gastrins and Hypertension

Topics: Animals; Blood Pressure; Gastrins; Humans; Hypertension; Ion Transport; Kidney; Receptor, Angiotensin, Type 1; Receptors, Dopamine D1; Salt Tolerance; Signal Transduction; Sodium; Stomach

Somatostatin, under physiological conditions, is a regulator of thyroid stimulating hormone, growth hormone, pancreatic islet-cell hormones and gastrin. In pharmacological dosage, gastric acid output, splanchnic blood flow and plasma renin levels, are influenced. A possible therapeutic effect on increased growth hormone secretion, disturbances of carbohydrate metabolism, gastroenteropathies and renal hypertension, is discussed. The clinical application is limited by the short biological half-life of the substance and the unspecific action on several organs.

Topics: Acromegaly; Animals; Diabetes Mellitus; Diabetic Retinopathy; Gastric Juice; Gastrins; Growth Hormone; Humans; Hypertension; Islets of Langerhans; Pancreatitis; Renin; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Topics: Adrenal Cortex Hormones; Animals; Central Nervous System; Gastrins; Graves Disease; Histamine; Humans; Hypertension; Male; Peptic Ulcer; Psychophysiology; Psychosomatic Medicine; Rats; Research

Excess dietary salt is strongly correlated with cardiovascular disease, morbidity, and mortality. Conversely, potassium likely elicits favorable effects against cardiovascular disorders. Gastrin, which is produced by the G-cells of the stomach and duodenum, can increase renal sodium excretion and regulate blood pressure by acting on the cholecystokinin B receptor. The aim of our study was to assess the effects of altered salt and potassium supplementation on serum gastrin levels in humans. A total of 44 subjects (38-65 years old) were selected from a rural community in northern China. All subjects were sequentially maintained on a relatively low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for 7 days (18.0 g/day of NaCl), and then a high-salt diet supplemented with potassium for another 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). The high-salt intake significantly increased serum gastrin levels (15.3 ± 0.3 vs. 17.6 ± 0.3 pmol/L). This phenomenon was alleviated through potassium supplementation (17.6 ± 0.3 vs. 16.5 ± 0.4 pmol/L). Further analyses revealed that serum gastrin was positively correlated with 24 h urinary sodium excretion (

Topics: Blood Pressure; China; Diet; Dietary Supplements; Female; Gastrins; Humans; Hypertension; Male; Middle Aged; Potassium; Sodium; Sodium Chloride, Dietary

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c) and cardiovascular risk factors in type 2 diabetes.. Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements.. Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049 ± 17,659 vs 27,270 ± 32,004 pmol/l × min (p = 0.838). In the placebo group AUC for insulin decreased from 27,392 ± 14,348 pmol/l × min to 22,938 ± 11,936 pmol/l × min (p = 0.002). Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for gastrin. HbA(1c) increased from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.3 ± 0.8% (56 ± 6 mmol/mol) in the esomeprazole-treated group and from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.4 ± 0.8% (57 ± 6 mmol/mol) in the placebo group (n = 21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No change in BP was seen in the patients treated with esomeprazole.. Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Combined Modality Therapy; Denmark; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Gastrins; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Insulin; Insulin Secretion; Male; Middle Aged; Placebo Effect; Proton Pump Inhibitors; Risk Factors; Yogurt

The purpose of the study was to evaluate the effect of 6 weeks treatment with hydrochlorothiazide or propranolol on gastric acid and gastrin secretion in essential hypertension. The study was carried out in 10 patients receiving propranolol and 10 treated with hydrochlorothiazide. Acid and gastrin secretion were determined during histamine stimulation tests (Kay's test). Before the treatment the patients with essential hypertension were not significantly different from healthy controls with respect to acid secretion and gastrinemia profile after histamine stimulus. In both groups of patients no significant effect was observed of hypotensive treatment on basal acid output, but a significant inhibitory effect on gastrin secretion was noted. This effect was significantly greater in patients treated with propranolol than in the hydrochlorothiazide group. Moreover, in propranolol-treated patients a significant fall of histamine-induced acid secretion was found.

Topics: Adult; Antacids; Depression, Chemical; Female; Gastric Acid; Gastrins; Humans; Hydrochlorothiazide; Hypertension; Male; Propranolol

To investigate whether GRK4 regulates the phosphorylation and function of renal CCKBR.. GRK4 A142V transgenic mice were used as an animal model of enhanced GRK4 activity, and siRNA was used to silence the GRK4 gene to investigate the regulatory effect of GRK4 on CCKBR phosphorylation and function. Finally, the co-localization and co-connection of GRK4 and CCKBR in RPT cells were observed by laser confocal microscopy and immunoprecipitation to explore the mechanism of GRK4 regulating CCKBR.. Gastrin infusion significantly increased urinary flow and sodium excretion rates in GRK4 WT mice (. GRK4 participates in the development of hypertension by regulating the phosphorylation of renal CCKBR leading to impaired CCKBR function and water and sodium retention. Knockdown of GRK4 restored the function of CCKBR. The enhanced co-connection between GRK4 and CCKBR may be an important reason for the hyperphosphorylation of GRK4 and CCKBR involved in the pathogenesis of hypertension.

Topics: Adenosine Triphosphatases; Animals; Gastrins; Hypertension; Mice; Receptor, Cholecystokinin B; RNA, Small Interfering; Sodium

Hypertensive nephropathy (HN) is a common cause of end-stage renal disease with renal fibrosis; chronic kidney disease is associated with elevated serum gastrin. However, the relationship between gastrin and renal fibrosis in HN is still unknown. We, now, report that mice with angiotensin II (Ang II)-induced HN had increased renal cholecystokinin receptor B (CCKBR) expression. Knockout of CCKBR in mice aggravated, while long-term subcutaneous infusion of gastrin ameliorated the renal injury and interstitial fibrosis in HN and unilateral ureteral obstruction (UUO). The protective effects of gastrin on renal fibrosis can be independent of its regulation of blood pressure, because in UUO, gastrin decreased renal fibrosis without affecting blood pressure. Gastrin treatment decreased Ang II-induced renal tubule cell apoptosis, reversed Ang II-mediated inhibition of macrophage efferocytosis, and reduced renal inflammation. A screening of the regulatory factors of efferocytosis showed involvement of peroxisome proliferator-activated receptor α (PPAR-α). Knockdown of PPAR-α by shRNA blocked the anti-fibrotic effect of gastrin in vitro in mouse renal proximal tubule cells and macrophages. Immunofluorescence microscopy, Western blotting, luciferase reporter, and Cut&tag-qPCR analyses showed that CCKBR may be a transcription factor of PPAR-α, because gastrin treatment induced CCKBR translocation from cytosol to nucleus, binding to the PPAR-α promoter region, and increasing PPAR-α gene transcription. In conclusion, gastrin protects against HN by normalizing blood pressure, decreasing renal tubule cell apoptosis, and increasing macrophage efferocytosis. Gastrin-mediated CCKBR nuclear translocation may make it act as a transcription factor of PPAR-α, which is a novel signaling pathway. Gastrin may be a new potential drug for HN therapy.

Topics: Angiotensin II; Animals; Apoptosis; Fibrosis; Gastrins; Humans; Hypertension; Hypertension, Renal; Jurkat Cells; Kidney Tubules, Proximal; Mice; Mice, Knockout; Nephritis; Phagocytosis; PPAR alpha; Receptors, Cholecystokinin; RNA, Small Interfering; Signal Transduction; Ureteral Obstruction

Our group observed the first case of synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis (CAG), in the absence of Helicobacter pylori infection. Demographic, clinical, endoscopic, and pathologic data were abstracted from the electronic medical record at Mount Sinai Hospital from 2013 to 2015. The patient's anonymity was carefully protected, and informed consent was obtained for publication of protected health information. A 53-year-old woman with hypertension presented to Mount Sinai Hospital in June 2013 for a second opinion for management of gastric and duodenal NETs. After evaluation by gastroenterology and surgery, repeat upper endoscopy with ultrasound and fine-needle aspiration revealed multiple diminutive type I gastric NETs and 2 duodenal NETs, against a background of autoimmune CAG, with biopsy pathology negative for H. pylori. She subsequently underwent a transduodenal resection of the duodenal NETs, confirming low-grade, gastrin-positive, stage T2 duodenal NET. On routine follow-up over the next 2 years, clinical, radiographic, and endoscopic surveillance revealed no recurrent or metastatic gastric or duodenal disease. This first report of synchronous duodenal gastrinoma and gastric NET in the setting of autoimmune CAG can broaden our understanding of gastric NET pathophysiology.

Topics: Autoimmune Diseases; Chronic Disease; Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Hypertension; Middle Aged; Neuroendocrine Tumors; Stomach Neoplasms

Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (cholecystokinin B receptor [CCKBR]; CI-988) or a D1-like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats. The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT cells from Wistar-Kyoto but not spontaneously hypertensive rats, stimulation of either D1-like receptor or gastrin receptor inhibited Na(+)-K(+)-ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from Wistar-Kyoto and spontaneously hypertensive rats, CCKBR and D1 receptor coimmunoprecipitated, which was increased after stimulation of either D1 receptor or CCKBR in RPT cells from Wistar-Kyoto rats; stimulation of one receptor increased the RPT cell membrane expression of the other receptor, effects that were not observed in spontaneously hypertensive rats. These data suggest that there is a synergism between CCKBR and D1-like receptors to increase sodium excretion. An aberrant interaction between the renal CCK BR and D1-like receptors (eg, D1 receptor) may play a role in the pathogenesis of hypertension.

Topics: Animals; Benzazepines; Diuresis; Dopamine Agonists; Dopamine Antagonists; Fenoldopam; Gastrins; Hormone Antagonists; Hypertension; Indoles; Kidney; Meglumine; Natriuresis; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Dopamine D1

Gastrin is a peptide hormone, which acts not only to regulate gastric acid secretion, but also to exert physiological actions such as the regulation of sodium balance. From a case (n = 95)-control (n = 82) study in Fuyang People's Hospital, Anhui Province, China, we found that the fasting serum gastrin levels are similar in normotensive and hypertensive adults but increased to higher levels in the latter group than in the former group after a mixed meal. We suggest that gastrin is involved in the regulation of blood pressure, possibly via the regulation of sodium and water metabolism and/or renin-angiotensin-aldosterone system. However, the mechanism remains to be determined.

Topics: Adult; Aldosterone; Angiotensin II; Blood Pressure; Case-Control Studies; Fasting; Female; Gastrins; Humans; Hypertension; Male; Postprandial Period; Renin; Renin-Angiotensin System; Water-Electrolyte Balance

The KCNQ1 gene encodes a voltage-dependent potassium ion channel, and mutations in this gene are the most common cause of congenital long QT syndrome (LQTS). In the present study, we investigated the various phenotypic characteristics of vertigo 2 Jackson (C3H/HeJCrl-Kcnq1(vtg-2J)/J) mice with a Kcnq1 mutation. Both heterozygotes (vtg-2J/+) and homozygotes (vtg-2J/vtg-2J) showed prolonged QT intervals in electrocardiograms (ECGs) compared to C3H/HeJ control (+/+) mice. Furthermore, vtg-2J/vtg-2J mice showed gastric achlorhydria associated with elevation of their serum gastrin levels. The serum corticosterone levels were also significantly increased in vtg-2J/vtg-2J mice. In addition, vtg-2J/vtg-2J mice exhibited significantly higher blood pressure. These findings indicate that the Kcnq1 mutation in vtg-2J mice alters various physiological functions in the cardiac, gastric and adrenocortical systems, and suggest that vtg-2J mice may represent a useful model for studying Kcnq1 functions.

Topics: Achlorhydria; Animals; Corticosterone; Disease Models, Animal; Electrocardiography; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Genotype; Hypertension; KCNQ1 Potassium Channel; Long QT Syndrome; Male; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Mutation; Phenotype; Stomach

Essential hypertension is a complex disease with both genetic and environmental determinants. The effect of spontaneous hypertension on the distribution and occurrence of somatostatin-, gastrin- and serotonin-immunoreactive cells in the fundus and pylorus of the rat stomach was examined by immunohistochemistry. The animals were killed by decapitation at 4 and 16 weeks of age (5 control rats and 5 hypertensive rats). Endocrine cells generally increase in number in hypertensive rats as compared to control rats. However, the detailed responses of endocrine cells to hypertension depend on the cell type, region of gastric mucosa and age of animals. The present results suggest that hypertension has an influence on the intrinsic regulatory system by endocrine cells control in the rat stomach.

Topics: Age Factors; Animals; Enterochromaffin Cells; Eosine Yellowish-(YS); Gastrin-Secreting Cells; Gastrins; Hematoxylin; Hypertension; Immunohistochemistry; Male; Pyloric Antrum; Rats; Rats, Inbred SHR; Serotonin; Somatostatin; Somatostatin-Secreting Cells; Stomach

1. The cardiovascular actions of cholecystokinin and related peptides were investigated in the pithed rat. The receptors and the mechanisms involved in these experiments were characterized. 2. Sulphated cholecystokinin octapeptide (sCCK-8, 0.1-100 nmol kg-1, i.v.) elicited a dose-dependent bradycardia and increase in mean arterial blood pressure. Neither gastrin-17 nor pentagastrin had any effect at concentrations up to 100 nmol kg-1. 3. Both the pressor response and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1). The selective CCKB receptor antagonists, CI-988 (1 mumol kg-1) and L-365,260 (15 mumol kg-1) did not inhibit the effects of sCCK-8. 4. The pressor response induced with sCCK-8 was reduced by treatment with either phentolamine (3 mumol kg-1) or guanethidine (2 mumol kg-1) and was unaffected by treatment with propranolol, atropine or hexamethonium. The pressor response also persisted following bilateral adrenalectomy. 5. The bradycardia induced with sCCK-8 was unaffected by treatment with phentolamine, propranolol, guanethidine, atropine, hexamethonium or bilateral adrenalectomy. 6. The tetrapeptide of cholecystokinin (CCK-4) elicited a dose-dependent pressor response but did not induce bradycardia. The pressor response was unaffected by devazepide (50 nmol kg-1), L-365260 (15 mumol kg-1) or phentolamine (3 mumol kg-1). 7. In the pithed rat, sCCK-8 acted via CCKA receptors to increase arterial blood pressure indirectly, at least in part, through activation of alpha-adrenoceptors. The observed bradycardia was also mediated byCCKA receptors but possibly through a direct action on the heart.

Topics: Adrenalectomy; Adrenergic Agents; Animals; Benzodiazepinones; Blood Pressure; Bradycardia; Cholecystokinin; Decerebrate State; Devazepide; Dose-Response Relationship, Drug; Gastrins; Guanethidine; Heart Rate; Hormone Antagonists; Hormones; Hypertension; Indoles; Male; Meglumine; Pentagastrin; Phentolamine; Proglumide; Rats; Receptors, Cholecystokinin; Sincalide; Tetragastrin

Secretion of insulin, glucagon, gastrin and pancreatic polypeptide (PP) at basal and test meal stimulation conditions were investigated in 17 patients with essential hypertension (EH) before and after 12 months of treatment with prazosin and in 10 healthy subjects. Before prazosin therapy, patients with EH differ from healthy subject higher insulin and gastrin but lower PP secretion after test meal stimulation. 12 month therapy with prazosin enhanced insulin and suppressed gastrin secretion stimulated by test meal in comparison to the pretreatment values. Prazosin therapy did not influence significantly glucagon and PP secretion. Our results suggest, that long term prazosin treatment markedly influenced insulin and gastrin secretion in patients with EH.

Topics: Adolescent; Adult; Drug Administration Schedule; Female; Gastrins; Humans; Hypertension; Male; Middle Aged; Pancreatic Hormones; Prazosin; Reference Values

In 40 patients (pts) with essential hypertension (EH) the plasma levels of insulin, glucagon, gastrin and prolactin during 2 week therapy with nifedipine were evaluated. In pts with EH there were higher levels of hormones than in control subjects. During nifedipine therapy there was no elevation of the plasma hormone levels although the blood pressure was lowered. This study shows that there are other than hypertension factors in the pathogenesis of elevated hormone levels in EH.

Topics: Adult; Female; Gastrins; Glucagon; Humans; Hypertension; Insulin; Male; Middle Aged; Nifedipine; Prolactin

A group of 20 patients with primary hypertension (NT) were studied for the influence of six-week propranolol therapy on the secretion of immunoreactive insulin (IR-I), gastrin glucagon (IR-G) and pancreatic polypeptide (IR-PP) induced by a high-fat test meal. The results of the examination before the therapy were compared with examination of 10 healthy persons. Before the therapy, the patients with NT revealed a decreased reactivity of IR-PP to the food stimulus. After propranolol therapy, the authors found a significant change of glucagonemia profile and pancreatic polypeptide concentration induced by a test meal. The results of the examinations made suggest a direct or indirect participation of beta-adrenergic endings in the regulation of glucagon and pancreatic polypeptide secretion in patients with primary hypertension.

Topics: Adolescent; Adult; Female; Gastrins; Glucagon; Humans; Hypertension; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Hormones; Pancreatic Polypeptide; Propranolol

The largest-known family tree of a kindred with multiple endocrine neoplasia type I, dating back to 1840, has been constructed in Tasmania. There are over 600 descendants of one English migrant and his spouse living today. Preliminary data suggests that overall, one-quarter of all family members, and one-half of those above the age of 40 manifest one or more endocrine tumours. In the majority of cases, the diagnosis was not suspected until the general practitioner was informed of the family history, as the symptoms are vague, sometimes bizarre, and overlap with those of common disorders.

Topics: Adult; Aged; Child; Female; Gastrins; Humans; Hypercalcemia; Hypertension; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Prolactin

A case of hypergastrinemia, diarrhea, and relentless hypokalemia occurring in a middleaged, mildly hypertensive female is described. The presence of a gastrinoma was suggested by the additional findings of an inordinate degree of hypokalemia for the amount of thiazide used for the treatment of her hypertension; failure of her hypokalemia to correct itself with adequate doses of oral potassium that had previously corrected this problem; and amelioration of her symptoms and hypokalemia when she was treated with short-term oral potassium chloride and longterm cimetidine.

Topics: Diarrhea; Female; Gastrins; Humans; Hypertension; Hypokalemia; Middle Aged; Zollinger-Ellison Syndrome

The sympathetic nervous system is of major importance for the regulation of several physiologic functions. Drugs that inhibit the actions of catecholamines and adrenergic drugs are used in the treatment of many clinical disorders. The potential role of catecholamines in a number of human diseases has, however, until recent years been studied to a limited extent only due to lack of methods for quantitation of sympathetic nervous activity. After the development of enzymatic isotope-derivative assays, reliable measurements of noradrenaline and adrenaline became available. Studies in man have shown that plasma noradrenaline is an index of sympathetic nervous activity. The present survey deals with noradrenaline and adrenaline concentrations in blood, tissue, and cerebrospinal fluid in a number of clinical disorders viz. arterial hypertension, duodenal ulcer, malignant tumors, primary depressive illness, and ketotic hypoglycemia.

Topics: Adult; Blood Pressure; Child; Clonidine; Depression; Duodenal Ulcer; Epinephrine; Female; Gastrins; Heart Rate; Humans; Hypertension; Hypoglycemia; Ketosis; Male; Middle Aged; Neoplasms; Norepinephrine; Sympathetic Nervous System

In 37 patients with hypertension and/or renal disease, blood from a peripheral and a renal vein was drawn during renal vein catheterization. The serum gastrin concentrations were determined and found by paired comparison to be statistically significantly (p less than 0.05) higher in the peripheral than in the renal vein. A test meal was given to 9 male controls and 7 male azotemic patients, and the serum gastrin concentration response determined. The mean fasting serum gastrin values were 173 +/- 22 pg/ml in the group of patients versus 42 +/- 5.5 pg/ml in the controls. The serum gastrin response was significantly higher and of longer duration in the azotemic patients than in the controls. The pentagastrin-stimulated gastric acid secretion was, however, equal in the two groups.

Topics: Digestion; Eating; Fasting; Food; Gastric Juice; Gastrins; Humans; Hypertension; Male; Pentagastrin; Secretory Rate; Stimulation, Chemical; Uremia

Topics: Adult; Barium Sulfate; Gastrins; Hematemesis; Humans; Hyperparathyroidism; Hypertension; Laparotomy; Male; Methyldopa; Multiple Endocrine Neoplasia; Peptic Ulcer; Pituitary Diseases; Zollinger-Ellison Syndrome