Dean Caron, Hillard Cecilia J, Seagard Jeanne L, Hopp Francis A, Hogan Quinn H
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin
Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
Am J Physiol Regul Integr Comp Physiol. 2016 Aug 1;311(2):R254-62. doi: 10.1152/ajpregu.00154.2016. Epub 2016 Jun 8.
The present study was undertaken to examine whether variations in endocannabinoid signaling in the dorsal periaqueductal gray (dPAG) are associated with baseline autonomic nerve activity, heart rate, and blood pressure. Blood pressure was recorded telemetrically in rats, and heart rate and power spectral analysis of heart rate variability were determined. Natural variations from animal to animal provided a range of baseline values for analysis. Transcript levels of endocannabinoid signaling components in the dPAG were analyzed, and endocannabinoid content and catabolic enzyme activity were measured. Higher baseline heart rate was associated with increased anandamide content and with decreased activity of the anandamide-hydrolyzing enzyme, fatty acid amide hydrolase (FAAH), and it was negatively correlated with transcript levels of both FAAH and monoacylglycerol lipase (MAGL), a catabolic enzyme for 2-arachidonoylglycerol (2-AG). Autonomic tone and heart rate, but not blood pressure, were correlated to levels of FAAH mRNA. In accordance with these data, exogenous anandamide in the dPAG of anesthetized rats increased heart rate. These data indicate that in the dPAG, anandamide, a FAAH-regulated lipid, contributes to regulation of baseline heart rate through influences on autonomic outflow.
本研究旨在探讨中脑导水管周围灰质背侧（dPAG）内源性大麻素信号的变化是否与自主神经活动基线、心率和血压相关。通过遥测技术记录大鼠的血压，并测定心率及心率变异性的功率谱分析。动物个体之间的自然差异为分析提供了一系列基线值。分析了dPAG中内源性大麻素信号成分的转录水平，并测量了内源性大麻素含量和分解代谢酶活性。较高的基线心率与花生四烯乙醇胺含量增加、花生四烯乙醇胺水解酶脂肪酸酰胺水解酶（FAAH）活性降低有关，且与FAAH和单酰甘油脂肪酶（MAGL，一种2-花生四烯酸甘油酯（2-AG）的分解代谢酶）的转录水平呈负相关。自主神经张力和心率与FAAH mRNA水平相关，但血压与之无关。根据这些数据，麻醉大鼠dPAG中的外源性花生四烯乙醇胺可使心率增加。这些数据表明，在dPAG中，FAAH调节的脂质花生四烯乙醇胺通过影响自主神经输出，有助于调节基线心率。
