Autophagy inhibition by chloroquine prevents increase in blood pressure and preserves endothelial functions
Purpose: To determine the effects of lysosomal inhibition of autophagy by chloroquine (CHQ) on
hypertension-associated changes in the endothelial functions.
Method: Angiotensin II (Ang II)-treated human endothelial cell line EA.hy926 and renovascular
hypertensive rats were subjected to CHQ treatment (in vitro: 0.5, 1, and 2.5 μM; in vivo: 50 mg/kg/day
for three weeks). Changes in the protein expressions of LC3b II (autophagosome formation marker) and
p62 (autophagy flux marker) were assessed using immunoblotting. Cell migration assay, tubule
formation assay (in vitro), and organ bath studies (in vivo) were performed to evaluate the endothelial
functions. Hemodynamic parameters were measured as well.
Results: A higher expression of LC3b II and a reduced expression of p62 observed in the Ang II-treated
endothelial cells, as well as in the aorta of the hypertensive rats, indicated enhanced autophagy.
Treatment with CHQ resulted in reduced autophagy flux (in vitro as well as in vivo) and suppressed Ang
II-induced endothelial cell migration and angiogenesis (in vitro). The treatment with CHQ was also
observed to prevent increase in blood pressure in hypertensive rats and preserved acetylcholineinduced
relaxation in phenylephrine-contracted aorta from the hypertensive rats. In addition, chloroquine
attenuated Ang II-induced contractions in the aorta of normotensive as well as hypertensive rats.
Conclusion: These observations indicated that CHQ lowers the blood pressure and preserves the
vascular endothelial function during hypertension.
Keywords: Angiotensin II, Autophagy, Chloroquine, Endothelial function, Hypertension, Vascular
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