Cabassi A, Vinci S, Quartieri F, Moschini L, Borghetti A
Laboratory of Clinical Physiology, Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy.
Hypertension. 2001 Feb;37(2 Pt 2):698-702. doi: 10.1161/01.hyp.37.2.698.
Certain forms of experimental hypertension are characterized by organ-specific alterations of catecholaminergic pathways. The purpose of this study was to evaluate, in the same awake and freely moving normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) before and after the development of arterial hypertension, the norepinephrine (NE) turnover and, in particular, the neuronal NE reuptake activity that ends its effects once released from nerve terminals, in subcutaneous adipose tissue and in skeletal muscle, whose sympathetic efferents are respectively independent or dependent from baroreflexes. Plasma and tissue interstitial NE and 3,4-dihydroxyphenylethylene glycol (DHPG), its major deaminated metabolite, were measured before and after blockade of NE reuptake by tissue perfusion of desipramine through microdialysis probes. Arterial pressure and plasma NE in SHR were similar to those in WKY at 5 weeks of age but increased at 16 weeks of age. In contrast, plasma DHPG was already higher in young SHR. Basal interstitial NE and DHPG were increased in both tissues of young and old SHR compared with age-matched WKY. Desipramine induced a higher rise of interstitial NE in SHR of both ages, with a lesser increase in the skeletal muscle of old compared with young SHR. These results indicate an increased NE turnover in prehypertensive and hypertensive SHR in both baroreflex-dependent and -independent tissues, not shown by plasma NE levels in young SHR. In the skeletal muscle, where sympathetic efferents are baroreflex dependent, the reduced interstitial NE reuptake contributes to the higher availability of interstitial NE for postsynaptic effects in old SHR.
某些形式的实验性高血压的特征是儿茶酚胺能通路的器官特异性改变。本研究的目的是在清醒且自由活动的正常血压Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）在动脉高血压发生前后，评估去甲肾上腺素（NE）的周转率，特别是神经元NE再摄取活性，该活性在从神经末梢释放后终止其作用，分别在皮下脂肪组织和骨骼肌中进行评估，其交感神经传出分别独立于或依赖于压力反射。在通过微透析探针进行地昔帕明组织灌注阻断NE再摄取之前和之后，测量血浆和组织间质中的NE以及其主要脱氨基代谢产物3,4-二羟基苯乙二醇（DHPG）。SHR在5周龄时的动脉压和血浆NE与WKY相似，但在16周龄时升高。相比之下，年轻SHR的血浆DHPG已经更高。与年龄匹配的WKY相比，年轻和老年SHR的两个组织中的基础间质NE和DHPG均升高。地昔帕明在两个年龄段的SHR中均引起间质NE的更高升高，与年轻SHR相比，老年SHR骨骼肌中的升高幅度较小。这些结果表明，在压力反射依赖性和非依赖性组织中，高血压前期和高血压SHR的NE周转率增加，而年轻SHR的血浆NE水平未显示出这种情况。在交感神经传出依赖于压力反射的骨骼肌中，间质NE再摄取的减少导致老年SHR中间质NE对突触后效应的可用性更高。
