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Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats.
- Source :
-
Cardiovascular research [Cardiovasc Res] 2018 Feb 01; Vol. 114 (2), pp. 233-246. - 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.<br />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 (AT1R) 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.<br />Conclusion: These results suggest that in Ang II-high salt hypertension, MR-ENaC-AT1R 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.<br /> (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)
- Subjects :
- Aldosterone blood
Animals
Brain metabolism
Cardenolides metabolism
Cytochrome P-450 CYP11B2 metabolism
Disease Models, Animal
Epithelial Sodium Channels metabolism
Hypertension chemically induced
Hypertension metabolism
Male
Rats, Wistar
Receptor, Angiotensin, Type 1 metabolism
Receptors, Mineralocorticoid metabolism
Saponins metabolism
Sodium-Calcium Exchanger metabolism
Sympathetic Nervous System metabolism
Time Factors
Angiotensin II
Arterial Pressure
Brain physiopathology
Cardiovascular System innervation
Hypertension physiopathology
Renin-Angiotensin System
Sodium Chloride, Dietary
Sympathetic Nervous System physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1755-3245
- Volume :
- 114
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 29126194
- Full Text :
- https://doi.org/10.1093/cvr/cvx214