Sharifi Klishadi M, Zarei F, Shekarforoush S, Safari F, Safari F. Therapeutic effects of 1,25-dihydroxyvitamin D and losartan co-administration on myocardial ischemia-reperfusion injury in rats. Physiol Pharmacol 2014; 18 (2) :156-169
URL:
http://ppj.phypha.ir/article-1-996-en.html
Abstract: (8554 Views)
Introduction: Studies support the idea that low levels of vitamin D are associated with a higher risk of heart
disease. Losartan has also been prescribed as a drug commonly used for treating hypertension. The aim of the current
study was to investigate the effects of 1,25-dihydroxyvitamin D in combination with a non-hypotensive dose of losartan
on myocardial infarct size, reperfusion-induced arrhythmia and cardiac expression of survival factors in the ischemicreperfused
rat heart.
Methods: Male rats were randomly divided into untreated ischemia-reperfused rats (IR group) and groups pretreated
with losartan (Los+IR) or vitamin D3 (VitD+IR) or both of them (Los+VitD+IR). Animals were subjected to 30
min of left coronary artery occlusion followed by 120 min of reperfusion. Infarct size measurement was performed
using tetrazolium chloride. Incidence of arrhythmia was analysed according to Lambeth convention. Gene expression
was evaluated by real time RT-PCR technique.
Results: In VitD+IR and Los+IR groups the infarct size did not differ significantly. In Los+VitD+IR group, the
infarct size was decreased by 21.4±7.3% (P<0.001 vs. IR, P<0.05 vs. VitD+IR, P<0.01 vs. Los+IR). The number of
ventricular ectopic beats was 201±32 beats in Los+VitD+IR group (P<0.001 vs. IR, P<0.01 vs. VitD+IR, P<0.05 vs
Los+IR ). The increase of thioredoxin-1 and catalase transcription levels was not significant in Los+IR and VitD+IR
groups, however, in Los+VitD+IR group the mRNA levels of these survival factors were markedly increased (P<0.001
vs IR).
Conclusion: Co-administration of a non-hypotensive dose of losartan and vitamin D3 protects the heart against
ischemia-reperfusion injury accompanied by an increase in transcription of prosurvival factors