Horm Metab Res 2003; 35(3): 164-168
DOI: 10.1055/s-2003-39071
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Effect of Losartan on Insulin Plasma Concentrations and LPL Activity in Adipose Tissue of Hypertensive Rats

T.  Saranteas 1 , E.  Lolis 2 , C.  Mourouzis 1 , A.  Potamianou 1 , C.  Tesseromatis 1 , D.  Varonos 1
  • 1 Department of Pharmacology, Medical School, University of Athens, Greece
  • 2 Department of Surgery, Aretaieion Hospital of Athens, Greece
Further Information

Publication History

Received 13 November 2001

Accepted after revision 14 October 2002

Publication Date:
07 May 2003 (online)

Abstract

The aim of this study is to determine the effect of losartan on insulin and angiotensin II (Ang II) concentrations in plasma as well as on lipoprotein lipase activity (LPL) and angiotensin II content in the adipose tissue of hypertensive rats. Fifty male rats were divided in five groups. Group A served as controls. Group B underwent renal artery stenosis. Group C were administered losartan (10 mg/kg/day) per os, while rats in group D were submitted to renal artery stenosis and were treated with losartan as above. Group E was used as sham-operated control. The animals were sacrificed at day 21. Blood samples were collected, and perirenal adipose tissue was isolated. Furthermore, adrenal's were removed and their relative weight (adrenal weight/body weight) was used as an index of sympathetic stimulation. According to our results, renovascular hypertension resulted in lower insulin concentrations and higher Ang II content in plasma. In hypertensive rats, LPL activity was decreased, while the adrenals' relative weight was elevated. On the other hand, losartan administration resulted in normalization of insulin concentrations in plasma and adrenals' relative weight, with consequent up regulation of LPL activity in adipose tissue. In conclusion, renovascular hypertension interferes in lipid metabolism by reducing LPL activity in adipose tissue, while losartan administration reverses this effect by enhancing insulin release and reducing sympathetic nervous system (SNS) stimulation.

References

  • 1 Olivecrona T, Olivecrona G. Lipoprotein and hepatic lipase in lipoprotein metabolism. In: Betteridge DJ (ed) Lipoproteins in health and disease. London; Arnold 1999: 225-239
  • 2 Eckel R H. Lipoprotein lipase: A multifactional enzyme related to common metabolic disease.  N Engl J Med. 1989;  320 1060-1068
  • 3 Beisiegel U. New aspect on role of plasma lipase in lipoprotein catabolism and atherosclerosis.  Atherosclerosis. 1996;  124 1-8
  • 4 Sadur C N, Eckel R H. Insulin stimulation of adipose tissue lipoprotein lipase.  J Clin Invext. 1982;  69 1119-1125
  • 5 Pollare T, Vessby B, Lithell H. Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity.  Aterioscler Thromb. 1991;  40 214-216
  • 6 Sechi L, Barttoli E. Molecular mechanisms of insulin resistance in arterial hypertension.  Blood Pressure. 1996;  5 47-54
  • 7 Nickeing G, Roling J, Strehlow K, Schnabel P, Bohm M. Insulin induces upregulation of vascular AT1 receptor gene expression by posttranscriptional mechanisms.  Circulation. 1998;  98 2453-2460
  • 8 Opie L H, Gersh B J. Angiotensin converting enzyme inhibitors and aldosterone antagonism. In: Opie LH (ed) Drugs for the heart. Philadelphia; WB Saunders 2001: 127-128
  • 9 Luzio S D, Dunseath G, Owens D R. Acute effects of valsartan on insulin sensitivity in obese, non hypertensive subjects with and without type 2 diabetes.  Horm Metab Res. 2002;  34 271-274
  • 10 Igarashi M, Hirata A, Yamaguchi H, Tsuchida H, Ohnuma H, Tominaga M. Candesartan inhibits carotid intimal thickening and ameliorates insulin resistance in balloon-injured diabetic rats.  Hypertension. 2001;  38 1255-1259
  • 11 Vallottori M B. The Renin-Angiotensin system.  Trends Pharmacol Sci. 1987;  8 69-74
  • 12 Kagiyama S, Varela A, Phillips I, Galli M. Antisense inhibition of brain Renin-Angiotensin System decreased blood pressure in chronic 2-kidney, 1 clip hypertensive rats.  Hypertension. 2001;  37 371-375
  • 13 Timmermans P BMWM, Wong P C, Chiu a t, Herblin W F, Benefield P, Carini D J, Lee R J, Wexler R R, Saye J AM, Smith R D. Angiotensin II receptors and angiotensin II receptor antagonists.  Pharmacological Reviews. 1993;  45 205-251
  • 14 Leung P S, Chan W P, Wong T P, Sernia C. Expression and localization of the renin- angiotensin system in the rat pancreas.  J Endocrinol. 1999;  160 13-19
  • 15 Tahmasebi M, Puddefoot J R, Inwang E R, Vinson G P. The tissue renin-angiotensin system in human pancreas.  J Endocrinol. 1999;  161 317-322
  • 16 Kelly K L, Leychock S G. Prostaglandin synthesis and metabolism in isolated pancreatic islet of the rat.  Prostaglandinds. 1981;  21 756-769
  • 17 Carlsson P O. The Renin-Angiotensin System in the endocrine pancreas.  JOP. 2001;  2 26-32
  • 18 Iwase M, Sandler S, Carlsson P O, Hellerstrom C, Jansson L. The pancreatic islets in spontaneously hypertensive rats: islet blood flow and insulin production.  Eur J Endocrinol. 2001;  144 169-178
  • 19 Carlsson P O, Berne C, Jansson L. Angiotensin II and the endocrine pancreas: effect on islet blood flow and insulin secretion in rats.  Diabetologia. 1998;  41 127-133
  • 20 Tsopanakis C, Tesseromatis C. Cold swimming stress. Effect on serum lipids, lipoproteins and LCAT activity in male and female rats.  Pharmacol Bioch Behav. 1991;  38 813-816
  • 21 Saavedra J M. Brain and pituitary angiotensin.  Endocr Rev. 1992;  13 329-380
  • 22 Matsubara H. Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases.  Circ Res. 1998;  83 1182-1191
  • 23 Moan A, Ivar K, Eide I K, Kjeldsen S E. Metabolic and adrenergic characteristics of young men with insulin resistance.  Blood Press Suppl. 1996;  1 30-37
  • 24 Deshaies Y, Geloen A, Paulin A, Marette A, Bucowiecki L J. Tissue-specific alterations in lipoprotein lipase activity in the rat after chronic infusion of isoproterenol.  Horm Metab Res. 1993;  25 13-16
  • 25 Sacks F M, Dzau V J. Adrenergic effect on plasma lipoprotein metabolism. Speculation on mechanism of action.  Am J Med. 1986;  Suppl. 2A 71-81
  • 26 Ahima R S, Filer J S. Adipose tissue as an endocrine organ.  Trends Endocrinol Metab. 2000;  11 327-332
  • 27 Engeli S, Negrel R, Sharma M. Physiology and pathophysiology of the adipose tissue Renin-Angiotensin system.  Hypertension. 2000;  35 1270-1277
  • 28 Wong P C, Chiu A T, Duncia J V. Angiotensin II receptor antagonists and receptor subtypes.  Trends Endocrinol Metab. 1992;  3 211-217
  • 29 Jansson L. The regulation of pancreatic islet blood flow.  Diabetes Metabol Rev. 1994;  10 407-416
  • 30 Allen T J, Cao Z M, Youssef S, Hulthen U L, Cooper M E. Role of local and systemic angiotensin II and bradykinin in experimental diabetic nephropathy-functional and structural studies.  Diabetes. 1997;  46 1612-1618

T. Saranteas, M.D., D.D.S., Ph.D.

Department of Pharmacology · Medical School · University of Athens ·

M. Asias 75 · Goudi 11527 · Athens · Greece ·

Phone: + 301-7776532

Fax: + 301-7462554 ·

Email: mourior1@otenet.gr