Renal Effects of Adrenomedullin in the Rat

Vari, Richard C.; Adkins, Steven; Samson, Willis K.

doi:10.3181/00379727-211-43959

Cited by 82 publications

(61 citation statements)

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“…) are significantly larger than ADM doses shown previously to produce hemodynamic and natriuretic effects in rats and humans [1 to 6 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 (23,49)]. It remains to be determined whether blockade of endogenous ADM action affects food intake or gastric emptying.…”

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confidence: 99%

Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Reidelberger

Kelsey

Heimann

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Heimann. Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats. Am J Physiol Regulatory Integrative Comp Physiol 282: R1395-R1404, 2002. First published January 17, 2002 10.1152/ajpregu.00597. 2001.-We previously demonstrated that amylin inhibits food intake and gastric emptying in rats with half-maximal effective doses (ED 50s) of 8 and 3 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 78 and 60%, respectively. In this study of identical design, rats received intravenous infusions of salmon calcitonin (sCT), rat calcitonin (rCT), rat calcitonin gene-related peptide (rCGRP), and rat adrenomedullin (rADM) for 3 h at dark onset, and food intake was measured for 17 h or for 15 min and gastric emptying of saline was measured during the final 5 min. sCT, rCGRP, and rADM inhibited food intake with estimated ED50s of 0.5, 26, and 35 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 88, 90, and 49%, respectively. rCT was not effective at doses up to 100 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . sCT, rCGRP, rADM, and rCT inhibited gastric emptying with ED50s of 1, 130, 160, and 730 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 60, 66, 60, and 33%, respectively. These results suggest that amylin and sCT may act by a common mechanism to decrease food intake, which includes inhibition of gastric emptying.calcitonin; calcitonin gene-related peptide; adrenomedullin; anorexia; potency AMYLIN (ALSO CALLED ISLET amyloid polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreas in response to a meal (11, 51). Amylin has also been detected in gut endocrine cells (35), visceral sensory neurons (36), and throughout the brain (44). Exogenous amylin potently reduces food intake (1, 3, 39), body weight (1), adiposity (41), gastric emptying (10, 39), and gastric acid secretion (15) when administered systemically or into the brain. We recently demonstrated that the minimal effective intravenous dose for amylin-induced inhibition of food intake and gastric emptying in rats (1 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) increases plasma amylin by an amount comparable to that produced by a meal (3,39). We also demonstrated that in suppressing feeding and gastric emptying, amylin is at least as potent and efficacious as CCK (39), a physiological inhibitor of food intake and gastric emptying.These results support the hypothesis that amylin acts as a hormonal signal to the brain to inhibit gastric emptying and food intake and that amylin produces satiety, in part, through inhibition of gastric emptying.Calcitonin gene-related peptide (CGRP), calcitonin (CT), and adrenomedullin (ADM), together with amylin, form a family of structurally related peptides with overlapping biological actions (Fig. 1). Each of these peptides inhibits food intake (13,22,32,45) and gastric emptying (8,20,30,38) when administered systemically or into the brain. The teleost peptide salmon CT (sCT) appears to be significantly more potent than either amylin (29) or mammalian CTs (8, 29, 47) in decreasing food intake and gastric emp...

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confidence: 99%

Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Reidelberger

Kelsey

Heimann

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Adrenomedullin causes vasodilatation, 9 increases cardiac output, 10 and induces diuresis and natiuresis. 11 Conversely, the peripheral vasoconstrictor endothelin, adrenomedullin's counterpart, has anti-natriuretic and mitogenic properties. 12 Plasma levels of both peptides are elevated in HF and have been suggested to be of prognostic value.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department

Bahrmann¹,

Christ

Hofner

et al. 2016

European Heart Journal: Acute Cardiovascular Care

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Background: Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED. Methods: We consecutively enrolled 302 non-surgical patients ⩾70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models. Results: Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156-319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62-4.48) vs. 1.11 nmol/L (IQR 0.83-1.80), P<0.001 and 81 ng/L (IQR 38-340) vs. 17 ng/L (IQR 0.9-38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61-2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97-10.68, P=0.056). Conclusion: Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED.

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“…CGRP is a spliced variant of the calcitonin gene and this neuropeptide is present in perivascular sensory nerves (29). ADM, PAMP, and CGRP have vasodilator activity with different mechanisms of action (4,6,7,16,17,(27)(28)(29)35). ADM has been reported to relax vascular muscle in an endothelium-dependent manner in some vascular beds studied, and those responses are species or vascular bed dependent, whereas PAMP has modest activity and has been reported to inhibit norepinephrine release or decrease vascular resistance by a nitric oxide-independent mechanism (4-6, 17, 27, 28, 33-35).…”

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confidence: 99%

Responses to human CGRP, ADM, and PAMP in human thymic arteries

Champion

Bivalacqua

Pierce

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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. Responses to human CGRP, ADM, and PAMP in human thymic arteries. Am J Physiol Regul Integr Comp Physiol 284: R531-R537, 2003; 10.1152/ajpregu.00337.2002Responses to human CGRP, adrenomedullin (ADM), and proadrenomedullin NH2-terminal 20 peptide (PAMP) were studied in small human thymic arteries. CGRP, ADM, and PAMP produced concentrationdependent vasodilator responses in arteries preconstricted with the thromboxane mimic U-46619. Responses to ADM and PAMP were attenuated, whereas responses to CGRP were not altered by endothelial denudation. Inhibitors of nitric oxide synthase and guanylyl cyclase attenuated responses to ADM and PAMP but not to CGRP. The CGRP1 receptor antagonist CGRP(8-37) attenuated responses to CGRP and ADM but not to PAMP. Responses to CGRP were reduced by SQ-22536 and Rp-cAMPS, inhibitors of adenylyl cyclase and PKA. These data suggest that responses to CGRP and ADM are mediated by CGRP(8-37)-sensitive receptors and that the endothelial ADM receptor induces vasodilation by a nitric oxide-guanylyl cyclase mechanism, whereas a smooth muscle CGRP receptor signals by a cAMP-dependent mechanism. A different endothelial receptor recognizes PAMP and signals by a nitric oxide-dependent mechanism. CGRP1 receptor; vascular endothelium; vascular tone; human thymus ADRENOMEDULLIN (ADM) and proadrenomedullin NH 2 -terminal 20 peptide (PAMP) are distinct products encoded by the ADM gene (20-23). The human form of ADM consists of 52 amino acids and a six-membered ring structure that shares homology with CGRP and amylin (20)(21)(22)(23). PAMP consists of 20 amino acids and does not share the six-membered ring structure (20)(21)(22). ADM was discovered in human pheochromocytoma cells and has been localized in many tissues, including vascular smooth muscle cells and the endothelium (11,13,15,16,20). ADM plasma levels are increased in disorders, such as hypertension, heart and renal failure, and hypoxia, and ADM induces a different spectrum of hemodynamic effects than do nitrovasodilators (8, 12-14, 18, 23, 26, 35). PAMP is found in the NH 2 -terminal portion of the precursor for ADM and has a similar distribution, including vascular smooth muscle and the endothelium (17,20,24,36).

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Renal Effects of Adrenomedullin in the Rat

Cited by 82 publications

References 4 publications

Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department

Responses to human CGRP, ADM, and PAMP in human thymic arteries

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