Regulation of the gene-encoding angiotensin II receptor in vascular tissue.
Specific angiotensin (Ang)-dependent mechanisms significantly contribute to vascular development and function, and to the pathophysiology of hypertension. The effects of Ang II are mediated by binding to specific receptors. The focus of most studies has been changes in vascular function and structure in response to Ang II. Relatively little is known regarding the molecular basis of changes in the vascular Ang II receptor. We have recently found that, without altering blood pressure, Ang II infusion at a dose of 25 ng.kg.min-1 decreases expression of the gene-encoding Ang II type 1 (AT1) receptor in both the aorta and resistant arteries. This suggests that exogenous Ang II negatively regulates AT1 mRNA expression in these tissues. Furthermore, hypertension induced by reduced renal mass plus high salt intake upregulates AT1 mRNA expression in the hypertrophied aorta and heart. In this model, the reduction of Ang II formation by captopril without decreasing blood pressure prevents the increase in AT1 mRNA in the aorta but not in the heart. This suggests that the regulation of AT1 gene expression in the heart may be pressure-dependent while there is an Ang II-dependent mechanism operant in the aorta. The precise tissue-specific control mechanisms for AT1 gene expression remain to be defined.
Wang
D H
DH
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1065, USA.
Du
Y
Y
Yao
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure; D015536:Down-Regulation / Q000187:drug effects*; D005246:Feedback; D006801:Humans; D006984:Hypertrophy; D008253:Macaca mulatta; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics*; D012982:Sodium, Dietary / Q000494:pharmacology
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II