Adrenomedullin gene expression and peptide levels in the heart and blood vessels of streptozotocin-diabetic rats

The aim of the present study was to assess the changes in gene expression and peptide adrenomedullin (AM) levels in cardiovascular and other tissues in the streptozotocin-diabetic rats. For this purpose, diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/Kg body weight). Half of the diabetic rats were subcutaneously injected with insulin in the afternoon (4 units/day) one week after STZ injection until the day before killing. Control rats received only saline injection. AM mRNA was determined in cardiovascular and other tissues of streptozotocin-diabetic rats using solution-hybridization- RNase protection assay. Circulating AM and peptide AM in cardiovascular and other tissues were estimated using a specific radioimmunoassay. There were increases in preproAM mRNA levels in the left and right ventricles and in the thoracic aorta in both the 2-week and 4-week diabetic rats, but not in the two atria, the mesenteric artery and the lung. In the 2-week diabetic rats, there were decreases in AM contents in the two atria and the lung but an increase in the thoracic aorta. In the 4-week diabetic rats, there were bigger decreases in the atria and also a decrease in the left ventricle. The plasma AM levels were not changed but there was an increase in the excretion of AM in the urine. Our results suggest a possible increase in AM release in the heart and the thoracic aorta in the 2-week and 4-week diabetic rats. © Georg Thieme Verlag KG Stuttgart.link_to_subscribed_fulltex

Ether stress increases adrenomedullin gene expression and levels in the rat adrenal

To study the contribution of adrenomedullin in the adrenal medulla in the stress response, we measured plasma and adrenal levels of adrenomedullin in sham-operated (intact) rats and in rats without adrenal medulla, with or without exposure to ether vapor for 15 min. Adrenomedullin levels decreased drastically after demedullation. Effect stress resulted in increased adrenomedullin levels in both adrenal and plasma in sham-operated rats, but not in demedullated rats. The responses of plasma adrenocorticotropin to stress were similar, but the elevations in plasma corticosterone levels were significantly less in demedullated rats. In the sham-operated rat, preproadrenomedullin mRNA levels were increased after stress, and this effect was not blocked by pretreatment with hexamethonium. We conclude that stress increases adrenomedullin synthesis and secretion from the adrenal medulla through a hexamethonium-insensitive mechanism, and that adrenomedullin release from the adrenal medulla may play a role in cortical steroidogenesis. © Georg Thieme Verlag KG Stuttgart.link_to_subscribed_fulltex

The hemodynamic effects of in-tandem carotid artery stenosis: implications for carotid endarterectomy.

OBJECTIVES: It remains controversial whether patients with severe disease of the internal carotid artery and a coexisting stenotic lesion downstream would benefit from a carotid endarterectomy (CEA) of the proximal lesion. The aim of this study was to simulate the hemodynamic and wall shear effects of in-tandem internal carotid artery stenosis using a computational fluid dynamic (CFD) idealized model to give insight into the possible consequences of CEA on these lesions. METHODS: A CFD model of steady viscous flow in a rigid tube with two asymmetric stenoses was introduced to simulate blood flow in arteries with multiple constrictions. The effect of varying the distance between the two stenoses, and the severity of the upstream stenosis on the pressure and wall shear stress (WSS) distributions on the second plaque, was investigated. The influence of the relative positions of the two stenoses was also assessed. RESULTS: The distance between the plaques was found to have minimal influence on the overall hemodynamic effect except for the presence of a zone of low WSS (range -20 to 30 dyne/cm2) adjacent to both lesions when the two stenoses were sufficiently close (<4 times the arterial diameter). The upstream stenosis was protective if it was larger than the downstream stenosis. The relative positions of the stenoses were found to influence the WSS but not the pressure distribution. CONCLUSIONS: The geometry and positions of the lesions need to be considered when considering the hemodynamic effects of an in-tandem stenosis. Low WSS is thought to cause endothelial dysfunction and initiate atheroma formation. The fact that there was a flow recirculation zone with low WSS in between the two stenoses may demonstrate how two closely positioned plaques may merge into one larger lesion. Decision making for CEA may need to take into account the hemodynamic situation when an in-tandem stenosis is found. CFD may aid in the risk stratification of patients with this problem

Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Relationships to β-amyloid deposition and neurotransmitter abnormalities

Transgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Aβ42 production and provide a model of Alzheimer-type amyloidosis. Here, we examine cognition in 6- and 18-month old transgenic mice expressing APPswe and PS1dE9, alone and in combination. Spatial reference memory was assessed in a standard Morris Water Maze task followed by assessment of episodic-like memory in Repeated Reversal and Radial Water maze tasks. We then used factor analysis to relate changes in performance in these tasks with cholinergic markers, somatostatin levels, and amyloid burden. At 6 months of age, APPswe/PS1dE9 double-transgenic mice showed visible plaque deposition; however, all genotypes, including double-transgenic mice, were indistinguishable from nontransgenic animals in all cognitive measures. In the 18-month-old cohorts, amyloid burdens were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). APPswe/PS1dE9 mice performed all cognitive tasks less well than mice from all other genotypes. Factor and correlation analyses defined the strongest correlation as between deficits in episodic-like memory tasks and total Aβ loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Aβ associated with amyloid deposition can disrupt cognitive circuits when the cholinergic and somatostatinergic systems remain relatively intact; and that episodic-like memory seems to be more sensitive to the toxic effects of Aβ. © 2004 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex