CEREBRAL VASODILATING CAPACITY DURING FOREBRAIN ISCHEMIA - EFFECTS OFCHRONIC ESTROGEN DEPLETION AND REPLETION AND THE ROLE OF NEURONAL NITRIC-OXIDE SYNTHASE

Citation
Da. Pelligrino et al., CEREBRAL VASODILATING CAPACITY DURING FOREBRAIN ISCHEMIA - EFFECTS OFCHRONIC ESTROGEN DEPLETION AND REPLETION AND THE ROLE OF NEURONAL NITRIC-OXIDE SYNTHASE, NeuroReport, 9(14), 1998, pp. 3285-3291
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0959-4965
Volume
9
Issue
14
Year of publication
1998
Pages
3285 - 3291
Database
ISI
SICI code
0959-4965(1998)9:14<3285:CVCDFI>2.0.ZU;2-G
Abstract
THE effects of chronic 17 beta-estradiol (E-2) depletion, via ovariect omy (OVX), and its repletion, on cortical cerebral blood flow (CBF) an d EEG activities during forebrain ischemia, as well as post-ischemic r ecovery and neuropathology, were assessed and compared with results ob tained in normal female rats. We also examined whether neuronal nitric oxide synthase (nNOS) activity is affected by OVX and E-2 replacement and whether NOS-derived NO supports vasodilation during ischemia. OVX females displayed a significantly lower CBF during ischemia (10% of b aseline) than did normal females (23% of baseline). In OVX rats, given chronic low-dose E-2 treatment (0.1 mg kg(-1) day(-1)), intra-ischemi c CBF was similar to normal females (25% of baseline). However, at sup raphysiologic E-2 doses (greater than or equal to 0.5 mg kg(-1) day(-1 )), that benefit was diminished or lost. Intra-ischemic EEG power redu ctions and post-ischemic survival rates, neurological dysfunction, and histopathology displayed similar relative differences among groups as the CBF findings. Intra-ischemic CBF was reduced by nNOS inhibition, with ARL 17477, in normal and low-dose E-2-treated OVX rats (4-8% base line). The repressed intra-ischemic vasodilating function in OVX rats may be due to reductions in nNOS activity, because untreated OVX rats showed a 50% lower cortical nNOS activity than that in normal rats and in rats treated with low or high dose (5 mg kg(-1) day(-1)) E-2. Howe ver, the inability to restore vasodilating function despite normalizat ion of nNOS activity indicates that another mechanism is responsible f or the repression of vasodilatory function in the high-dose group. The se findings suggest that E,, at levels within the physiological range, promotes ischemic neuroprotection via improving vasodilating capacity . One possible mechanism may relate to E, enhancing brain nNOS express ion and activity. (C) 1998 Lippincott Williams & Wilkins.