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.
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2022, Vol. 28 
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