Atrial angiotensinase activity in hypothyroid, euthyroid, and hyperthyroid rats.
Thyroid dysfunction produces marked cardiovascular responses. Hypothyroidism and hyperthyroidism cause important changes in the circulating renin-angiotensin system (RAS). Modifications in cardiac RAS have also been involved in cardiovascular alterations. Studies have revealed that thyroid hormones activate some components of cardiac RAS. Angiotensin (Ang) peptides are regulated by the activity of several aminopeptidases (AP) called angiotensinases. Previous results in our laboratory have demonstrated that thyroid dysfunction altered angiotensinase activities in hypothalamus, pituitary, and kidney. In the present study, we investigated the relationship between thyroid status and local angiotensinase activities in the atrium of hypothyroid, euthyroid, and hyperthyroid adult male rats. We have determined fluorometrically soluble and membrane-bound alanyl, glutamyl, and aspartyl aminopeptidase activities using naphthylamide derivatives as substrates. These activities have been, respectively, involved in the metabolism of Ang III to Ang IV, Ang II to Ang III, and Ang I to des-Asp Ang I. Hyperthyroidism was induced with subcutaneous injections of tetraiodothyronine (300 microg/kg/day), and the hypothyroid rats were obtained with 0.03% methimazole via the drinking water. Compared with that in euthyroid rats, a highly significant increase (by 50%) of soluble aspartyl aminopeptidase activity (P < 0.001) was observed in the atrium of hyperthyroid and hypothyroid animals. In membrane fractions, T4 treatment produced an increase in alanyl aminopeptidase (37%; P < 0.05) and aspartyl aminopeptidase activities (30%; P < 0.01). These results suggest higher formation of des-Asp Ang I in both hypothyroid and hyperthyroid rats but also suggest higher metabolism of Ang III to Ang IV in hyperthyroid animals, which is in agreement with the described alterations of cardiac RAS after thyroid dysfunction.
Segarra
Ana B
AB
Unit of Physiology, Department of Health Sciences, University of Jaén, Jaén, Spain.
Wangensteen
Rosemary
R
Ramírez
Manuel
M
Banegas
Inmaculada
I
Hermoso
Francisco
F
Vargas
Felix
F
Vives
Francisco
F
Durán
Raquel
R
Alba
Francisco
F
de Gasparo
Marc
M
Prieto
Isabel
I
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D005067:Euthyroid Sick Syndromes / Q000201:enzymology*; D006980:Hyperthyroidism / Q000201:enzymology*; D007037:Hypothyroidism / Q000201:enzymology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
C076819:angiotensinase; D010450:Endopeptidases