Chronic losartan treatment up-regulates AT<inf>1</inf>R and increases the heart vulnerability to acute onset of ischemia and reperfusion injury in male rats

Minwoo A. Song, Chiranjib Dasgupta, Lubo Zhang, Meijing Wang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Inhibition of angiotensin II type 1 receptor (AT<inf>1</inf>R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT<inf>1</inf>R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT<inf>1</inf>R and PKCδ expression in the left ventricle. In contrast, AT<inf>2</inf>R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT<inf>1</inf>R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.

Original languageEnglish
Article numbere0132712
JournalPLoS One
Volume10
Issue number7
DOIs
StatePublished - Jul 13 2015

Fingerprint

Angiotensin Type 1 Receptor
Losartan
angiotensin II
ischemia
Reperfusion Injury
Rats
Up-Regulation
heart
receptors
microRNA
rats
MicroRNAs
Heart Ventricles
myocardial infarction
cardiac output
myocardial ischemia
Myocardial Ischemia
pumps
hypertension
Arterial Pressure

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chronic losartan treatment up-regulates AT<inf>1</inf>R and increases the heart vulnerability to acute onset of ischemia and reperfusion injury in male rats. / Song, Minwoo A.; Dasgupta, Chiranjib; Zhang, Lubo; Wang, Meijing.

In: PLoS One, Vol. 10, No. 7, e0132712, 13.07.2015.

Research output: Contribution to journalArticle

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abstract = "Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.",
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