| Prevention of salt-induced hypertension and fibrosis by AT1-receptor blockers in Dahl S rats. | |
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MedLine Citation:
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PMID: 18418273 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In Dahl S rats, high salt intake causes hypertension and cardiovascular hypertrophy and fibrosis, associated with an apparent increase in activity of tissue RAAS. In the current study, we assessed the effects of two AT1-receptor blockers (ARB) on AT1- and AT2-receptors and ACE densities and salt-induced cardiovascular changes. The hydrophilic ARB losartan (30 or 100 mg.kg.d) and the lipophilic ARB telmisartan (10 or 30 mg.kg.d) were administered once daily, and a high-salt diet was provided from 5 to 9 weeks. In Dahl S but not R rats, the high-salt diet caused marked hypertension, cardiac and kidney hypertrophy, and fibrosis. Both ARBs dose-dependently inhibited binding of Ang II to AT1-receptors and reversed the salt-induced increases in AT2-receptor densities in the CNS. Both ARBs at regular doses attenuated the salt-induced hypertension and, at high doses, prevented the increase in BP during the day but not during the night. Both ARBs similarly prevented high-salt-induced interstitial and perivascular fibrosis in the LV and RV as well as fibrosis in the aorta and renal tubules. RV hypertrophy was also prevented, but LV hypertrophy only partially, and kidney hypertrophy not at all. In Dahl S rats, AT1-receptor stimulation seems to play a critical role in salt-induced hypertension and fibrosis, but a lesser role in tissue hypertrophy. |
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Authors:
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Binhui Liang; Frans H H Leenen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 51 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-05-22 Completed Date: 2008-11-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 457-66 Citation Subset: IM |
Affiliation:
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From the Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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metabolism Angiotensin II Type 1 Receptor Blockers / administration & dosage, pharmacology, therapeutic use* Animals Aorta / drug effects, pathology Benzimidazoles / administration & dosage, pharmacology, therapeutic use Benzoates / administration & dosage, pharmacology, therapeutic use Blood Pressure / drug effects Cardiomegaly / etiology, prevention & control Dose-Response Relationship, Drug Fibrosis Heart Rate / drug effects Hypertension / etiology, prevention & control* Hypertrophy Kidney / drug effects, pathology Losartan / administration & dosage, pharmacology, therapeutic use Male Myocardium / pathology* Organ Specificity Rats Rats, Inbred Dahl Receptor, Angiotensin, Type 1 / metabolism Receptor, Angiotensin, Type 2 / metabolism Sodium, Dietary / adverse effects* |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Benzoates; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Sodium, Dietary; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 144701-48-4/telmisartan |
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