The rostral ventrolateral medulla (RVLM) is the origin of a ¡§life-and-death¡¨ signal identifies from systemic arterial blood pressure spectrum that reflects failure of central cardiovascular regulation during brain stem death. It is also a target site where endogenous angiotensin II acts on angiotensin II type 1 receptors (AT1R) to increase blood pressure (BP); or on type 2 receptors (AT2R) to inhibit baroreceptor reflex (BRR) response. This study investigated the roles of AT1R and AT2R and their signaling pathways in RVLM for ¡§life-and-death¡¨ signal response during experimental brain stem death, using organophosphate mevinphos (Mev) as the experimental insult. In Sprague-Dawley rats, Mev (640 £gg/kg, i.v.) elicited an increase (pro-life phase) followed by a decrease (pro-death phase). Real-time PCR analysis revealed that whereas AT1R level underwent a 10% increase at pro-life phase, AT2R exhibited a significance increase of up to 40% at pro-death phase. Western blot analysis revealed that whereas AT1R level underwent a 20% increase at pro-life phase, AT2R exhibited a significant increase of up to 50% at pro-death phase. Pretreatment with microinjection of an AT1R antagonist losartan (2 nmol) into RVLM elicited abrupt death because of drastic hypotension through inhibiting NADPH oxidase and its downstream superoxide anion. Pretreatment with NADPH oxidase inhibitor DPI (1.5 nmol) inhibited NADPH oxidase avtiviting and superoxide anion production and decreased ¡§life-and-death¡¨ signal at pro-life phase; using superoxide anion inhibitor tempol (5 nmol) potentiated blood pressure and ¡§life-and-death¡¨ signal at pro-death phase. However, pretreatment with an AT2R antagonist PD123319 (2 nmol) potentiated the ¡§life-and-death¡¨ signal and antagonized hypotension during pro-death phase through inhibiting protein phosphotase 2A (PP2A) then activating extracellular signal-regulated kinase 1/2 (ERK1/2). Similar to AT2R antagonist PD123319, pretreatment with PP2A inhibitor okadaic acid (0.5 fmol) inhibit PP2A, leading to activation of ERK1/2, potentiate ¡§life-and-death¡¨ signal and antagonized hypotension during pro-death phase. These results suggest that AT1R in RVLM plays a ¡§pro-life¡¨ role through NADPH oxidase/superoxide anion during experimental brain stem death by maintaining BP and ¡§life-and-death¡¨ signal; AT2R plays a ¡§pro-death¡¨ role through PP2A/ERK1/2 by inhibiting BP and ¡§life-and-death¡¨ signal, and superoxide may also plays a ¡§pro-life and pro-death¡¨ role at pro-death phase.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0825109-123213 |
| Date | 25 August 2009 |
| Creators | Li, Ping-tao |
| Contributors | Julie Y.H. Chan, Alice Y.W. Chang, Samuel H.H. Chan |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0825109-123213 |
| Rights | campus_withheld, Copyright information available at source archive |
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