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Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats.
- Source :
- Cardiovascular Research; Feb2018, Vol. 114 Issue 2, p233-246, 14p
- Publication Year :
- 2018
-
Abstract
- Aims High salt intake markedly enhances hypertension induced by angiotensin II (Ang II). We explored central and peripheral slow-pressor mechanisms which may be activated by Ang II and salt. Methods and results In protocol I, Wistar rats were infused subcutaneously with low-dose Ang II (150 ng/kg/min) and fed regular (0.4%) or high salt (2%) diet for 14 days. In protocol II, Ang II-high salt was combined with intracerebroventricular infusion of mineralocorticoid receptor (MR) blockers (eplerenone, spironolactone), epithelial sodium channel (ENaC) blocker (benzamil), angiotensin II type 1 receptor (AT<subscript>1</subscript>R) blocker (losartan) or vehicles. Ang II alone raised mean arterial pressure (MAP) ∼10 mmHg, but Ang II-high salt increased MAP ∼50 mmHg. Ang II-high salt elevated plasma corticosterone, aldosterone and endogenous ouabain but not Ang II alone. Both Ang II alone and Ang II-high salt increased mRNA and protein expression of CYP11B2 (aldosterone synthase gene) in the adrenal cortex but not of CYP11B1 (11-β-hydroxylase gene). In the aorta, Ang II-high salt increased sodium-calcium exchanger-1 (NCX1) protein. The Ang II-high salt induced increase in MAP was largely prevented by central infusion of MR blockers, benzamil or losartan. Central blockades significantly lowered plasma aldosterone and endogenous ouabain and markedly decreased Ang II-high salt induced CYP11B2 mRNA expression in the adrenal cortex and NCX1 protein in the aorta. Conclusion These results suggest that in Ang II-high salt hypertension, MR-ENaC-AT<subscript>1</subscript>R signalling in the brain increases circulating aldosterone and endogenous ouabain, and arterial NCX1. These factors can amplify blood pressure responses to centrally-induced sympatho-excitation and thereby contribute to severe hypertension. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANGIOTENSIN II
HYPERTENSION
LABORATORY rats
MESSENGER RNA
ALDOSTERONE
Subjects
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 114
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 127765252
- Full Text :
- https://doi.org/10.1093/cvr/cvx214