The Role of Central Sympathetic Related Nuclei in Methamphetamine Induced Acute Hypertension

• Main Authors: Ya-Wen Wu, 吳雅雯
• Other Authors: Hsun-Hsun Lin
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/70426219738639401862

碩士 === 慈濟大學 === 整合生理暨臨床科學研究所 === 96 === Methamphetamine (MA) is a strongly addictive psychostimulant that not only affects the central neurobehaviour but also cause cardiovascular dysfunctions, including tachycardia, myocardial ischemia and hypertension. MA produces increase in blood pressure and the response of heart rate mainly via sympathetic nervous system. The rostral ventrolateral medulla (RVLM), a central sympathoactivating nucleus, and caudal ventrolateral medulla (CVLM), a central sympathoinhibitory nucleus, have been well known to be critical to the tonic and reflexive sympathetic regulation of arterial blood pressure. It suggests that the RVLM and CVLM may be relevant to the hypertension induced by MA. Glutamate is the primary neurotransmitter involved in the cardiovascular regulation in the central sympathetic-related nuclei. Results from many studies have revealed that phosphorylation of the ionotropic glutamate receptor- NMDA receptors (NMDARs) on the RVLM will increase the receptor function which leads to an increase in central sympathetic outflow resulting in acute hypertension. Our data showed that intracerebroventricular (i.c.v., 50, 150 and 500 nmol) or intraperitoneal (i.p., 2 and 10 mg/kg) administration of MA increased blood pressure in a dose-dependent manner in anesthetized and conscious rats, respectively. In the meanwhile, a significant increase in the level of Fos protein was found in the RVLM after administration of MA. The available data suggested that the RVLM might involve in the central command pathway of MA-induced acute hypertension. In addition, MA (2 and 10 mg/kg; i.p.) induced a significant increase in the expression of the phosphoserine 896 protein (regulated by PKC) on NR1 subunit in the RVLM. Microinjection of the selective protein kinase C (PKC) inhibitor bisindolymaleimide (BIM, 4 nmol) into the RVLM blocked MA-induced pressor effects in anesthetized rats. Our results suggest that MA induced cardiovascular toxicity, especially acute hypertension, is associated with the phosphorylation of NMDA receptor subunit NR1 by PKC in the RVLM, which leads to an increase in central sympathetic outflow causing acute hypertension.