This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT1- and AT2-receptor) in the coronary endothelium (CE) and cardiomyocytes (CM) of Sprague-Dawley male rats in normal (N), normal treated with losartan (NL), streptozotocin-induced diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and diabetic co-treated with insulin and losartan (DIL). Heart perfusion was used to estimate Ang II binding affinity (τ=1/k-n) to its receptor subtypes on CE and CM. Diabetes decreased τ value on CE and increased it on CM as compared to normal. In DL group, the τ value decreased on CE but was normalised on CM. Insulin treatment alone (DI) or with losartan (DIL) restored τ to normal on both CE and CM.Western blot results for AT -receptor density showed an increase in diabetics compared to normal with no normalising effect with insulin treatment.The AT1-receptor density was normalised in the diabetic groups treated with losartan +/- insulin. Results for AT2 receptor regulation revealed a significant difference between untreated (D) and losartan-treated (DL, DIL) diabetic groups.All of these data show the interrelated pathway and cross-talk between insulin and Ang II system indicating potentially negative effects on the diabetic heart.
Clauser E.Synthesis and local and distant actions of vasoactive peptides. Annales d Endocrinologie2000;61:10-15.
2.
De Mello W., Danser AHAngiotensin II and the heart: on the intracrine renin-angiotensin system. Hypertension2000;35:1183-8.
3.
Kim S., Iwao H.Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev2000;52(1):11-34.
4.
Schwartz F., Duka A., Duka I., Cui J., Gavras H.Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression. Am J Physiol Heart Circ Physiol2004;287:H1957-H1966.
5.
Fareh J., Touyz RM, Schiffrin EL, Thibault G.Endothelin-1 and angiotensin II receptors in cells from rat hypertrophied heart. Receptor regulation and intracellular Ca2+ modulation. Circ Res1996;78:302-11.
6.
Clauser E.Molecular structure and function of angiotensin ii receptors. Nephrologie1998;19:403-10.
7.
Velloso LA , Folli F., Sun XJ, White MF, Saad MJ, Kahn CRCross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA1996;93:12490-5.
8.
Conchon S. , Miserey S., Parnot C., Monnot C., Corvol P., Clauser E.Several interesting phenotypes of the AT1 receptor produced by site-directed mutagenesis. J Am Soc Nephrol1999;10(suppl 11):S8-S14.
9.
Nouet S., Amzallag N., Li JM et al. Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem2004;279:28989-97.
10.
Anavekar NS , Solomon SDAngiotensin II receptor blockade and ventricular remodelling. JRAAS2005;6(1):43-8.
11.
Ritter O., Schuh K., Brede M., Rothlein N., Burkard N., Hein L., Neyses L.AT2 receptor activation regulates myocardial eNOS expression via the calcineurin-NF-AT pathway. FASEB J2003;17:283-5.
12.
Broxmeyer L.Diabetes mellitus, tuberculosis and the mycobacteria: two millenia of enigma. Med Hypotheses2005 ;65:433-9.
13.
Connelly K. , Kelly D., Langham R., Krum H., Gilbert REDrug therapy for the cardiac complications of diabetes. Drug Discov Today2004;1:195-200.
14.
Sander GE, Wilklow FE, Giles TDHeart failure in diabetes mellitus: causal and treatment considerations . Minerva Cardioangiol2004;52:491-503.
15.
Sylvia BVEndocrinology and the Heart. In: Crawford MH, editor. Current diagnosis & treatment in cardiology2nd ed. New York : McGraw Hill;2003 [cited 2007, February 12] available from http://www.accessmedicine.com .
16.
Al Jaroudi WA, Nuwayri-Salti N., Usta JAEffect of insulin and angiotensin II receptor subtype-1 antagonist on myocardial remodelling in rats with insulin-dependent diabetes mellitus. J Hypertens2005;23:381-92.
17.
Wang P., Almahfouz A., Giorgino F., McCowen K., Smith R.In vivo insulin signaling in the myocardium of streptozotocin-diabetic rats: opposite effects of diabetes on insulin stimulation of glycogen synthase and c-Fos. Endocrinology1999;140:1141-50.
18.
Velloso LA , Folli F., Perego L., Saad MJThe multi-faceted cross-talk between the insulin and angiotensin II signaling systems. Diabetes Metab Res Rev2006;22:98-107.
19.
Elbaz N., Bedecs K., Masson M., Sutren M., Strosberg AD, Nahmias C.Functional trans-activation of insulin receptor kinase by growth inhibitory angiotensin II AT2 receptor. Mol Endocrinol2000;14:795-804.
20.
Berk BCAngiotensin IIsignal transduction in vascular smooth muscle: pathways activated by specific tyrosine kinases. J Am Soc Nephrol1999;10(suppl 11):S62-S68.
21.
Fiordaliso F., Li B., Latini R., Sonnenblick EH, Anversa P., Leri A., Kajstura J.Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II-dependent. Lab Invest2000;80:513-27.
22.
Karam CN, Nuwayri-Salti N., Usta JA et al. Effect of systemic insulin and angiotensin II receptor subtype-1 antagonist on endothelin-1 receptor subtype(s) regulation and binding in diabetic rat heart. Endothelium2005;12:225-31.
23.
Masaki T.The discovery of endothelins. Cardiovasc Res1998;39:530-3.
24.
Teerlink JRReversal of left ventricular remodeling: role of the endothelin pathway. J Card Fail2002 ;8:S494-S499.
25.
D'Uscio LV, Shaw S., Barton M., Luscher TFLosartan but not verapamil inhibits angiotensin II - induced tissue endothelin-1 increase. Role of blood pressure and endothelial function. Hypertension1998;31:1305-10.
26.
Hopfner RL, McNeill JR, Gopalakrishnan V.Plasma endothelin-1 levels and vascular responses at different temporal stages of streptozotocin diabetes. Eur J Pharmacol1999;374:221-7.
27.
Folli F., Kahn R., Hansen H., Bouchie J., Feener P.Angiotensin II inhibits signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. J Clin Invest1997;100:2158-69.
28.
Jiang ZY, Zhou Q., Chatterjee A. et al. Endothelin-1 modulates insulin signaling through phosphatidylinositol 3kinase pathway in vascular smooth muscle cells. Diabetes1999;48:1120-30.
29.
Bikhazi AB, Khalifeh AM, Jaroudi WA et al. Endothelin-1 receptor subtypes expression and binding in a perfused rat model of myocardial infarction. Comp Biochem Physiol C Toxicol Pharmacol2003;134(1):35-43.
30.
Graiani G., Lagrasta C., Migliaccio E. et al. Genetic deletion of the p66Shc adaptor protein protects from angiotensin IIinduced myocardial damage. Hypertension2005;46:433-40.
31.
Sodhi CP, Kanwar YS, Sahai A.Hypoxia and high glucose upregulate AT1-receptor expression and potentiate ANG IIinduced proliferation in VSM cells. Am J Physiol Heart Circ Physiol2003;284:H846-H852.
32.
Wassmann S. , Nickenig G.Pathophysiological regulation of the AT1-receptor and implications for vascular disease. J Hypertens2006;24(1):S15-S21.
33.
Li C., Cao L., Zeng Q.Astragalus prevents diabetic rats from developing cardiomyopathy by downregulating angiotensin II type 2 receptors' expression. J Huazhong Univ Sci Technolog Med Sci2004;24:379-84.
34.
Sechi LA, Griffin CA, Schambelan M.The cardiac renin-angiotensin system in STZ-induced diabetes. Diabetes1994;43:1180-4.
35.
Amiri F., Garcia R.Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition. Am J Physiol Renal Physiol2000;278:F603-F612.
36.
Chen X., Cui Z., Zhang F., Chang W., Chen L., Liu L. Angiotensin II and cAMP regulate AT(1)-mRNA expression in rat cardiomyocytes by transcriptional mechanism. Eur J Pharmacol2002;448(1):1-9.
