Role of glucagon in splanchnic hyperemia of chronic portal hypertension

Benoit, Joseph N.; Zimmerman, Ben G.; Premen, A. J.; Go, V.L.W.; Granger, D. Neil

doi:10.1152/ajpgi.1986.251.5.g674

Cited by 74 publications

(44 citation statements)

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“…Serum glucagon levels were significantly correlated with high systemic vascular resistance index (r = -0.523; P = 0) and HVPG (r = 0.34; P = 0.019). Glucagon significantly increases portal pressure [157][158][159] , and causes splanchnic vasodilation [148] . Geraghty et al [158] found a strong correlation between portal pressure and glucagon levels (r = 0.85).…”

Section: Angiogenesismentioning

confidence: 99%

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

Gjeorgjievski¹

2016

WJH

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AIM:To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS:Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS:PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepaticportosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. SYSTEMA...

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Section: Angiogenesismentioning

confidence: 99%

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

Gjeorgjievski¹

2016

WJH

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“…It has been suggested that vasoconstriction is indirectly caused by an inhibited release of vasodilative pancreatic and gut peptides. Among insulin [15], VIP [16], substance P [17]and others, glucagon has a vasodilative effect on the mesenteric vascular bed and has been proposed as one regulator of mesenteric and portal blood flow [18, 19, 20]. The release of glucagon from the pancreatic α-cell is under the inhibitory control of somatostatin and its analogues [18, 21].…”

Section: Introductionmentioning

confidence: 99%

Effects of Different Octreotide Dosages on Splanchnic Hemodynamics and Glucagon in Healthy Volunteers

Sartipy

Brensing²,

Göke³

et al. 1999

Digestion

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Aims: This study evaluated the dependence of portal and mesenteric blood flow and plasma glucagon levels on octreotide dosage and its mode of application. Methods: Two groups of 10 individuals each received octreotide either subcutaneously (placebo, 100 and 200 µg) or intravenously (100-µg bolus i.v., 25 and 100 µg/h) in a double-blind, random order. Using Doppler ultrasound, we examined portal and mesenteric blood flow and measured plasma glucagon levels at regular intervals within a 4-hour period under fasting conditions. Results: Contrary to placebo, octreotide caused a decrease in portal blood flow (PVF) and in superior mesenteric artery blood flow (SMAF) together with an increase in the mesenteric pulsatility index (PI). The same total dose of 100 µg octreotide caused a similar PVF response, averaged over 4 h, given either subcutaneously (–28.0 ± 4.8%), intravenously (–29.4 ± 4.3%) or as a continuous infusion (–29.3 ± 4.6%). As concerns intravenous infusions, 100 µg/h was more effective than 25 µg/h (–37.8 ± 6.2 vs. –29.3 ± 4.6%). The PVF reduction remained constant during intravenous infusion, whereas glucagon levels decreased progressively over the entire observation time. Conclusions: The decrease in PVF is dependent on the octreotide dose. However, this is not constantly paralleled by a decrease in plasma glucagon concentration.

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“…5,6 Other studies have shown an increased splanchnic production of carbon monoxide in portal hypertension 7 as well as an increased release of splanchnic vasodilatory peptides, such as glucagon. 8,9 Vasoconstrictor systems are also up-regulated, probably as a counter-regulatory response to the hyperdynamic state. 10 Sympathetic nervous and renin-angiotensin aldosterone systems are enhanced, and the plasma levels of vasopressin and endothelin-1 are elevated.…”

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confidence: 99%

Left Ventricular Hypertrophy in Rats With Biliary Cirrhosis

et al. 2003

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Portal hypertension induces neuroendocrine activation and a hyperkinetic circulation state. This study investigated the consequences of portal hypertension on heart structure and function. Intrahepatic portal hypertension was induced in male Sprague-Dawley rats by chronic bile duct ligation (CBDL). Six weeks later, CBDL rats showed higher plasma angiotensin-II and endothelin-1 (P < .01), 56% reduction in peripheral resistance and 73% reduction in pulmonary resistance (P < .01), 87% increase in cardiac index and 30% increase in heart weight (P < .01), and increased myocardial nitric oxide (NO) synthesis. In CBDL rats, macroscopic analysis demonstrated a 30% (P < .01) increase in cross-sectional area of the left ventricular (LV) wall without changes in the LV cavity or in the right ventricle (RV). Histomorphometric analysis revealed increased cell width (12%, P < .01) of cardiomyocytes from the LV of CBDL rats, but no differences in myocardial collagen content. Myocytes isolated from the LV were wider (12%) and longer (8%) than right ventricular myocytes (P < .01) in CBDL rats but not in controls. CBDL rats showed an increased expression of ANF and CK-B genes (P < .01). Isolated perfused CBDL hearts showed pressure/end-diastolic pressure curves and response to isoproterenol identical to sham hearts, although generated wall tension was reduced because of the increased wall thickness. Coronary resistance was markedly reduced. This reduction was abolished by inhibition of NO synthesis with N-nitro-L-arginine. Expression of eNOS was increased in CBDL hearts. In conclusion, portal hypertension associated to biliary cirrhosis induces marked LV hypertrophy and increased myocardial NO synthesis without detectable fibrosis or functional impairment. This observation could be relevant to patients with cirrhosis. (HEPATOLOGY 2003;38:589-598.) H yperdynamic circulation is a common feature in human and experimental portal hypertension, with or without cirrhosis. This is also called hyperdynamic circulatory syndrome and is the consequence of splanchnic and systemic vasodilatation, manifested by increased heart rate, cardiac output, and regional blood flow with decreased mean arterial pressure and systemic vascular resistance (SVR). 1 The mechanism of systemic and splanchnic vasodilatation is multifactorial. Many studies have suggested a prominent role for increased biosynthesis of nitric oxide (NO), 2 which is due to increased endothelial nitric oxide synthase (eNOS) activity. 3,4 It has been shown that NO inhibition attenuates the hyperdynamic circulation observed in portal hypertensive rats. 5,6 Other studies have shown an increased splanchnic production of carbon monoxide in portal hypertension 7 as well as an increased release of splanchnic vasodilatory peptides, such as glucagon. 8,9 Vasoconstrictor systems are also up-regulated, probably as a counter-regulatory response to the hyperdynamic state. 10 Sympathetic nervous and renin-angiotensin aldosterone systems are enhanced, and the plasma levels of vasopressin and endot...

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Role of glucagon in splanchnic hyperemia of chronic portal hypertension

Cited by 74 publications

References 0 publications

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

Effects of Different Octreotide Dosages on Splanchnic Hemodynamics and Glucagon in Healthy Volunteers

Left Ventricular Hypertrophy in Rats With Biliary Cirrhosis

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