Effect of Angiotensin 1-7 on Myocardial Calcium Pump in Salt-Sensitive Hypertensive Rats
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v2i3.455
Abstract
Objective — To investigate the effects of angiotensin 1-7 (Ang1-7) on plasma membrane ATPase isoform 1 (PMCA1) in salt-sensitive hypertensive rats. Methods — Thirty newborn male Wistar rats were selected to establish the salt-sensitive hypertensive rat model with sensory nerve injury, which were then randomly divided into 5 groups (n=5), including model group, Telmisartan group, Ramipril group, Ang1-7 group, and A-779 group. Another normal control group was established (n=5). After 4 weeks of intervention, the tail blood pressure of rats in each group was measured, and then the apical tissue of left ventricle was cut. The contents of AngⅡ and Ang1-7 in cardiomyocytes were detected by enzyme-linked immunosorbent assay. The expression of PMCA1 mRNA and protein in heart of salt-sensitive hypertensive rats were detected by RT-PCR and immunohistochemistry. Results — (1) Compared with the normal control group, the concentration of AngⅡ in the myocardium of salt-sensitive hypertensive rats increased (P < 0.05), which decreased after the intervention of Telmisartan and Ramipril (P < 0.05), and no change occurred after the intervention of Ang1-7 in concentration (P>0.05). (2) Compared with the normal control group, the concentration of myocardial Ang1-7 in salt-sensitive hypertensive rats decreased (P < 0.05), and increased after the intervention of telmisartan and ramipril (P < 0.05), and increased after the intervention of A-779 (P < 0.05). (3) The expression of PMCA1 mRNA and protein in salt-sensitive hypertensive rats was increased compared with the normal control group (P < 0.05), and the expression of Ang-(1-7), telmisartan and ramipril was decreased compared with the model group (P < 0.05). The expression of p38MAPK mRNA and p-p38MAPK protein in the myocardium of salt-sensitive hypertensive rats was increased compared with that in the normal control group (P < 0.05), and the expression of Ang-(1-7), Telmisartan and Ramipril was decreased compared with that in the model group (P < 0.05). Conclusion — Ang-(1-7) may be involved in the regulation of cardiac calcium pump, inhibiting its overcompensation and delaying the occurrence of calcium pump inhibition in the early stage of salt-sensitive hypertension. Ang-(1-7) can inhibit the activity of p38MAPK and protect the heart, and its regulation on PMCA1 may be mediated by the expression of p38MAPK pathway.
Keywords
Ang1-7, salt-sensitive hypertension, PMCA1, p38MAPK
Funding
China Regional Science Foundation Project of National Natural Science Foundation (No.: 82060085)
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[2] Latic Nejla, Erben Reinhold G. Vitamin D and Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure[J]. International journal of molecular sciences,2020,21(18).
[3] Hammad SK, Zi Min, Prehar S, et al. Ablation of the hypertension candidate gene atp2b1 results in increased blood pressure and cardiac hypertrophic remodeling[J]. Circulation, 2014, 130(Suppl 2): A13798.
[4] Hegedűs Luca, Zámbó Boglárka, Pászty Katalin, Padányi Rita, Varga Karolina, Penniston John T, Enyedi Ágnes. Molecular Diversity of Plasma Membrane Ca2+ Transporting ATPases: Their Function Under Normal and Pathological Conditions[J]. Advances in experimental medicine and biology,2020,1131{5}.
[5] Melnik M V, Afonicheva I I, Beloborodova A V. THE ROLE PLEIOTROPIC EFFECTS OF CALCIUM CHANNEL BLOCKER LERCANIDIPINE IN PERIOPERATIVE THERAPY OF ARTERIAL HYPERTENSION[J]. Anesteziologiia i reanimatologiia,2016,61(5).
[6] Cao Heng, Ke Yongsheng, Hu Zuoying. The research on the relationship between the activity of ion pump in SHR cardiomyocytes and blood pressure and left ventricular hypertrophy[J]. Chinese Journal of Pathophysiology, 2000, 16(11): 1231-1235.
[7] Hammad S, Zi M, Prehar S, et al. YIA2 PMCA1 Deletion Leads to Increased Blood Pressure and Cardiac Hypertrophy[J]. Heart (British Cardiac Society), 2014, 100(Suppl 3):A123.
[8] Laasmaa Martin, Branovets Jelena,Barsunova Karina et al. Altered calcium handling in cardiomyocytes from arginine-glycine amidinotransferase-knockout mice is rescued by creatine[J]. Am J Physiol Heart Circ Physiol, 2021, 320: H805-H825.
[9] Romero Alejandra, San Hipólito-Luengo Álvaro, Villalobos Laura A et al. The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation[J]. Aging Cell, 2019, 18: e12913.
[10] Little Robert, Zi Min, Hammad Sally K, Nguyen Loan, Njegic Alexandra, Kurusamy Sathishkumar, Prehar Sukhpal, Armesilla Angel L, Neyses Ludwig, Austin Clare, Cartwright Elizabeth J. Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries[J]. Aging cell,2017,16(5).
[11] Martínez-Revelles Sonia, García-Redondo Ana B, Avendaño María S, Varona Saray, Palao Teresa,Orriols Mar, Roque Fernanda R, Fortuño Ana, Touyz Rhian M, Martínez-González Jose, Salaices Mercedes, Rodríguez Cristina, Briones Ana M. Lysyl Oxidase Induces Vascular Oxidative Stress and Contributes to Arterial Stiffness and Abnormal Elastin Structure in Hypertension: Role of p38MAPK[J]. Antioxidants & redox signaling,2017,27(7).
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