AT1 receptors prevent salt-induced vascular dysfunction in isolated middle cerebral arteries of 2 kidney-1 clip hypertensive rats.
BACKGROUND
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.


METHODS
Male Sprague-Dawley rats were subjected to 2 kidney-1 clip (2K1C) Goldblatt hypertension for 4 weeks and compared with sham-operated controls.


RESULTS
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. AT1 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.


CONCLUSIONS
These results suggest that the sustained effects of elevated ANG II levels in 2K1C hypertension maintain endothelium-dependent vasodilatation via AT1 receptor-mediated preservation of antioxidant defense mechanisms despite significant elevations in blood pressure and salt-induced suppression of PRA.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Andreas M
AM
Beyer
Katherine
K
Fredrich
Julian H
JH
Lombard
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D012965:Sodium Chloride; D012083:Renin; D000109:Acetylcholine
angiotensin II; blood pressure; cerebral circulation; endothelial dysfunction; hypertension; oxidant stress; salt; sodium; superoxide.