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PKR inhibitor imoxin prevents hypertension, endothelial dysfunction and cardiac and vascular remodelling in L-NAME-treated rats.

Abstract：

AIMS:Hypertension is one of the leading causes of cardiovascular mortality and morbidity. It is associated with severe cardiac and vascular dysfunction. Double-stranded RNA-dependent protein kinase (PKR), is a known inducer of inflammation and apoptosis. However, no research has been done to elucidate the role of the PKR in an experimental model of hypertension, and related cardiovascular complications. MAIN METHODS:L-NAME (NG-Nitro-L-arginine-methyl ester) was used to induce the hypertension. Imoxin treatment was given to Wistar rats for the four weeks along with the L-NAME, to investigate the influence on the hypertension. Changes in physiological parameter were assessed by recording non-invasive blood pressure. Expression of PKR and downstream markers for inflammation, fibrosis, and vascular damage in rat heart and aorta was determined by western blot and immunohistochemistry. Histological examination and fibrosis assessment were done by using assay kits. Vascular reactivity was determined by ex-vivo isometric tension studies on rat aortic rings. KEY FINDINGS:L-NAME-treated rats showed a significant increase in PKR expression followed by cardiac damage and vascular alterations compared to that of control animals. Results of western blot and immunohistochemistry indicate a significant increase in the inflammatory markers downstream to PKR. Endothelium-dependent vascular relaxation was significantly impaired in L-NAME administered rats. All effects of the L-NAME were attenuated by selective inhibition of PKR by imoxin. SIGNIFICANCE:Alterations in the heart and vasculature could be mediated in part by activation of the PKR pathway. Hence selective inhibition of PKR has therapeutic potential for combating hypertension and associated cardiovascular complications.

journal_name

Life Sci

journal_title

Life sciences

authors

Kalra J,Dasari D,Bhat A,Mangali S,Goyal SG,Jadhav KB,Dhar A

doi

10.1016/j.lfs.2020.118436

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

118436

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(20)31189-9

journal_volume

262

pub_type

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PKR inhibitor imoxin prevents hypertension, endothelial dysfunction and cardiac and vascular remodelling in L-NAME-treated rats.