Relations of angiotensin-(1-7) with hemodynamic and cardiac structural and functional parameters in patients with hypertension and type 2 diabetes
Abstract
Background. The angiotensin-(1-7) is a new component of the renin-angiotensin system, the product of the degradation of angiotensin II and its functional antagonist, but its role in hypertension with type 2 diabetes (T2D) is not clear. The aim of the study was to investigate the levels of angiotensin-(1-7) in patients with hypertension and T2D and determine its relations to hemodynamic and cardiac structural and functional parameters.
Material and methods. We examined 70 patients with hypertension and T2D. Investigation protocol included physical examination, standard transthoracic echocardiography and determination of the angiotensin-(1-7) blood levels by ELISA. Control group consisted of 16 healthy volunteers.
Results. The angiotensin-(1-7) levels in observed patients were significantly lower than in volunteers [105.51 (89.13;121.17) ng/L vs. 132.75 (125.06; 142.87) ng/L, p < 0.001]. The levels of the angiotensin-(1-7) significantly negatively correlated with duration of hypertension (r = –0.29, p < 0.05), systolic blood pressure (BP) (r = –0.38, p < 0.05), diastolic BP (r = –0.36, p < 0.01), average BP (r = –0.32, p < 0.01), left ventricular (LV) internal dimension at end-diastole (r = –0.37, p < 0.01), LV mass (r = –0.40, p < 0.001), LV mass index (r = –0.41, p < 0.001). In patients with LV hypertrophy, angiotensin-(1-7) levels were significantly lower than in patients without LV hypertrophy [101.9 (88.2; 117.7) ng/L vs. 129.3 (117.5; 136.8) ng/L, p < 0.01] and in patients with diastolic LV dysfunction — lower than in the patients with normal diastolic function [101.1 (87.9; 116.6) ng/L vs. 121.1 (105.5; 128.9) ng/L, p < 0.01].
Conclusions. The angiotensin-(1-7) can be considered as an important pathogenetic factor in the development of hypertension with T2D, a BP regulator and a cardioprotective agent that prevents the development of remodeling and diastolic dysfunction of the LV.
Keywords: angiotensin-(1-7)hypertensiontype 2 diabetesleft ventricular remodelingdiastolic dysfunction
References
- Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018; 34(5): 575–584.
- Lau WB, Ohashi K, Wang Y, et al. Role of Adipokines in Cardiovascular Disease. Circ J. 2017; 81(7): 920–928.
- Brzeska A, Sołtysiak M, Ziemak J, et al. Plasma adiponectin in hypertensive patients with and without metabolic syndrome. Arterial Hypertension. 2018; 22(1): 29–36.
- Koval S, Iushko K, Starchenko T. Relations of Apelin with Cardiac Remodeling in Patients with Hypertension and Type 2 Diabetes. Folia Med (Plovdiv). 2018; 60(1): 117–123.
- Wu CH, Mohammadmoradi S, Chen JZ, et al. Renin-Angiotensin System and Cardiovascular Functions. Arterioscler Thromb Vasc Biol. 2018; 38(7): e108–e116.
- Patel VB, Zhong JC, Grant MB, et al. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure. Circ Res. 2016; 118(8): 1313–1326.
- Karnik SS, Singh KD, Tirupula K, et al. Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22. Br J Pharmacol. 2017; 174(9): 737–753.
- Santos RA. Angiotensin-(1-7). Hypertension. 2014; 63(6): 1138–1147.
- McKinney CA, Fattah C, Loughrey CM, et al. Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodelling. Clin Sci (Lond). 2014; 126(12): 815–827.
- Machado-Silva A, Passos-Silva D, Santos RA, et al. Therapeutic uses for Angiotensin-(1-7). Expert Opin Ther Pat. 2016; 26(6): 669–678.
- Mancia G, Fagard R, Narkiewicz K, et al. Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31(7): 1281–1357.
- Rydén L, Grant PJ, Anker SD, et al. Authors/Task Force Members, ESC Committee for Practice Guidelines (CPG), Document Reviewers. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013; 34(39): 3035–3087.
- Lang RM, Bierig M, Devereux RB, et al. American Society of Echocardiography's Nomenclature and Standards Committee, Task Force on Chamber Quantification, American College of Cardiology Echocardiography Committee, American Heart Association, European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr. 2006; 7(2): 79–108.
- Rickham PP. Human experimentation. Code of Ethics of the World Medical Association. Declaration of Helsinki. Br Med J. 1964; 2(5402): 177.
- Jalil JE, Palomera C, Ocaranza MP, et al. Levels of plasma angiotensin-(1-7) in patients with hypertension who have the angiotensin-I-converting enzyme deletion/deletion genotype. Am J Cardiol. 2003; 92(6): 749–751.
- Sasaki S, Higashi Y, Nakagawa K, et al. Effects of angiotensin-(1-7) on forearm circulation in normotensive subjects and patients with essential hypertension. Hypertension. 2001; 38(1): 90–94.
- Shi Y, Lo CS, Padda R, et al. Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice. Clin Sci (Lond). 2015; 128(10): 649–663.
- Benter IF, Yousif MHM, Anim JT, et al. Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol. 2006; 290(2): H684–H691.
- Raffai G, Lombard JH. Angiotensin-(1-7) Selectively Induces Relaxation and Modulates Endothelium-Dependent Dilation in Mesenteric Arteries of Salt-Fed Rats. J Vasc Res. 2016; 53(1-2): 105–118.
- Yousif MHM, Benter IF, Diz DI, et al. Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity. Peptides. 2017; 90: 10–16.
- Li He, Liu X, Ren Z, et al. Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats. Cell Physiol Biochem. 2016; 40(5): 1186–1197.
- Santiago NM, Guimarães PS, Sirvente RA, et al. Lifetime overproduction of circulating Angiotensin-(1-7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling. Hypertension. 2010; 55(4): 889–896.
- López-de la Vega C, Rosas-Peralta M, Lomelí-Estrada C, et al. [Urinary levels of angiotensin-(1-7) and angiotensin II in patients with severe aortic stenosis]. Arch Cardiol Mex. 2011; 81(4): 292–297.
- Guo L, Yin A, Zhang Qi, et al. Angiotensin-(1-7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism. Am J Physiol Heart Circ Physiol. 2017; 312(5): H980–H991.
- Wang Lj, He Jg, Ma H, et al. Chronic administration of angiotensin-(1-7) attenuates pressure-overload left ventricular hypertrophy and fibrosis in rats. Di Yi Jun Yi Da Xue Xue Bao. 2005; 25(5): 481–487.
- Giani JF, Muñoz MC, Mayer MA, et al. Angiotensin-(1-7) improves cardiac remodeling and inhibits growth-promoting pathways in the heart of fructose-fed rats. Am J Physiol Heart Circ Physiol. 2010; 298(3): H1003–H1013.
- Lei Y, Xu Q, Zeng Bo, et al. Angiotensin-(1-7) protects cardiomyocytes against high glucose-induced injuries through inhibiting reactive oxygen species-activated leptin-p38 mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2 pathways, but not the leptin-c-Jun N-terminal kinase pathway in vitro. J Diabetes Investig. 2017; 8(4): 434–445.
- Hao PP, Chen YG, Liu YP, et al. Association of plasma angiotensin-(1-7) level and left ventricular function in patients with type 2 diabetes mellitus. PLoS One. 2013; 8(5): e62788.
- Lin Li, Liu X, Xu J, et al. Mas receptor mediates cardioprotection of angiotensin-(1-7) against Angiotensin II-induced cardiomyocyte autophagy and cardiac remodelling through inhibition of oxidative stress. J Cell Mol Med. 2016; 20(1): 48–57.