- 作者: Alice Y.W. Chang Julie Y.H. Chan Fu-Jen Kao Chun-Ming Huang Samuel H.H. Chan
- 作者服務機構: Center for neuroscience, Departments of Biolongical Science and Physics, National sun Yat-sen University, department of Medical Education and Research, Kaohsiung veterans general Hospital, Neuroscience Group, change Gung University and Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
- 中文摘要: --
- 英文摘要: We evaluated the relationship between the toxicity in-duced by the organophosphate mevinphos (Mev) andinducible nitric oxide synthase (iNOS) in the rostral ven-trolateral medulla (RVLM), the medullary origin of sym-pathetic neurogenic vasomotor tone. Adult Sprague-Dawley rats that were anesthetized and maintained withpropofol were used. Laser scanning confocal microscop-ic analysis revealed colocalization of the M2 subtype ofmuscarinic receptors (M R) and iNOS immunoreactivityin RVLM neurons. Comicroinjection bilaterally of Mev(10 nmol) and artificial cerebrospinal fluid (aCSF) into theRVLM elicited a progressive decline in systemic arterialpressure (SAP) and heart rate. This was accompaniedduring phase 1 Mev intoxication by an increase in thepower density of the very high-frequency (VHF; 5-9 Hz),high-frequency(HF; 0.8-2.4 Hz), low-frequency (LF; 0.25-0.8 Hz) and very low-frequency (VLF; 0-0.25 Hz) compo-nents of SAP signals. Phase 2 exhibited a reversal of theVHF and VLF power to control levels and a further reduc-tion in the power density of both HF and LF componentsto below baseline. Hypotension and bradycardia pro-moted by Mev were significantly blunted on coadminis-tration into the RVLM of the selective iNOS inhibitorsS-methylisothiourea (250 pmol) or aminoguanidine(250 pmol). Not only was the augmented power densityof HF and LF components during phase 1 Mev intoxica-tion further enhanced, the reduced power of these twospectral components during phase 2 was appreciablyantagonized. On the other hand, the temporal changes inVHF and VLF power were essentially the same as withcoadministration of Mev and aCSF. We conclude that, asa cholinesterase inhibitor, Mev may induce toxicity vianitric oxide produced by iNOS on activation of the M Rby the accumulated acetylcholine in the RVLM.
- 中文關鍵字: --
- 英文關鍵字: Mevinphos intoxication. Inducible nitric oxide synthase. M2 muscarinic receptor. Rostral ventrolateral medula