RESUMEN
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.
Asunto(s)
Adrenomedulina/metabolismo , Vasos Sanguíneos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Miocardio/metabolismo , Adrenomedulina/sangre , Adrenomedulina/genética , Adrenomedulina/orina , Animales , Aorta Torácica/metabolismo , Vasos Sanguíneos/química , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/orina , Ventrículos Cardíacos/metabolismo , Masculino , Arterias Mesentéricas/metabolismo , Miocardio/química , Péptidos/análisis , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
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.
Asunto(s)
Médula Suprarrenal/metabolismo , Expresión Génica , Péptidos/genética , Estrés Fisiológico/metabolismo , Médula Suprarrenal/efectos de los fármacos , Adrenalectomía , Hormona Adrenocorticotrópica/sangre , Adrenomedulina , Animales , Corticosterona/sangre , Éter , Bloqueadores Ganglionares/farmacología , Expresión Génica/efectos de los fármacos , Hexametonio/farmacología , Masculino , Precursores de Proteínas/biosíntesis , Precursores de Proteínas/genética , Ratas , Ratas Sprague-Dawley , Estrés Fisiológico/inducido químicamente , Estrés Fisiológico/genéticaRESUMEN
Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis and in inflammation. We examined its expression in a rat model of endotoxaemia. Male Sprague-Dawley rats received intraperitoneal injection of 5 or 10 mg/kg lipopolysaccharide (LPS), or saline as control. Rats were killed at 1, 3, 6, 12 and 24 h after injection. LPS at 5 mg/kg, but not saline, increased plasma AM significantly at 3 h. At 10 mg/kg, plasma AM was raised at 3, 6 and 12 h. Immunoreactive AM concentration in lung increased after 5 or 10 mg/kg LPS, but not saline. PreproAM mRNA level in lung was significantly increased at 3 and 6 h. In conclusion, endotoxin stimulates the expression of AM in the lungs and increases its circulatory concentration. AM may be involved in the systemic response to sepsis.