Chronic At1 receptor blockade alters the mechanisms mediating hypoxic dilation in middle cerebral arteries

被引:13
|
作者
Phillips, SA [1 ]
Lombard, JH [1 ]
机构
[1] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
关键词
angiotensin II; angiotensin II receptors; cerebral circulation; endothelium;
D O I
10.1097/01.fjc.0000184118.76188.8c
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The purpose of this study was to determine whether chronic blockade of the angiotensin II (ANG II) AT(1) receptor under normal physiological conditions impairs vascular relaxation mechanisms in isolated middle cerebral arteries (MCA). Male Sprague-Dawley rats on a standard diet were given losartan (1 mg/mL) in the drinking water or normal water ad libitum for 7 days. Vessel diameters were measured by television microscopy before and during exposure to various vasodilator agonists and reductions in PO2 from 140 mm Hg to 35-45 mm Hg. Dilations to acetylcholine (1 mu M), the stable prostacyclin analogue iloprost (10 pg/mL), and the G(s) protein activator cholera toxin (1 ng/mL) were completely eliminated in vessels from losartan-treated animals. However, middle cerebral arteries from control and losartan-treated rats still demonstrated significant dilations in response to reduced PO2. Hypoxic dilation of middle cerebral arteries from control rats was eliminated by indomethacin (1 mu M) and unaffected by the NOS inhibitor L-NAME (100 mu M) whereas dilation in response to reduced PO2 in middle cerebral arteries from losartan-treated rats was eliminated by L-NAME and unaffected by indomethacin. Middle cerebral arteries from control and losartan-treated animals exhibited similar dilations in response to the NO-donor sodium nitroprusside (1 mu M). These data suggest that AT(1) receptor activation is important in maintaining normal vascular relaxation mechanisms in cerebral resistance arteries during normal physiological conditions, and that AT(1) receptor blockade causes a shift in the mechanisms of hypoxic dilation of middle cerebral arteries from cyclooxygenase metabolites to NO.
引用
收藏
页码:706 / 712
页数:7
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