Louis W J, Conway E L, Howes L G, Maccarrone C, Beart P M, Jarrott B
Department of Medicine and Clinical Pharmacology, Austin Hospital, Heidelberg, Victoria, Australia.
Can J Physiol Pharmacol. 1987 Aug;65(8):1633-7. doi: 10.1139/y87-256.
Studies of the roles played by neurotransmitters in the development of hypertension in the spontaneously hypertensive (SHR) rat are complicated by the presence of genetic differences between SHR and normotensive control rats, which are not related to differences in blood pressure. One approach that may be used in an attempt to overcome this difficulty is to study the manner in which neurotransmitter and metabolite levels change with age, and to relate these changes to alterations in blood pressure with ageing. Noradrenaline (NA) levels in the brainstem and spinal cord of SHR and Wistar Kyoto rats fell with age, while 3,4-dihydroxyphenylethyleneglycol (DHPG) levels (a neuronal metabolite of noradrenaline) remained constant. Similar changes were seen when NA and DHPG levels were measured in the discrete brainstem A1, A2, and C2 region, and when adrenaline, NA, and DHPG levels were examined in the C1 region. Differences in age-related changes of neuropeptide Y (NPY) levels were also found in the ventromedial nucleus of the hypothalamus and the locus coeruleus, and of beta-endorphin in the anterior hypothalamic nucleus, the paragigantocellular nucleus of the brainstem, and the locus coeruleus. These changes may indicate either a progressive increase in the activity of neurons in the sympathoexcitatory C1 region or a progressive reduction in the activity of vasodepressor A1, A2, and C2 regions with ageing, or both. However, changes in catecholamines and metabolites with age were similar in both strains and therefore cannot readily explain the more rapid rise in blood pressure with ageing in SHR rats.
在自发性高血压(SHR)大鼠中,研究神经递质在高血压发展过程中所起的作用较为复杂,因为SHR大鼠与正常血压对照大鼠之间存在遗传差异,而这些差异与血压差异无关。一种试图克服这一困难的方法是研究神经递质和代谢物水平随年龄变化的方式,并将这些变化与衰老过程中血压的改变联系起来。SHR大鼠和Wistar Kyoto大鼠脑干和脊髓中的去甲肾上腺素(NA)水平随年龄下降,而3,4 - 二羟基苯乙二醇(DHPG)水平(去甲肾上腺素的一种神经元代谢物)保持恒定。在离散的脑干A1、A2和C2区域测量NA和DHPG水平时,以及在C1区域检测肾上腺素、NA和DHPG水平时,也观察到了类似的变化。在下丘脑腹内侧核和蓝斑中,还发现了神经肽Y(NPY)水平与年龄相关变化的差异,以及在前下丘脑核、脑干巨细胞旁核和蓝斑中β - 内啡肽水平与年龄相关变化的差异。这些变化可能表明,随着年龄增长,交感兴奋的C1区域神经元活动逐渐增加,或者血管舒张的A1、A2和C2区域神经元活动逐渐减少,或者两者兼而有之。然而,两品系中儿茶酚胺和代谢物随年龄的变化相似,因此不能轻易解释SHR大鼠血压随年龄增长而更快升高的现象。