Tissue-specific modulation of angiotensin-converting enzyme (ACE) in hyperthyroidism.
We have previously demonstrated the interaction between the RAS and thyroid hormones (TH). The present study was designed to determine the role of TH in the local regulation of ACE activity and expression in different tissues. Adult male Wistar rats were randomized into three groups: T4-25 and T4-100 (0.025 and 0.100mg/kg of body weight/day of l-thyroxine for 14 days, respectively) and control. Hemodynamic parameters as well as cardiac and renal hypertrophy were evaluated. ACE activity and mRNA levels were determined by Fluorimetric and Northern blot assays, respectively. Both doses increased SBP and HR, as well as inducing cardiac and renal hypertrophy. Pulmonary and serum ACE levels were comparable among the groups. Both doses promoted increased renal ACE activity and expression but surprisingly ACE was diminished in the heart in both hyperthyroid groups. This change was mediated by a tissue-specific transcription mechanism.
Carneiro-Ramos
M S
MS
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, Brazil.
Silva
V B
VB
Santos
R A S
RA
Barreto-Chaves
M L M
ML
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000235:genetics; D013974:Thyroxine / Q000494:pharmacology
D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D013974:Thyroxine