Source Of Adrenomedullin Research Articles

Mechanism of adrenomedullin (AM)-mediated vasodilation in rat ileum

AM, a potent vasodilator peptide is involved cardiovascular status, fluid and electrolyte homeostasis. The gut, a primary source of AM, is involved in hemodynamic response in sepsis. The purpose of this study was to elucidate the mechanisms of AM-mediated vasodilation in rat ileum. Methods: Microvascular diameters of inflow (A1) and proximal and distal premucosal arterioles (pA3 and dA3) in terminal ileum of male Sprague-Dawley rats (205-215 g) were recorded using in-vivo videomicroscopy and optical Doppler velocimetry.

Expression of the adrenomedullin gene in adipose tissue

Adrenomedullin (AM) is a potent vasodilating peptide originally isolated from human pheochromocytoma cells. This report concerns the expression and secretion of AM from adipose tissue. Northern blot analysis demonstrated marked expression of AM mRNA in mouse adipose tissue. Expression levels in adipose tissues were 2.5–3.2 times higher than in the kidney. AM mRNA level in mature adipocytes was 7.3 times higher than in the stroma–vascular fraction of adipose tissue. In mature adipocyte culture, time-dependent increase of AM peptide concentration in the culture medium was detected. AM expression was also detected in human subcutaneous adipose tissue. Adipose AM expression significantly increased in obesity mouse model, high-fat diet fed mice and ob/ob mice. These results suggest that adipose tissue, especially mature adipocytes, is major source of AM in the body, and that adipocyte-derived AM plays a pathophysiological role in obesity.

Source of plasma adrenomedullin in patients with pheochromocytoma

Controversy exists as to the origin of plasma adrenomedullin (AM). To elucidate the source of plasma AM, we measured two molecular forms of AM, an active form of mature AM (AM-m) and an intermediate inactive form of glycine-extended AM (AM-Gly), by immunoradiometric assay using specific kits in two female patients with pheochromocytoma before and 3 weeks after surgery. We also measured plasma AM-m, AM-Gly, and AM-T (AM-m + AM-Gly) levels, in addition to plasma epinephrine (E) and norepinephrine (NE) levels, in bilateral adrenal veins of one patient. Although plasma E and NE levels decreased markedly after surgery in these patients, changes in plasma AM appeared to be confined to the normal range. There were no obvious differences in plasma AM-T, AM-m, or AM-Gly levels in adrenal veins between healthy tissue and tumor sides. Furthermore, plasma AM-T, AM-m, or AM-Gly levels in adrenal veins were comparable with those in the infrarenal inferior vena cavae (IVC) or the suprarenal IVC. In contrast, plasma E and NE levels increased in the adrenal vein of the healthy side and increased further in the adrenal vein of the tumor side compared with those in the infrarenal IVC. These results suggest that the origin of plasma E and NE is the adrenal gland and that elevated plasma levels of E and NE in pheochromocytoma are due to excessive production of E and NE in the adrenal gland of the tumor side. In contrast, it is suggested that neither plasma AM levels in the adrenal vein of the healthy side nor those of the tumor side contribute to the systemic levels of plasma AM. The present results appear to be consistent with the hypothesis that the source of circulating AM is systemic vasculature.

Adrenomedullin regulates blood-brain barrier functions in vitro.

Adrenomedullin (AM) is an important vasodilator in cerebral circulation, and cerebral endothelial cells are a major source of AM. This in vitro study aimed to determine the AM-induced changes in blood-brain barrier (BBB) functions. AM administration increased, whereas AM antisense oligonucleotide treatment decreased transendothelial electrical resistance. AM incubation decreased BBB permeability for sodium fluorescein (mol. wt 376 Da) but not for Evan's blue albumin (mol. wt 67 kDa), and it also attenuated fluid-phase endocytosis. AM treatment resulted in functional activation of P-glycoprotein efflux pump in vitro. Our results indicate that AM as an autocrine mediator plays an important role in the regulation of BBB properties of the cerebral endothelial cells.

Peripheral distribution and gene expression of adrenomedullin in the rat: possible source of blood adrenomedullin

Adrenomedullin (AM) was detected in all tissues examined with the highest concentrations in adrenal gland, lung and cardiac atrium. High concentrations of pre-proadrenomedullin mRNA were also detected in the lung, cardiac atrium, adrenal gland, thoracic aorta and mesenteric artery for the first time by solution-hybridization-RNase protection assay. The molecular forms of rat AM in various tissues and plasma were also characterized by Biogel P30gel filtration chromatography. We found no significant difference in immunoreactive AM levels between the veins draining the kidney, the lung and the adrenal and the systemic arterial blood. The very low peptide/mRNA ratio and the AM/precursor ratio in the mesenteric artery and thoracic aorta suggest that blood vessels may be the main source of plasma AM.