Faculty Collaboration Database

AT1 receptors prevent salt-induced vascular dysfunction in isolated middle cerebral arteries of 2 kidney-1 clip hypertensive rats. Am J Hypertens 2013 Dec;26(12):1398-404

Date

08/13/2013

Pubmed ID

23934707

Pubmed Central ID

PMC3816625

DOI

10.1093/ajh/hpt129

Scopus ID

2-s2.0-84890515006 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

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.

Author List

Beyer AM, Fredrich K, Lombard JH

Author

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Animals
Diet, Sodium-Restricted
Disease Models, Animal
Endothelium, Vascular
Hypertension, Renovascular
Male
Middle Cerebral Artery
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Renin
Sodium Chloride
Vasoconstrictor Agents
Vasodilator Agents