Horm Metab Res 2006; 38(1): 48-52
DOI: 10.1055/s-2006-924978
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Influence of Thyroid Disorders on Kidney Angiotensinase Activity

A.  B.  Segarra1 , M.  Ramírez1 , I.  Banegas1 , F.  Hermoso1 , F.  Vargas2 , F.  Vives2 , F.  Alba3 , M.  de Gasparo4 , I.  Prieto1
  • 1Unit of Physiology, University of Jaén, Spain
  • 2Department of Physiology, University of Granada, Spain
  • 3Institute of Neuroscience “Federico Oloriz”, Granada, Spain
  • 4MGConsulting Co., Rossemaison, Switzerland
Further Information

Publication History

Received 17 May 2005

Accepted after revision 8 September 2005

Publication Date:
13 February 2006 (online)

Abstract

Thyroid disorders affect renal function, which involves changes in local renin angiotensin system (RAS). Angiotensin peptide levels in the tissue are regulated by the activity of several aminopeptidases (AP) known as angiotensinases. The nature and consequences of the thyroid-induced RAS changes are not completely understood. We investigated the relationship between thyroid status (hyper- and hypothyroidism) and several kidney AP actions involved in RAS control. We have determined fluorometrically soluble (SOL) and membrane-bound (M-B) alanylaminopeptidase (AlaAP), glutamylaminopeptidase (GluAP) and aspartylaminopeptidase (AspAP) activity using naphthylamide derivatives as substrates. Sprague-Dawley rats were divided into three groups - control, hyperthyroid, and hypothyroid. Hyperthyroidism was induced by daily subcutaneous injection of L-thyroxin (300 µg/kg/day). Hypothyroidism was induced by continuous administration of methimazole (0.03 %) in drinking water. Hypothyroid animals demonstrated a significant increase in SOL and M-B GluAP activity in renal cortex and a decrease in M-B AlaAP compared to euthyroid rats. This result may suggest higher Ang III availability. In hyperthyroid animals, M-B AlaAP and M-B AspAP activity increased significantly, which may suggest increased Ang III to Ang IV metabolism and greater formation of Ang 2 - 10, respectively. In contrast, no differences were observed between euthyroid and hypothyroid animals for SOL and M-B AP activity in renal medulla. However, hyperthyroid animals demonstrated a significant decrease in SOL and M-B GluAP activity compared to euthyroid rats, which may suggest a greater availability of Ang II in renal medulla. Alterations in angiotensin metabolism may, in part, account for some changes in renal function during thyroid disorders.

References

  • 1 Marchant C, Brown L, Sernia C. Renin-angiotensin system in thyroid dysfunction in rats.  J Cardiovasc Pharmacol. 1993;  22 449-455
  • 2 Prieto I, Hermoso F, Gasparo M, Vargas F, Alba F, Segarra A B, Banegas I, Ramirez M. Angiotensinase activities in the kidney of renovascular hypertensive rats.  Peptides. 2003;  24 755-760
  • 3 Grima M, Ingert C, Michel B, Barthelmebs M, Imbs J L. Renal tissue angiotensins during converting enzyme inhibition in the spontaneously hypertensive rat.  Clin Exp Hypertens. 1997;  19 671-685
  • 4 Chai S Y, Fernando R, Peck G, Ye S Y, Mendelsohn F A, Jenkins T A, Albiston A L. The angiotensin IV/AT4 receptor.  Cell Mol Life Sci. 2004;  61 2728-2737
  • 5 Prieto I, Segarra A B, Vargas F, Alba F, de Gasparo M, Ramirez M. Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats.  Horm Metab Res. 2003;  35 279-281
  • 6 Garcia del Rio C, Moreno M R, Osuna A, de Dios Luna J, Garcia-Estan J, Vargas F. Role of the renin-angiotensin system in the development of thyroxine-induced hypertension.  Eur J Endocrinol. 1997;  136 656-660
  • 7 Kobori H, Ichihara A, Miyashita Y, Hayashi M, Saruta T. Mechanism of hyperthyroidism-induced renal hypertrophy in rats.  J Endocrinol. 1998;  159 9-14
  • 8 García-Estañ J, Atucha N M, Quesada T, Vargas F. Involvement of the renin-angiotensin system in the reduced pressure natiuresis response of hyperthyroid rats.  Am J Physiol. 1995;  268 E897-E901
  • 9 Barlet C, Doucet A. Kinetics of triiodothyronine action on Na-K-ATPase in single segments of rabbit nephron.  Pflugers Arch. 1986;  407 27-32
  • 10 Hansen J L, Servant G, Baranski T J, Fujita T, Iiri T, Sheikh S P. Functional reconstitution of the angiotensin II type 2 receptor and Gi activation.  Circ Res. 2000;  87 753-759
  • 11 Ozono R, Wang Z Q, Moore A F, Inagami T, Siragy H M, Carey R M. Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney.  Hypertension. 1997;  30 1238-1246
  • 12 Carey R M. Update on the role of the AT2 receptor.  Curr Opin Nephrol Hypertens. 2005;  14 67-71
  • 13 Siragy H M, Inagami T, Ichiki T, Carey R M. Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor.  Proc Natl Acad Sci USA. 1999;  96 6506-6510
  • 14 Harris P J, Zhuo J L, Skinner S L. Effects of angiotensins II and III on glomerulotubular balance in rats.  Clin Exp Pharmacol Physiol. 1987;  14 489-502
  • 15 Ruiz-Opazo N. Identification of a novel dual angiotensin II/vasopressin receptor.  Nephrologie. 1998;  19 417-420
  • 16 Handa R K, Handa S E, Elgemark M K. Autoradiographic analysis and regulation of angiotensin receptor subtypes AT(4), AT(1), and AT(1 - 7) in the kidney.  Am J Physiol Renal Physiol. 2001;  281 F936-F947
  • 17 Gardiner S M, Kemp P A, March J E, Bennett T. Regional haemodynamic effects of angiotensin II (3 - 8) in conscious rats.  Br J Pharmacol. 1993;  110 159-162
  • 18 Viana A Y, Oshida Y, Han Y Q, Koshinaka K, Sato Y. Effects of imidapril, an angiotensin-converting enzyme inhibitor, on insulin sensitivity and responsiveness in streptozotocin-induced diabetic rats.  Horm Metab Res. 2004;  36 34-38
  • 19 Mustafa M R, Dharmani M, Kunheen N K, Sim M K. Effects of des-aspartate-angiotensin I on the actions of angiotensin III in the renal and mesenteric vasculature of normo- and hypertensive rats.  Regul Pept. 2004;  120 15-22
  • 20 Michel B, Grima M, Coquard C, Welsch C, Barthelmebs M, Imbs J L. Effects of triiodothyronine and dexamethasone on plasma and tissue angiotensin converting enzyme in the rat.  Fundam Clin Pharmacol. 1994;  8 366-872

Manuel Ramírez-Sánchez

Unit of Physiology · University of Jaén

23071 Jaén · Spain ·

Phone: + 34 (953) 21 23 02

Fax: + 34 (953) 212943

Email: msanchez@ujaen.es