Effects of adrenomedullin on cell proliferation in rat adventitia induced by aldosterone
| Autor: | Chun-Shui Pan, Jing-Hui Yang, Chaoshu Tang, Yong-Zheng Pang, Yong-Feng Qi, Wei Jiang |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Physiology medicine.drug_class Radioimmunoassay Gene Expression Rats Sprague-Dawley Adrenomedullin Paracrine signalling chemistry.chemical_compound Organ Culture Techniques Mineralocorticoid receptor Adventitia Internal medicine Internal Medicine Animals Medicine Drug Interactions RNA Messenger Protein Precursors Extracellular Signal-Regulated MAP Kinases Autocrine signalling Aldosterone Aorta Cell Proliferation business.industry Rats Enzyme Activation medicine.anatomical_structure Endocrinology chemistry Connective Tissue Mineralocorticoid Peptides Cardiology and Cardiovascular Medicine business Thymine |
| Zdroj: | Journal of Hypertension. 22:1953-1961 |
| ISSN: | 0263-6352 |
| DOI: | 10.1097/00004872-200410000-00018 |
| Popis: | Objective Aldosterone is involved in cardiovascular diseases such as hypertension and heart failure by inducing sodium retention and vascular remodeling, which is characterized by fibroblast proliferation and migration in adventitia. It is well known that aldosterone stimulates vascular smooth muscle cells and fibroblasts to produce and secrete adrenomedullin (ADM), a multiple functional peptide with an important cytoprotective effect against cardiovascular damage. We examined the effect of aldosterone on ADM production and secretion and its mRNA expression in rat aortic adventitia to study the paracrine/autocrine interaction between endogenous ADM and aldosterone. Methods ADM produced and secreted from adventitia stimulated by aldosterone in the absence or presence of spironolactone, RU486 or spironolactone together with RU486 were detected by radioimmunoassay, proliferation in adventitia cells was evaluated by the level of [ 3 H]-thymine incorporation, and preproADM gene expression was measured by semi-quantitative reverse transcriptase polymerase chain reaction. Results Adventitial ADM secretion and mRNA expression stimulated by aldosterone were concentration-dependent as was the inhibitive effect of ADM on aldosterone-induced proliferation. The induction of aldosterone in ADM secretion was mediated by mineralocorticoid receptor. Antagonists of specific receptors of calcitonin gene-related peptide (CGRP) receptor type 1 and ADM both potentiated the proliferation effect-induced by aldosterone; and thiorphan, an inhibitor of the enzyme for ADM degradation, inhibited the adventitial [ 3 H]-thymine incorporation induced by aldosterone. ADM inhibited the activity of extracellular signal related kinase (ERK) stimulated by aldosterone. Conclusion Aldosterone stimulates adventitia to produce and secrete ADM, which in turn, antagonizes the aldosterone-induced proliferation in adventitia. |
| Databáze: | OpenAIRE |
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