ABC  Vol.1 No.3 , November 2011
Garlic (allium sativum) modulates the expression of angiotensin II AT2 receptor in adrenal and renal tissues of streptozotocin-induced diabetic rats
ABSTRACT
The loss of balance between the antagonistic activities of angiotensin II AT1/AT2 receptors has been impli-cated as a major mediator in the development of hypertension and progressive nephropathy in expe-rimental diabetes. The present study was designed to investigate the potential of garlic to modulate the level of expression of the AT2 receptor in the adrenal and renal tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to the AT2 receptor, as verified by Western blotting and emplo- yed in immunohistochemical assays, indicated that compared to normal rats, the highest adrenocortical AT2 receptor expression was significantly shifted from the zona glomerulosa to the zona fasciculate/ reticularis, and was significantly reduced in adrenomedul- lary chromaffin cells of control diabetic rats. In the kidney, STZ treatments were associated with a signi- ficant decrease in AT2 receptor expression throughout glomeruli and all cortical and medullary tubular segments. Compared to control diabetic rats, the labeling of the AT2 receptor in the garlic-treated diabetic group was restored among adrenocortical zona glomerulosa cells and adrenomedullary chromaffin cells and significantly reduced in the zona fasiculata, and was also restored in glomeruli and throughout renal cortical and medullary tubular segments, to le- vels comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced AT2 receptor down-regulation may be implicated in restoring the recuperative processes mediated by AT2 receptors, which interfere with the development of hypertension and nephropathy.

Cite this paper
nullMansour, M. , Al-Qattan, K. , Thomson, M. and Ali, M. (2011) Garlic (allium sativum) modulates the expression of angiotensin II AT2 receptor in adrenal and renal tissues of streptozotocin-induced diabetic rats. Advances in Biological Chemistry, 1, 93-102. doi: 10.4236/abc.2011.13011.
References
[1]   Atlas, S.A. (2007) The renin-angiotensin aldosterone system: Pathophysiological role and pharmacologic Inhi-bition. Journal of Managed Care Pharmacy, 13, S9-S20.

[2]   Siragy, H.M. (2004) AT1 and AT2 receptor in the kidney: role in health and disease. Seminars in Nephrology, 24, 93-100. doi:10.1016/j.semnephrol.2003.11.009

[3]   De Gasparo, M., Catt, K.J., Inagami, T., et al. (2000) International union of pharmacology. XXIII. The angi-otensin II receptors. Pharmacological Reviews, 52, 415-742.

[4]   Kobori, H., Nangaku, M., Navar, L.G. and Nishiyama, A. (2007) The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kid-ney disease. Pharmacological Reviews, 59, 251-287. doi:10.1124/pr.59.3.3

[5]   Kaschina, E. and Unger, T. (2003) Angiotensin AT1/AT2 receptors: Regulation, signalling and function. Blood Pressure, 12, 70-88. doi:10.1080/08037050310001057

[6]   Ozono, R., Wang, Z., Moore, A.F., Inagami, T., et al. (1997) Expression of the subtype 2 angiotensin (AT2) re-ceptor protein in rat kidney. Hypertension, 30, 1238- 1246.

[7]   Millat, L.J., Abdel-Rahman, E. and Siragy, H.M. (1999) Angiotensin II and nitric oxide: A question of balance. Regulatory Peptides, 81, 1-10. doi:10.1016/S0167-0115(99)00027-0

[8]   Carey, R.M., Howell, N.L., Jin, X.H. and Siragy, H.M. (2001) Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats. Hypertension, 38, 1272-1277.doi:10.1161/hy1201.096576

[9]   Carey, R.M. (2005) Updates on the role of the AT2 re-ceptor. Current Opinion in Nephrology and Hypertension, 14, 67-71. doi:10.1097/00041552-200501000-00011

[10]   Carey, R., Wang, Z. and Siragy, H. (2000) Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension, 35, 155-163.

[11]   Kalinyak, J.E., Sechi, L.A., Griffin, C.A., et al. (1993) The renin-angiotensin system in streptozotocin-induced diabetes mellitus in the rat. Journal of the American So-ciety of Nephrology, 4, 1337-1345.

[12]   Brown, L., Wall, D., Marchant, C. and Sernia, C. (1997) Tissue-specific changes in angiotensin II receptors in streptozotocin-diabetic rats. Journal of Endocrinology, 154, 355-362. doi:10.1677/joe.0.1540355

[13]   Wolf, G., Sharma, K., Chen, Y., et al. (1992) High glu-cose-induced proliferation in mesangial cells is reversed by autocrine TGF-β. Kidney International, 41, 369-402. 19.

[14]   Banday, A.A. and Lokhandwala, M.F. (2008) Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes increased stimulation of sodium transporters and hypertension. American Journal of Physiology― Renal Physiology, 295, F698-F706. doi:10.1152/ajprenal.90308.2008

[15]   Wolf, G., Ziyadeh, F.N. and Stahl, R.A. (1999) Angioten-sin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells. Journal of Molecular Medicine, 77, 556- 564. doi:10.1007/s001099900028

[16]   Siragy, H.M., Awad, A.A., Abadir, P.M. and Webb, R. (2003) The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-α in diabetic rats. Endocrinology, 144, 2229-2233. doi:10.1210/en.2003-0010

[17]   Wehbi, G.J., Zimpelmann, J., Carey, R.M., et al. (2001) Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors. American Journal of Physiology― Renal Physiology, 280, F254-F265.

[18]   Nakajima, M., Hutchinson, H.G., Fujinaga, M., et al. (1995) The angiotensin II type 2 (AT2) receptor antago-nizes the growth effects of the AT1 receptor: gain-of- function study using gene transfer. Proceedings of the National Academy of Sciences of the USA, 92, 10663- 10667. doi:10.1073/pnas.92.23.10663

[19]   Maric, C., Aldred, G.P., Harris, P.J. and Alcorn, D. (1998) Angiotensin II inhibits growth of cultured embryonic re-nomedullary interstitial cells through the AT2 receptor. Kidney International, 53, 92-99. doi:10.1046/j.1523-1755.1998.00749.x

[20]   Hussain, T. and Hakam, A.C. (2006) Angiotensin II AT2 receptors inhibit proximal tubular Na+, K+-ATPase activity via a NO/cGMP dependent pathway. Am. J. Physiol. Renal. Physiol., 290, F1430-F1436. doi:10.1152/ajprenal.00218.2005

[21]   Hakam, A. C., Siddiqui, A. H. and Hussain, T. (2006) Renal angiotensin II AT2 receptors promote natriuresis in streptozotocin-induced diabetic rats. American Journal of Physiology― Renal Physiology, 290, 503-508. doi:10.1152/ajprenal.00092.2005

[22]   Siragy, M.H. (2010) The angiotensin II type 2 receptor and the kidney. Journal of Renin-Angiotensin-Aldosterone System, 11, 33-36. doi:10.1177/1470320309347786v

[23]   Miller, J.A. (1999) Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus. Journal of the American Society of Nephrology, 10, 1778-1785.

[24]   Brewster, U.C. and Perazella, M.A. (2004) The renin- angiotensin-aldosterone system and the kidney: effects on kidney disease. American Journal of Medicine, 116, 263-272. doi:10.1016/j.amjmed.2003.09.034

[25]   Weir, M.R. (2007) Effects of rennin-angiotensin system inhibition on end-organ protection: Can we do better? Clinical Therapeutics, 29, 1803-1824. doi:10.1016/j.clinthera.2007.09.019

[26]   Burns, K.D. (2000) Angiotensin II and its receptors in the diabetic kidney. American Journal of Kidney Diseases, 36, 449-467.

[27]   Mapanga, R.F. and Musabayane, C.T. (2010) The renal effects of blood glucose-lowering plant-derived extracts in diabetes mellitus-an overview. Renal Failure, 32, 132- 138. doi:10.3109/08860220903367585

[28]   Kasuga, S., Ushijima, M., Morihara, N., et al. (1999) Effect of aged garlic extract (AGE) on hyperglycemia induced by immobilization stress in mice. Nippon Yaku-rigaku Zasshi, 114, 191-197. doi:10.1254/fpj.114.191

[29]   Hosseini, M., Shafiee, S.M. and Baluchnejad-mojarad, T. (2007) Garlic extract reduces serum angiotensin con-verting enzyme (ACE) activity in nondiabetic and strep-tozotocin-diabetic rats. Pathophysiology, 14, 109-112. doi:10.1016/j.pathophys.2007.07.002

[30]   Thomson, M., Al-Amin, Z.M., Al-Qattan, K.K., et al. (2007) Anti-diabetic and hypolipidaemic properties of garlic (Allium sativum) in streptozotocin-induced diabetic rats. International Journal of Diabetes and Metabolism, 15, 108-115.

[31]   Al-Qattan, K., Thomson, M. and Ali, M. (2008) Garlic (Allium sativum) and ginger (Zingiber officinale) attenuate structural nephropathy progression in streptozoto-cin-induced diabetic rats. Journal of Cancer, 44, 341.

[32]   Vazquez-Prieto, M.A., González, R.E., Renna, N.F., et al. (2010) Aqueous garlic extracts prevent oxidative stress and vascular remodeling in an experimental model of metabolic syndrome. Journal of Agricultural and Food Chemistry, 58, 6630-6635. doi:10.1021/jf1006819

[33]   Liu, C.T., Sheen, L.Y. and Lii, C.K. (2007) Does garlic have a role as an antidiabetic agent? Molecular Nutrition & Food Research, 51, 1353-1364. doi:10.1002/mnfr.200700082

[34]   Kasuga, S., Ushijima, M., Morihara, N., et al. (1999) Effect of aged garlic extract (AGE) on hyperglycemia induced by immobilization stress in mice. Nippon Yaku-rigaku Zasshi, 114, 191-197. doi:10.1254/fpj.114.191

[35]   Pedraza-Chaverrí, J., Barrera, D., Maldonado, P.D., et al. (2004) S-allylmercaptocysteine scavenges hydroxyl ra- dical and singlet oxygen in vitro and attenuates gentami-cin-induced oxidative and nitrosative stress and renal damage in vivo. B.M.C. Clinical Pharmacology, 4, 5-18.

[36]   Ahmad, M.S. and Ahmed, N. (2006) Antiglycation prop-erties of aged garlic extract: Possible role in prevention of diabetic complication. Journal of Nutrition, 136, 796S-799S.

[37]   Mansour, M.H., Al-Qattan, K., Thomson, M. and Ali, M. (2011) Garlic (Allium sativum) down-regulates the ex-pression of angiotensin II AT1 receptor in adrenal and renal tissues of streptozotocin-induced diabetic rats. Sub- mitted to publication.

[38]   Feng, Y.-H., Zhou, L., Sun, Y. and Douglas, J.G. (2005) Functional diversity of AT2 receptor orthologues in close- ly related species. Kidney International, 67, 1731-1738. doi:10.1111/j.1523-1755.2005.00270.x

[39]   Al-Qattan, K., Al-Akhawand, S. and Mansour, M.H. (2006) Immuno-histochemical localization of distinct an- giotensin II AT1 receptor isoforms in the kidneys of the Sprague-Dawley rat and the desert rodent Meriones crassus. Anatomia, Histologia, Embryologia, 35, 130- 138. doi:10.1111/j.1439-0264.2005.00649.x

[40]   Drobiova, H., Thomson, M., Al-Qattan, K., et al. (2009) Garlic increases antioxidant levels in diabetic and hyper- tensive rats determined by a modified peroxidase method. eCAM.

[41]   Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193, 265-275.

[42]   Laemmli, U.K. (1970) Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature, 227, 680-685. doi:10.1038/227680a0

[43]   Nouet, S., Amzallag, N., Li, J.M., et al. (2004) Trans- inactivation of receptor tyrosine kinases by novel angio- tensin II AT2 receptor-interacting protein, ATIP. Journal of Biological Chemistry, 279, 28989-28997. doi:10.1074/jbc.M403880200

[44]   Belloni, A.S., Andreis, P.G., Macchi, V., et al. (1998) Distribution and functional significance of angiotensin-II AT1- and AT2-receptor subtypes in the rat adrenal gland. Endocrine Research, 24, 1-15. doi:10.3109/07435809809031865

[45]   Servant, G., Dudley, D.T., Escher, E. and Guillimette, G. (1996) Analysis of the role of N-glycosylation in cell- surface expression and binding properties of angiotensin II type-2 receptor of rat pheochromocytoma cells. Bio- chemical Journal, 313, 297-304.

[46]   Mukoyama, M., Nakajima, M., Horiuchi, M., et al. (1993) Expression cloning of type 2 angiotensin II receptor re-veals a unique class of seven-transmembrane receptors. Journal of Biological Chemistry, 268, 24539-24542.

[47]   Zhuo, J., MacGregor, D.P. and Mendelsohn, F.A.O. (1996) Comparative distribution of angiotensin II receptor subtypes in mammalian adrenal glands. In: Vinson and Anderson D.C., Eds., Journal of Endocrinology Ltd, Bristol, 53-68.

[48]   Miyata, N., Park, F., Li, X.F. and Cowley Jr., A.W. (1999) Distribution of angiotensin AT1 and AT2 receptor sub- types in the rat kidney. American Journal of Physiol- ogy― Renal Physiology, 277, F437-F446.

[49]   Armando, I., Jezova, M., Bregonzio, C., et al. (2004) Angiotensin II AT1 and AT2 receptor types regulate basal and stress-induced adrenomedullary catecholamine pro- duction through transcriptional regulation of tyrosine hy-droxylase. Annals of the New York Academy of Sciences, 1018, 302-309. doi:10.1196/annals.1296.036

[50]   Chatelain, D., Montel, V., Dickes-Coopman, A., et al. (2003) Trophic and steroidogenic effects of water depri-vation on the adrenal gland of the adult female rat. Reg-ulatory Peptides, 110, 249-255. doi:10.1016/S0167-0115(02)00217-3

[51]   Lehoux, J.-G., Bird, I.M., Brier, N., et al. (1997) Influ- ence of dietary sodium restriction on angiotensin II re-ceptors in rat adrenals. Endocrinology, 138, 5238-5245. doi:10.1210/en.138.12.5238

[52]   Wang, D.H., Qiu, J. and Hu, Z. (1998) Differential regu- lation of angiotensin II receptor subtypes in the adrenal gland: Role of aldosterone. Journal of Hypertension, 32, 65-70.

[53]   Hakam, A.C. and Hussain, T. (2006) Angiotensin II type 2 receptor agonist directly inhibits proximal tubule so- dium pump activity in obese but not in lean zucker rats Journal of Hypertension, 47, 1117-1124. doi:10.1161/01.HYP.0000220112.91724.fc

 
 
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