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

100%

Faure S., Chapot R., Tallet D., Javellaud J., Achard J. M., Oudart N.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 3

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.

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Angiotensins II and IV modulate adrenocortical cell proliferation in ovariectomized rats

86%

Siejka A., Melen-Mucha G., Mucha S. A., Pawlikowski M.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 3

Effects of angiotensins II (AngII), angiotensin IV (AngIV, 3-8 fragment of angiotensin II) and losartan (an antagonist of angiotensin receptor type 1) on the proliferation of adrenocortical cells in ovariectomized rats have been studied. The incorporation of bromodeoxyuridine (BrdU) into cell nuclei was used as an index of cell proliferation. AngIV decreased BrdU labeling index mainly in the reticularis zone and losartan (Los) was able to partially reverse this inhibitory effect of AngIV. AngII had no effect on the adrenocortical cell proliferation when given alone, however Los given simultaneously diminished BrdU incorporation into nuclei of glomerulosa and reticularis zones as compared with AngII. These findings suggest that AngII and AngIV modulate adrenocortical cell proliferation in ovariectomized rats.

3

Angiotensin IV stimulates the activity of tyrosine kinases in rat anterior pituitary gland acting via AT1-like receptors?

72%

Rebas E., Lachowicz-Ochedalska A., Pawlikowski M.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 1,1

Angiotensin II (Ang II) is known to modulate tyrosine kinases (PTKs) activity in pituitary tumor cells. It is known that AngII is acting via AT1 receptors in many tissues. The aim of this study was to see whether 3-8 fragment of AngII, called angiotensin IV (AngIV) has a similar effect on tyrosine kinase activity in normal pituitary gland and what type of angiotensin receptor is involved in this process. The homogenates of normal rat pituitaries was a source of enzymes. The PTKs activity was determined using the synthetic substrate poly GluTyr and -32P-ATP. Ang IV was found to increase the PTK activity in the rat anterior pituitary tissue, with the maximal effect at concentration of 10-10M. AngII was ineffective at all concentrations studied. Losartan, a selective AT1 receptor blocker, added together with Ang IV abolished the effect of the latter, however losartan diminished also the PTK activity when applied together with Ang II, but only when it was added immediately before, but not after, the addition of Ang II. The involvement of a non-classic AT1-like receptor is suggested.

Ograniczanie wyników

3 Journal of Physiology and Pharmacology

2 Pawlikowski M.

1 Achard J. M.

1 Chapot R.

1 Faure S.

1 Javellaud J.

1 Lachowicz-Ochedalska A.

1 Melen-Mucha G.

1 Mucha S. A.

1 Oudart N.

1 Rebas E.

1 Siejka A.

1 Tallet D.

2 2006

1 2004

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

Angiotensins II and IV modulate adrenocortical cell proliferation in ovariectomized rats

Angiotensin IV stimulates the activity of tyrosine kinases in rat anterior pituitary gland acting via AT1-like receptors?