Abstract：Objective: To observe the effects of angiotensin converting enzyme inhibitor Ramipril (RMP) on blood pressure in spontaneously hypertensive rats (SHR) and explore the mechanism.Methods: Fifty male SHR rats were randomly divided into SHR group, RMP+SHR group, RMP+ gamperic acid [CBX, GAP junction 43 (Cx43) blocker] +SHR group, RMP+CBX+U0126[extra cellular signal-regulated kinase 1/2 (ERK1/2) inhibitor]+SHR, n=10/ group. control group (n=10) and SHR group were given normal saline 40mL/kg i.v. The other three groups were given RMP 10mg/kg i.v., RMP 10mg/kg+CBX 13.5mg/kg i.v., RMP 10mg/kg +CBX 13.5mg/kg+U012612mg/kg i.v., respectively. After 48 h of administration, BP-6 rat noninvasive blood pressure tester, hematoxylin eosin staining and Western blot analysis were used to observe the changes of physiological indexes of rats.Results: Compared with control group, SHR group showed hypertension symptoms (all P<0.05), and the phosphorylation level of Ser368 Cx43 (p-Cx43) and phosphorylation of ERK1/2 (p-ERk1/2) were down-regulated (all P<0.05). Compared with SHR group, the blood pressure of RMP+SHR group was decreased (all P<0.05), and the expressions of p-Cx43 and p-ERK1/2 were increased (all P<0.05). Compared with RMP+SHR group, the blood pressure of RMP+CBX+SHR group was significantly increased, and the expression of P-Cx43 was decreased (all P<0.05), while the expression of p-ERK1/2 was not significantly changed (P>0.05), while the blood pressure of RMP+U0126+SHR group was significantly increased. The expression of p-Cx43 and p-ERK1/2 was decreased (P<0.05). Compared with RMP+CBX+SHR group or RMP+U0126+SHR group, the blood pressure in RMP+CBX+U0126+SHR group was increased, and the expression of p-Cx43 and p-ERK1/2 was decreased (all P<0.05). Conclusion: This study confirmed that RMP can improve the symptoms of hypertension in SHR by activating ERK1/2 -Cx43 signaling pathway.
[1] Zeitouni M,Clare RM,Chiswell K,et al.Risk factor burden and long-term prognosis of patients with premature coronary artery disease[J].Am Heart Assoc,2020,9(24):17712. [2] X Ni,L Zhang,M Peng,et al.Hydrogen sulfide attenuates hypertensive inflammation via regulating connexin expression in spontaneously hypertensive rats[J].Med Sci Monit,2018,24(1):1205-1218. [3] Gao RJ,Zhang AM,Jia QH,et al.The promoting role of Cx43 on the proliferation and migration of arterial smooth muscle cells for angiotensin II-dependent hypertension[J].Pulm Pharmacol Ther,2021,70(1):102072-102083. [4] Yu Y,Xu LS,Wu Y,et al.The antihypertensive effect of MK on spontaneously hypertensive rats through the AMPK/Akt/eNOS/NO and ERK1/2/Cx43 signaling pathways[J].Hypertens Res,2021,44(7):781-790. [5] Bruno RM,Marais L,Khettab H,et al.Deep vascular phenotyping in patients with renal multifocal fibromuscular dysplasia[J].Hypertension,2019,73(2):371-378. [6] Dai Z,Zhu MM,Peng Y,et al.Endothelial and smooth muscle cell interaction via FoxM1 signaling mediates vascular remodeling and pulmonary hypertension[J].Am Respir Crit Care Med,2018,198(6):788-802. [7] Shvetsova AA,Gaynullina DK,Tarasova OS,et al.Remodeling of arterial tone regulation in postnatal development:focus on smooth muscle cell potassium channels[J].Int Mol Sci,2021,22(11):5413-5422. [8] Dehert E,Bracke A,Lambeir AM,et al.The C-terminal cleavage of angiotensin II and III is mediated by prolyl carboxypeptidase in human umbilical vein and aortic endothelial cells[J].Biochem Pharmacol,2021,192(1):1-14. [9] Li H,Xiang Y,Fan LJ,et al.Myocardin inhibited the gap protein connexin 43 via promoted miR-206 to regulate vascular smooth muscle cell phenotypic switch[J].Gene,2017,616(2):22-30. [10] Cheng D,Tu W,Chen L,et al.MSCs enhances the protective effects of valsartan on attenuating the doxorubicin-induced myocardial injury via ANGⅡ/NOX/ROS/MAPK signaling pathway[J].Aging,2021,13(18):22556-22570. [11] Su Y,Han W,Kovacs-kasa A,et al.HDAC6 activates ERK in airway and pulmonary vascular remodeling of chronic obstructive pulmonary disease[J].Am Respir Cell Mol Biol,2021,65(6):603-614. [12] Farnsworth NL,Walter R,Piscopio RA,et al.Exendin-4 overcomes cytokine-induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets[J].Physiol,2019,597(2):431-447. [13] Lei C,Ruan Y,Cai C,et al.Role of P38 mitogen-activated protein kinase on Cx43 phosphorylation in cerebral vasospasm after subarachnoid hemorrhage[J].Int Neurosci,2019,129(5):461-469. [14] Mcnair AJ,Wilson KS,Martin PE,et al.Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia[J].Pulm Circ,2020,10(3):1-12.
2022, Vol. 28 
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