Abstract | OBJECTIVES: METHODS:
Embolic stroke was induced by injection of calibrated microspheres (50 microm) in the right internal carotid in Sprague-Dawley rats. RESULTS: Inhibition of production of endogenous angiotensins by pretreatment for 24 h with lisinopril significantly increased mortality and infarct volume, whereas candesartan for 24 h reduced blood pressure to the same extent but had no deleterious effect. A more sustained pretreatment with candesartan for 5 days significantly decreased mortality, neurological deficit and infarct size. The AT2 receptor antagonist PD123319 and the AT4 receptor antagonist divalinal abolished the protective effect of 5 days' AT1 blockade. Combined blockade of AT2 and AT4 in candesartan pretreated rats resulted in an increased mortality, neurological deficit and infarct volume of similar magnitude to lisinopril pretreatment. Coadministration of lisinopril 24 h before surgery completely blunted the protective effect of candesartan pretreatment. Administration of exogenous angiotensin IV (1 nmol) reversed the deleterious effect of lisinopril pretreatment. CONCLUSION:
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Authors | Sebastien Faure, Annabelle Bureau, Nicole Oudart, James Javellaud, Albert Fournier, Jean-Michel Achard |
Journal | Journal of hypertension
(J Hypertens)
Vol. 26
Issue 10
Pg. 2008-15
(Oct 2008)
ISSN: 0263-6352 [Print] England |
PMID | 18806625
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- AT4 receptor
- Angiotensin II Type 1 Receptor Blockers
- Benzimidazoles
- Biphenyl Compounds
- Receptor, Angiotensin, Type 2
- Receptors, Angiotensin
- Tetrazoles
- candesartan
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(pharmacology)
- Animals
- Benzimidazoles
(pharmacology)
- Biphenyl Compounds
- Brain Ischemia
(prevention & control)
- Disease Models, Animal
- Male
- Rats
- Rats, Sprague-Dawley
- Receptor, Angiotensin, Type 2
(drug effects, physiology)
- Receptors, Angiotensin
(drug effects, physiology)
- Tetrazoles
(pharmacology)
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