Limits...
Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats.

Lu X, Bi YW, Chen KB - Clinics (Sao Paulo) (2015)

Bottom Line: However, its effect in hypertensive animals has not been investigated.Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score.The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and (3) recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF-1α, miR-21 and miR-210 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong University, Jinan, China.

ABSTRACT

Objectives: Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning.

Methods: Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured.

Results: Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group.

Conclusion: The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and (3) recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF-1α, miR-21 and miR-210 expression.

No MeSH data available.


Related in: MedlinePlus

Effect of RIPER on SHRs with I/R injury. (A) I/R injury led to a significant increase in the serum CK concentration. RIPER markedly decreased the serum CK concentration in olmesartan-treated SHRs, whereas the serum CK concentration is similar for vehicle-treated SHRs. *p<0.001 versus sham group. #p<0.001 versus I/R group. NS p=0.996 versus I/R group. (B) I/R injury significantly increased HIF-1α expression. Compared to the vehicle-I/R group, HIF-1α expression was significantly decreased in the vehicle-RIPER group. Compared to the olmesartan-I/R group, HIF-1α expression was significantly increased in the olmesartan-RIPER group. *p<0.001 versus sham group. NS p=0.585 versus sham group. #p<0.001 versus I/R group. (C) I/R injury markedly down-regulated miR-21 expression. miR-21 expression was comparable between the vehicle-I/R group and vehicle-RIPER group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.01 versus sham group. #p<0.001 versus I/R group. NS p=0.886 versus I/R group. (D) I/R injury significantly down-regulated miR-210 expression. miR-210 expression was significantly down-regulated in the vehicle-RIPER group compared to the vehicle-I/R group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.001 versus sham group. #p<0.01 versus I/R group. HIF-1α, hypoxia-inducible factor-1α; I/R, ischemia reperfusion; miR, microRNA; RIPER, remote ischemic perconditioning; SHR, spontaneously hypertensive rat.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496757&req=5

f4-clin_70p500: Effect of RIPER on SHRs with I/R injury. (A) I/R injury led to a significant increase in the serum CK concentration. RIPER markedly decreased the serum CK concentration in olmesartan-treated SHRs, whereas the serum CK concentration is similar for vehicle-treated SHRs. *p<0.001 versus sham group. #p<0.001 versus I/R group. NS p=0.996 versus I/R group. (B) I/R injury significantly increased HIF-1α expression. Compared to the vehicle-I/R group, HIF-1α expression was significantly decreased in the vehicle-RIPER group. Compared to the olmesartan-I/R group, HIF-1α expression was significantly increased in the olmesartan-RIPER group. *p<0.001 versus sham group. NS p=0.585 versus sham group. #p<0.001 versus I/R group. (C) I/R injury markedly down-regulated miR-21 expression. miR-21 expression was comparable between the vehicle-I/R group and vehicle-RIPER group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.01 versus sham group. #p<0.001 versus I/R group. NS p=0.886 versus I/R group. (D) I/R injury significantly down-regulated miR-210 expression. miR-210 expression was significantly down-regulated in the vehicle-RIPER group compared to the vehicle-I/R group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.001 versus sham group. #p<0.01 versus I/R group. HIF-1α, hypoxia-inducible factor-1α; I/R, ischemia reperfusion; miR, microRNA; RIPER, remote ischemic perconditioning; SHR, spontaneously hypertensive rat.

Mentions: RIPER did not have a significant influence on CK concentration in the vehicle-treated SHRs but caused a significant reduction in CK concentration in the olmesartan-treated SHRs. There was no significant difference in the CK concentration between the vehicle-I/R group (4574.2±744.2 U/l) and vehicle-RIPER group (4,503.2±806.6 U/l) in the vehicle-treated SHRs. However, the CK concentration was significantly lower in the olmesartan-RIPER group (1,710.3±252.9 U/l) than in the olmesartan-I/R group (2,919.9±441.6 U/l) in the olmesartan-treated SHRs (Figure 4A).


Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats.

Lu X, Bi YW, Chen KB - Clinics (Sao Paulo) (2015)

Effect of RIPER on SHRs with I/R injury. (A) I/R injury led to a significant increase in the serum CK concentration. RIPER markedly decreased the serum CK concentration in olmesartan-treated SHRs, whereas the serum CK concentration is similar for vehicle-treated SHRs. *p<0.001 versus sham group. #p<0.001 versus I/R group. NS p=0.996 versus I/R group. (B) I/R injury significantly increased HIF-1α expression. Compared to the vehicle-I/R group, HIF-1α expression was significantly decreased in the vehicle-RIPER group. Compared to the olmesartan-I/R group, HIF-1α expression was significantly increased in the olmesartan-RIPER group. *p<0.001 versus sham group. NS p=0.585 versus sham group. #p<0.001 versus I/R group. (C) I/R injury markedly down-regulated miR-21 expression. miR-21 expression was comparable between the vehicle-I/R group and vehicle-RIPER group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.01 versus sham group. #p<0.001 versus I/R group. NS p=0.886 versus I/R group. (D) I/R injury significantly down-regulated miR-210 expression. miR-210 expression was significantly down-regulated in the vehicle-RIPER group compared to the vehicle-I/R group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.001 versus sham group. #p<0.01 versus I/R group. HIF-1α, hypoxia-inducible factor-1α; I/R, ischemia reperfusion; miR, microRNA; RIPER, remote ischemic perconditioning; SHR, spontaneously hypertensive rat.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496757&req=5

f4-clin_70p500: Effect of RIPER on SHRs with I/R injury. (A) I/R injury led to a significant increase in the serum CK concentration. RIPER markedly decreased the serum CK concentration in olmesartan-treated SHRs, whereas the serum CK concentration is similar for vehicle-treated SHRs. *p<0.001 versus sham group. #p<0.001 versus I/R group. NS p=0.996 versus I/R group. (B) I/R injury significantly increased HIF-1α expression. Compared to the vehicle-I/R group, HIF-1α expression was significantly decreased in the vehicle-RIPER group. Compared to the olmesartan-I/R group, HIF-1α expression was significantly increased in the olmesartan-RIPER group. *p<0.001 versus sham group. NS p=0.585 versus sham group. #p<0.001 versus I/R group. (C) I/R injury markedly down-regulated miR-21 expression. miR-21 expression was comparable between the vehicle-I/R group and vehicle-RIPER group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.01 versus sham group. #p<0.001 versus I/R group. NS p=0.886 versus I/R group. (D) I/R injury significantly down-regulated miR-210 expression. miR-210 expression was significantly down-regulated in the vehicle-RIPER group compared to the vehicle-I/R group, whereas it was significantly up-regulated in the olmesartan-RIPER group compared to the olmesartan-I/R group. *p<0.001 versus sham group. #p<0.01 versus I/R group. HIF-1α, hypoxia-inducible factor-1α; I/R, ischemia reperfusion; miR, microRNA; RIPER, remote ischemic perconditioning; SHR, spontaneously hypertensive rat.
Mentions: RIPER did not have a significant influence on CK concentration in the vehicle-treated SHRs but caused a significant reduction in CK concentration in the olmesartan-treated SHRs. There was no significant difference in the CK concentration between the vehicle-I/R group (4574.2±744.2 U/l) and vehicle-RIPER group (4,503.2±806.6 U/l) in the vehicle-treated SHRs. However, the CK concentration was significantly lower in the olmesartan-RIPER group (1,710.3±252.9 U/l) than in the olmesartan-I/R group (2,919.9±441.6 U/l) in the olmesartan-treated SHRs (Figure 4A).

Bottom Line: However, its effect in hypertensive animals has not been investigated.Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score.The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and (3) recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF-1α, miR-21 and miR-210 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Qilu Hospital, Shandong University, Jinan, China.

ABSTRACT

Objectives: Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning.

Methods: Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured.

Results: Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group.

Conclusion: The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and (3) recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF-1α, miR-21 and miR-210 expression.

No MeSH data available.


Related in: MedlinePlus