AT(1) Receptors Prevent Salt-Induced Vascular Dysfunction in Isolated Middle Cerebral Arteries of 2 Kidney-1 Clip Hypertensive Rats

作者：Beyer Andreas M; Fredrich Katherine; Lombard Julian H^*

来源：American Journal of Hypertension, 2013, 26(12): 1398-1404.

DOI：10.1093/ajh/hpt129

• angiotensin II
• blood pressure
• cerebral circulation
• endothelial dysfunction
• hypertension
• oxidant stress
• salt
• sodium
• superoxide

BACKGROUND %26lt;br%26gt;Elevated blood pressure, elevated angiotensin II (ANG II), and ANG II suppression with high salt (HS) diet all contribute to vascular dysfunction. This study investigated the interplay of HS diet and vascular function in a high renin model of hypertension. %26lt;br%26gt;METHODS %26lt;br%26gt;Male Sprague-Dawley rats were subjected to 2 kidney-1 clip (2K1C) Goldblatt hypertension for 4 weeks and compared with sham-operated controls. %26lt;br%26gt;RESULTS %26lt;br%26gt;Middle cerebral arteries (MCA) of 2K1C rats and sham-operated controls fed normal salt (NS; 0.4% NaCl) diet dilated in response to acetylcholine (ACh) and reduced partial pressure of oxygen (PO2). Switching to HS (4% NaCl) diet for 3 days to reduce plasma renin activity (PRA) eliminated vasodilation to ACh and reduced PO2 in sham-operated controls, with no effect on vasodilation in 2K1C rats. AT(1) receptor blockade (losartan, 20 mg/kg/day; 1 week) eliminated vasodilator responses to ACh and reduced PO2 in 2K1C rats fed NS or HS diet. ANG II infusion (5 ng/kg/min, intravenous) for 3 days to prevent salt-induced reductions in plasma ANG II restored vascular relaxation in MCA of sham-operated controls fed HS diet. Copper/zinc superoxide dismutase expression and total superoxide dismutase activity were significantly higher in arteries of 2K1C rats fed HS diet vs. sham-operated controls. %26lt;br%26gt;CONCLUSIONS %26lt;br%26gt;These results suggest that the sustained effects of elevated ANG II levels in 2K1C hypertension maintain endothelium-dependent vasodilatation via AT(1) receptor-mediated preservation of antioxidant defense mechanisms despite significant elevations in blood pressure and salt-induced suppression of PRA.

• 出版日期2013-12