Adrenomedullin Gene Expression and Peptide Levels in the Heart and Blood Vessels of Streptozotocin-diabetic Rats

Abstract

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.

Adrenomedullin and the calcitonin receptor-like receptor system mRNA expressions in the rat heart and sensory ganglia in experimentally-induced long-term diabetes

“…STZ treatment of rats led to an increased AM mRNA expression in heart ventricles but not in the atria 2 and 4 weeks after the application. Interestingly, this increase was not paralleled by an increase in AM peptide content (Tang et al 2007). AM has been reported to act in an autocrine/paracrine fashion to prevent cardiovascular damage (Shimekake et al 1995).…”

“…In many cardiovascular disorders, expression of AM was increased, e.g. in hypertension (Pan et al 2006), congestive heart failure (Jougasaki et al 1996;Oie et al 2000), cardiac ischemia (Oie et al 2000) and short time diabetes (He et al 2007;Tang et al 2007). Most of these pathologies are associated with increased plasma levels of AM that are related to disease severity (Brain and Grant 2004).…”

“…Specifically in diabetes, AM improves cardiac function and has been considered as a promising new therapeutic approach (Dobrzynski et al 2002;Adeghate 2004). Except for a notion of fluctuating values of preproAM mRNA in the rat heart at 2 and 4 weeks (Tang et al 2007) and unaltered expression in the left ventricle at 7 weeks after streptozotocin (STZ) administration (Ruzicska et al 2004), it is currently unclear to which extent the endogenous cardiac AM signaling system is affected in the course of the disease, particularly in long-term diabetes.…”

“…On the background of these proposed links of AM to diabetic cardiomyopathy (Dobrzynski et al 2002;Adeghate 2004;Tang et al 2007) and to glucose-dependent neuronal damage (Tixier et al 2008), we set out to determine gene expression of AM and the components of its receptor system in the various compartments of the rat heart (right and left atria and ventricles) in the course of STZ-induced long-term (8 and 26 weeks) diabetes. Since sensory neurons are also both target and source of AM/CGRP peptides (Cottrell et al 2005;Hong et al 2009) and are affected in long-term diabetes (Toth et al 2007), we also investigated the expression of this signaling system in sensory ganglia providing the extrinsic innervation to the heart 26 weeks after STZ application.…”