Cerebroprotective effect of angiotensin IV in experimental ischemic stroke in the rat mediated by AT4 receptors

• Autorzy: Faure S. , Chapot R. , Tallet D. , Javellaud J. , Achard J.M. , Oudart N.
• Języki publikacji: EN

Abstrakty

EN

Recent studies have reported potential roles of angiotensins in an adaptative physiological mechanism of protection against cerebral ischemia-induced neurological damages. In the present study, we examined the protective role of angiotensin IV (AngIV) in a rat model of embolic stroke induced by intracarotid injection of calibrated microspheres (50 µm). Internal carotid infusions of increasing doses of AngIV (0.01, 0.1 and 1 nmol/0.1 mL saline) dose dependently decreased mortality, neurological deficit and cerebral infarct size at 24 hours. With the highest dose of AngIV, mortality was reduced from 55 % in saline infused controls to 10 % (p=0.003), neurological deficit was reduced from 3.8 ± 0.3 to 1.4 ± 0.3 , (p<0.0001) and cerebral infarct size at 24 hours was decreased from 432 ± 26 mm3 to 185 ± 19, (p=0.0001). The AT4 antagonist divalinal-AngIV (10-9 mol/0.1 mL), or pretreatment with L-NAME (10-7 mol/0.1 mL), both completely abolished the protective effect of AngIV (1 nmol). The AT2 antagonist PD123319 (10-7 mol/0.1 mL) partially prevented the protective effect of AngIV on the neurological score. Sequential cerebral arteriographies revealed that AngIV induced a redistribution of blood flow to the ischemic areas within minutes. These results suggest that pharmacological doses of AngIV are protective against acute cerebral ischemia by triggering an AT4-mediated, NO-dependent intracerebral hemodynamic mechanism.

Słowa kluczowe

EN

AT4 receptor; ischaemic stroke; renin-angiotensin system; rat; angiotensin IV

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2006
• Tom: 57
• Numer: 3
• Opis fizyczny: p.329-342,fig.,ref.

Twórcy

autor

Faure S.

• Universite de Limoges, 2 rue du Docteur Marcland, 87025 Limoges, France

autor

Chapot R.

autor

Tallet D.

autor

Javellaud J.

autor

Achard J.M.

autor

Oudart N.