Do increased plasma adrenomedullin levels in normotensive subjects precede hypertension?

摘要

Adrenomedullin (AM) was first discovered in 1993 in an extract of human pheochromocytoma tissue by monitoring cyclic adenosine monophosphate levels in rat platelets. A molecule of AM consists of 52 amino acids and has high hypotensive activity.Immunoreactivity for AM is widely distributed throughout the cardiovascular system. Over the past 13 years, more than 1700 peer-reviewed articles have been published regarding the biochemistry, molecular biology, physiology, pharmacology and pathophysiology of AM. Plasma and tissue AM levels are reported to be increased in patients with cardiovascular disease, such as those with hypertension, heart failure, myocardial infarction and renal failure. Of note, the magnitude of the increase in AM levels is proportional to disease severity.The findings that long-term infusion and gene transfer studies of AM in rat models of cardiovascular disease improved cardiac hypertrophy, fibrosis and dysfunction, renal fibrosis and dysfunction, and arteriosclerosis suggest that increased endogenous AM has a compensatory role in 'defending' against these conditions. More recent experimental studies in transgenic mice and heterozygote AM knockout mice also support this hypothesis.