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Azilsartan associated with increased circulating angiotensin-(1-7) levels and reduced renovascular 20-HETE levels

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eMediNexus    15 January 2018

Activation of angiotensin (ANG) II type 1 receptors (AT1R) tends to stimulate vasoconstriction, inflammation, and renal dysfunction. A study assessed the ability of azilsartan (AZL) to modulate levels of plasma ANG-(1-7) and renal epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) in experimental models that were infused with ANG II (125 ng/min) or vehicle (VEH). AZL (3 mg/kg/day) or VEH was administered starting 1 day before ANG II or VEH infusion.

Mean 24-hour blood pressure (BP) was not different between VEH and AZL treatment groups. BP elevation with ANG II infusion (121 ± 5 mm Hg) was normalized with AZL cotreatment (86 ± 3 mm Hg). The ANG II-induced renal damage was seen to decrease and cardiac hypertrophy was prevented with AZL cotreatment. Plasma ANG-(1-7) levels (pg/ml) increased with AZL treatment (219 ± 22) and AZL + ANG II infusion (264 ± 93) compared to VEH (74.62 ± 8). AZL treatment led to an increase in the ratio of EETs to their dihydroxyeicosatrienoic acid (DHET) metabolites and reduced 20-HETE levels.

AZL treatment completely counteracted the ANG II-induced increase in BP, prevented cardiac hypertrophy, attenuated renal damage, and improved ANG-(1-7) and EET/DHET ratio; at the same time, it decreased 20-HETE levels.

The findings from the study were published in the American Journal of Hypertension.

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