engleski

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries: role of oxidative stress

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague–Dawley rats. Eleven-week old, healthy male Sprague–Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilation was compared with control group. Nitric oxide (NO) synthase inhibitor Nx-nitro-L-arginine methyl ester (L-NAME) and cyclooxygenase inhibitor indomethacin (Indo) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by Indo only at D100mmHg, whereas LNAME had no effect. In losartan group, Tempol (a superoxide scavenger) restored dilatation, whereas Tempol þ L-NAME together significantly reduced FID compared with restored dilatation with Tempol alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no- flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared with control group, whereas in flow condition increased the NO and ROS production in losartan group and had no effect in the control group. In losartan group, Tempol decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of ANG II, 8-iso- PGF2a, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions ; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.

angiotensin II ; cerebral circulation ; endothelium ; flow-induced dilation ; oxidative stress

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