemia induces a pressor reflex caused mainly by C-fiber afferent stimulation. Because excitatory amino acids, such as glutamate, bind to N-methyl-D-aspartate (NMDA) and non-NMDA [dl-␣-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)] receptors and serve as important spinal neurotransmitters, we hypothesized that both receptors play a role in the abdominal ischemia pressor reflex. In chloralose-anesthetized cats, NMDA receptor blockade with 25.0 mM dl-2-amino-5-phosphonopentanoate did not alter the pressor reflex (33 Ϯ 9 to 33 Ϯ 7 mmHg, P Ͼ 0.05, n ϭ 4), whereas AMPA receptor blockade with 4.0 mM 6-nitro-7-sulfamylbenzo(f)quinoxaline-2,3-dione significantly attenuated the reflex (29 Ϯ 5 to 16 Ϯ 4 mmHg, P Ͻ 0.05, n ϭ 6). Because several studies suggest that anesthesia masks the effects of glutamatergic receptors, this experiment was repeated on decerebrate cats, and in this group, NMDA receptor blockade with 25.0 mM dl-2-amino-5-phosphonopentanoate significantly altered the pressor reflex (36 Ϯ 3 to 25 Ϯ 4 mmHg, P Ͻ 0.05, n ϭ 5). Our combined data suggest that spinal NMDA and AMPA receptors play a role in the abdominal ischemia pressor reflex.6-nitro-7-sulfamylbenzo(f)quinoxaline-2,3-dione; dl-2-amino-5-phosphonopentanoate; ␣-chloralose; decerebrate ACTIVATION OF CHEMOSENSITIVE C-fibers and, to a lesser extent, mechanosensitive A-␦ fibers in the abdominal visceral region causes large cardiovascular reflex responses. The blood pressure response to abdominal ischemia is bimodal. There is a rapid shift in blood volume evoked by occlusion of the celiac and superior mesenteric arteries that accounts for the initial, rapid, and transient increase in blood pressure (13,17,38,39). A reflex evoked by visceral ischemia accounts for the second, and more prolonged, increase in blood pressure (33, 39). Our previous studies have shown that interruption of blood flow to visceral organs during abdominal ischemia causes the production of endogenous metabolites such as bradykinin (5, 21, 30), histamine (12), leukotrienes (22), prostaglandins (6), protons (37), reactive oxygen species (36, 38), serotonin (11, 21), and substance P (21, 28), which, in turn, stimulate abdominal C-fiber afferent nerve endings. The axonal terminals of these afferent fibers synapse in the dorsal horn of the spinal cord onto neurons that project through interneurons to cardiovascular regions of the medulla. From these medullary neurons, projections extend to sympathetic preganglionic cell bodies, the activation of which ultimately stimulates efferent nerves innervating the heart and blood vessels. Thus stimulation of abdominal visceral afferent fibers evokes reflex increases in blood pressure through alterations in cardiac contractility, heart rate, and peripheral vasoconstriction. A number of studies from our laboratory have examined the role of various endogenous metabolites (and the receptors that bind to them) in the activation of visceral afferent nerves during the abdominal ischemia pressor reflex (5,6,11,12,21,22,28,30,(36)(37)(38)...
Prostaglandin concentrations are elevated in intestinal lymph during brief abdominal visceral ischemia, and exogenously applied prostaglandins can directly stimulate or sensitize ischemically sensitive visceral sympathetic nerve fibers. However, it is not known if prostaglandin production during abdominal ischemia is sufficient to contribute to the reflex cardiovascular response (e.g., hypertension). Accordingly, in anesthetized cats, the femoral artery was cannulated for measurement of arterial blood pressure, and the superior mesenteric and celiac arteries were isolated and fitted with snare occluders. After dual occlusion of these arteries (=20 min), the cyclooxygenase inhibitors indomethacin (10-20 mg/kg iv, n = 5, group 1) or acetylsalicylic acid [50 mg/kg iv (n = 6) and ia (n = 2); group 2] were administered and ischemia was repeated. In group 1, indomethacin lowered the reflex arterial blood pressure increment by 39% from 31 +/- 7 to 19 +/- 5 mmHg (P > 0.05). In group 2, acetylsalicylic acid significantly (P < 0.05) reduced the reflex rise in blood pressure by 46% (28 +/- 3 to 15 +/- 4 mmHg). A second, more invasive preparation (group 3) was utilized to 1) minimize the confounding, transient, nonreflex rise in blood pressure associated with arterial ligation, and 2) further assess the inhibitory effect of indomethacin. In group 3, the ischemia-induced blood pressure rise of 28 +/- 6 mmHg was reduced by 43% to 16 +/- 4 mmHg after indomethacin (n = 4, P < 0.05). Thus blockade of the cyclooxygenase pathway by two structurally dissimilar inhibitors attenuated the visceral-cardiovascular reflex response to brief ischemia, suggesting that prostaglandins released during visceral ischemia contribute significantly to the activation of the reflex cardiovascular response.
Functional chest pain is a common, yet poorly understood entity. The focus of this review is to explore the evolving research and clinical approaches with a particular emphasis on the sensory or afferent neuronal dysfunction of the esophagus as a key player in the manifestation of this pain syndrome. Although once regarded as a psychologic or esophageal motility disorder, recent advances have shown that many of these patients have visceral hyperalgesia. Whether visceral hypersensitivity is a central or peripheral perturbation of the gut-brain axis remains debatable. Response to empirical therapy with high-dose proton pump inhibitors, upper endoscopy, or prolonged recording of esophageal pH may identify gastroesophageal reflux disease as a source of chest pain. Esophageal balloon distension study can serve as a useful test for identifying hypersensitivity. Newer techniques, including functional magnetic resonance imaging, magnetoencephalogram, and cortical evoked potentials, are being investigated. High doses of proton pump inhibitors and low doses of tricyclic antidepressants or trazadone remain the mainstay of therapy, although several new approaches including theophylline have been shown to be beneficial.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.