Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A marked increase in adrenomedullin (AM) concentration was observed in rat plasma collected after intravenous infusion of lipopolysaccharide (LPS). Plasma immunoreactive (ir-) AM concentration increased already after 1 h exposure to 5 mg/kg of LPS and was elevated to 49.7 +/- 2.3 fmol/ml (mean +/- SEM) at 3 h after injection in contrast to 2.7 +/- 0.3 fmol/ml in saline-injected control rats. Plasma ir-AM level increased in a dose-dependent manner in a range of 0.008 to 5.0 mg/kg of LPS. AM gene transcription in LPS-injected rats was augmented more than 3-fold in ileum, liver, lung, aorta, and 2.4-fold even in skeletal muscle, in which AM was not thought to be produced in myocytes. These results, along with our recent data that AM production in cultured vascular smooth muscle cells (VSMCs) is stimulated with LPS, indicate that AM production is highly augmented in blood vessel, lung and intestine by administration of LPS. Since VSMCs express AM-specific receptors, secreted AM is deduced to actually exert a vasorelaxant effect especially in the endotoxin shock.
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PMID:Endotoxin markedly elevates plasma concentration and gene transcription of adrenomedullin in rat. 748 88

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P < .05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P < .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.
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PMID:Mechanisms of adrenomedullin-induced vasodilation in the rat kidney. 772 34

Adrenomedullin is a potent vasodilator peptide that was isolated from human pheochromocytoma. But the presence of adrenomedullin in the brain has not been clarified. We studied the presence of adrenomedullin in the human brain obtained at autopsy from 6 subjects by radioimmunoassay, as well as in the human adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma. Immunoreactive adrenomedullin was detected in every region of human brain examined (0.26-1.4 pmol/g wet weight) with the highest concentrations found in thalamus (1.40 +/- 0.39 pmol/g wet weight, mean +/- SEM) and hypothalamus (1.28 +/- 0.48 pmol/g wet weight). Reverse phase high performance liquid chromatography showed that the immunoreactive adrenomedullin in the human brain was eluted in the position of synthetic human adrenomedullin 1-52. High concentrations of immunoreactive adrenomedullin were found in human adrenal glands (12.6 +/- 1.0 pmol/g wet weight, n = 7), pheochromocytoma (4.5 +/- 1.5 pmol/g wet weight, n = 11), ganglioneuroblastoma (2.0 +/- 1.3 pmol/g wet weight, n = 4) and neuroblastoma (0.55 +/- 0.21 pmol/g wet weight, n = 3). The present study has shown that adrenomedullin is present in the human brain in high concentrations, suggesting that adrenomedullin acts as a neurotransmitter, neuromodulator or neurohormone in man.
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PMID:Adrenomedullin in human brain, adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma. 774 31

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.
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PMID:Plasma adrenomedullin concentration in patients with heart failure. 855 Jul 49

To investigate a possible pathophysiological role of human adrenomedullin (AM), we measured the plasma concentration of immunoreactive-AM (ir-AM) in 38 patients with end-stage renal disease (ESRD) on hemodialysis (HD) and 38 healthy subjects (age and sex matched). In addition, plasma ir-AM was characterized by a reverse-phase high performance liquid chromatography. The mean value (+/- SEM) of plasma AM in the patients before HD (10.1 +/- 0.67 fmol/ml) was markedly higher than that in the control group (2.9 +/- 0.13 fmol/ml, p < 0.001), but plasma AM levels were not altered by HD. There was a significant correlation between plasma AM levels and mean blood pressure (MBP) in a group of subjects including both patients before HD and healthy subjects (p < 0.01). In chromatographic study, the major peak of ir-AM in the plasma from patients on HD, as well as healthy subjects, emerged at an elution time identical to that of synthetic AM, indicating that the active form of AM was present in the circulating blood. The secretion of AM seemed to be increased in response to the conditions elicited by ESRD such as hypervolemia and/or hypertension, and reduced renal excretion of the peptide may also contribute to its high plasma level.
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PMID:Plasma concentration of human adrenomedullin in patients on hemodialysis. 871 51

Adrenomedullin has been proposed to be a circulating hormone regulating systemic and pulmonary blood pressure. A potential therapeutic role in the management of pulmonary hypertension has been suggested based on animal studies, but the pharmacokinetics and pharmacodynamics in human subjects have not been studied. We have infused adrenomedullin into volunteers at 3.2 pmol/kg.min, which more than quadrupled (52 pmol/L) normal circulating concentrations. At this dose no change in heart rate or blood pressure was noted. When infused at 13.4 pmol/kg.min to achieve a concentration over 40 times normal circulating levels (448 pmol/L), there was a significant fall in diastolic blood pressure from 69 +/- 2 to 53 +/- 2 mm Hg and a significant increase in pulse rate from 57 +/- 3 to 95 +/- 4 beats/min. Circulating PRL concentrations rose from 197 +/- 46 to 372 +/- 64 IU/L (mean +/- SEM; P < 0.01). No effect was seen on ACTH, TSH, FSH, LH, or cortisol. When the infusion was discontinued, baseline pulse and blood pressure were reestablished after 20 min. Adrenomedullin has a MCR of 27.4 +/- 3.6 mL/kg.min, with a circulating half life of 22 +/- 1.6 min and an apparent volume of distribution of 880 +/- 150 mL/kg. Column chromatography of plasma taken during infusion and decay of adrenomedullin showed no evidence of the production of additional molecular forms. These results are consistent with a peptide that is markedly tissue bound. Plasma adrenomedullin concentrations were increased in patients with renal impairment (14.1 +/- 0.9 pmol/L) compared to those in healthy volunteers (8.1 +/- 0.7 pmol/L), with a good correlation (r = 0.86) between circulating adrenomedullin and plasma creatinine. The circulating concentration of adrenomedullin necessary to affect blood pressure greatly exceeds that observed in healthy volunteers and in patients with a range of pathological conditions. Thus, adrenomedullin may be a paracrine regulator of vascular smooth muscle in humans.
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PMID:Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study. 898 40

Adrenomedullin is a potent vasodilator peptide that was originally isolated from pheochromocytoma. The production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells were studied by radioimmunoassay and northern blot hybridization. Choroid plexus carcinoma is a rare malignant tumor derived from the epithelium of the choroid plexus. Immunoreactive adrenomedullin was detected in the conditioned medium of choroid plexus carcinoma cells (40.8 +/- 7.5 fmol/10(5) cells/24 h; mean +/- SEM, n = 5). Reverse-phase HPLC of the conditioned medium showed one major peak of the immunoreactive peptide eluting in the position of synthetic human adrenomedullin and two smaller peaks eluting earlier. Addition of interleukin-1 beta (10 ng/ml) alone or in combination with three cytokines, interferon-gamma (100 U/ml), tumor necrosis factor-alpha (20 ng/ml), and interleukin-1 beta (10 ng/ml), caused significant increases in the immunoreactive adrenomedullin concentrations in the medium (approximately 175 and 293% of the control level, respectively). Northern blot analysis showed the expression of 1.6-kb adrenomedullin mRNA in the total RNA sample prepared from cultured choroid plexus carcinoma cells. Treatment with either interleukin-1 beta or the combination of three cytokines caused significant increases in levels of adrenomedullin mRNA in parallel with those in immunoreactive adrenomedullin concentrations in the conditioned medium. These findings raise a possibility that adrenomedullin is secreted from the choroid plexus and has physiological roles in the CNS via the CSF. In addition, adrenomedullin secreted from choroid plexus carcinoma may be related to the pathophysiology of the tumor.
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PMID:Production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells. 900 63

1. Adrenomedullin is a potent vasodilating peptide first isolated from phaeochromocytoma and adrenal medulla but also found in the heart, lungs and kidneys. It may also be a paracrine factor because endothelial and smooth muscle cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of nitric oxide. 2. We have developed a specific radioimmunoassay and measured the immunoreactivity of human adrenomedullin in the plasma of 58 male subjects: eight with essential hypertension, 12 with heart failure, 10 with ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to chronic obstructive pulmonary disease and 12 control subjects. 3. Plasma levels (mean +/- SEM) in patients with essential hypertension (16.3 +/- 1.9 pmol/l), congestive heart failure (17.5 +/- 2.8 pmol/l) and renal failure (17.7 +/- 2.5 pmol/l) were raised compared with control subjects (7.8 +/- 1.4 pmol/l, P < 0.05), confirming previous reports. 4. In addition, we observed that plasma levels of adrenomedullin were significantly raised in patients with ascites due to liver cirrhosis (15.5 +/- 1.9 pmol/l) and chronic obstructive pulmonary disease with hypoxia (20.0 +/- 1.5 pmol/l). 5. We concluded that the plasma level of adrenomedullin is raised in a variety of diseases.
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PMID:Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory, hepatic and renal disorders. 903 92

Adrenomedullin is a potent vasodilator peptide that was isolated from human pheochromocytoma. We developed a sensitive and specific radioimmunoassay for adrenomedullin and studied the presence of adrenomedullin in human adrenal glands and adrenal tumors, including pheochromocytoma. High concentrations of immunoreactive adrenomedullin were found in normal parts of adrenal glands (cortex and medulla) (12.6 +/- 1.0 pmol/g wet wt, N = 7, mean +/- SEM). High concentrations of immunoreactive adrenomedullin were also present in the tumor tissues of pheochromocytoma (4.5 +/- 1.5 pmol/g wet wt, N = 11). Immunoreactive adrenomedullin was detected in some adrenocortical tumors, but these concentrations were much lower than those in the normal adrenal glands and pheochromocytomas. Reverse phase high-performance liquid chromatography of the normal adrenal gland and pheochromocytoma showed a peak eluting in the position of synthetic adrenomedullin 1-52. The present study has shown the presence of high concentrations of immunoreactive adrenomedullin in the normal adrenal glands and pheochromocytomas.
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PMID:Immunoreactive adrenomedullin in human adrenal glands and adrenal tumors. 904 63

The levels of intracellular cAMP in human myometrial smooth muscle cells in serum-free medium, or medium that contained FBS (1%, vol/vol), were determined after treatment with the homologous peptides, calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), and amylin, without or with added isobutylmethylxanthine (IBMX). These cells were sensitive to CGRP, responding in a dose-dependent manner, with maximal levels of cAMP being attained with 5 nM CGRP in the presence of IBMX (1 mM). In the absence of IBMX, the level of cAMP attained in cells treated with CGRP (5 nM) (675.3 +/- 58.8 pmol.mg protein.15 min; mean +/- SEM, n = 3) was approximately 90x that in nontreated cells (7.5 +/- 0.4 pmol.mg protein.15 min). The level of cAMP in myometrial cells treated with CGRP (5 nM)+IBMX (1 mM), 1998 +/- 420 pmol.mg protein.15 min, was 29x that in cells treated with IBMX alone (69.2 +/- 10.2). The maximum level of cAMP achieved by treatment with ADM+IBMX was similar to that with CGRP+IBMX, but the dose of ADM required (1 microM) was approximately 200x that of CGRP. Amylin amide also caused an increase in cAMP but with considerably less potency; at a concentration of 500 nM, amylin amide+IBMX effected a 2.3-fold increase in cAMP relative to IBMX alone. CGRP8-37, an antagonist of CGRP via the CGRP1 receptor, inhibited the action of CGRP, ADM, and amylin in myometrial cells. Treatment with [cys(ACM)2-7]-CGRP, a CGRP2 receptor agonist, did not cause an increase in the levels of cAMP in these cells. These findings are indicative that CGRP, ADM, and amylin act via that the CGRP1 receptor in human myometrial cells. Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypetide also caused a dose-dependent increase in cAMP in myometrial cells. The findings of this study are indicative that multiple neuropeptides, acting by way of heptahelical receptors linked to the G alpha s-subunit of the G-proteins, may contribute to the maintenance of uterine quiescence during some period of human pregnancy.
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PMID:Activation of adenylyl cyclase in human myometrial smooth muscle cells by neuropeptides. 928 49


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