Gaudet E A, Godwin S J, Head G A
Baker Medical Research Institute, Victoria, Australia.
Am J Physiol. 1998 Oct;275(4):R1174-84. doi: 10.1152/ajpregu.1998.275.4.R1174.
In the present study, we examined the effect of blockade of the brain stem renin-angiotensin system on renal sympathetic baroreflexes and chemoreflexes in conscious rabbits and examined the role of central catecholaminergic pathways in these responses. Eleven rabbits underwent preliminary surgical instrumentation and pretreatment with central 6-hydroxydopamine (6-OHDA, 500 micrograms/kg) or ascorbic acid 6 wk before the commencement of the experiments. Baroreflex curves were determined under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after central administration of either Ringer solution, the ANG II receptor antagonist losartan (10 micrograms), or the angiotensin-converting enzyme inhibitor enalaprilat (500 ng) on separate days. Losartan increased the upper plateau and the range of the mean arterial pressure (MAP)-renal sympathetic nerve activity (RSNA) curve (79 and 78%, respectively) in intact rabbits, whereas this effect was not observed in 6-OHDA-pretreated rabbits. Hypoxia elicited an increase in resting RSNA (111% in intact rabbits and 74% in 6-OHDA-injected rabbits) and elevated the upper plateau of the RSNA-MAP curve in both groups (89% in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan and enalaprilat increased the RSNA upper plateau in intact rabbits but had no effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rate baroreflex curves were observed. Thus the effect of losartan to increase RSNA, particularly during hypoxia and baroreceptor unloading, being abolished by central noradrenergic depletion suggests that the endogenous ANG II which normally causes an inhibition of renal sympathetic motoneurons is dependent on the integrity of central catecholaminergic pathways.
在本研究中，我们检测了阻断脑干肾素 - 血管紧张素系统对清醒家兔肾交感压力反射和化学反射的影响，并检测了中枢儿茶酚胺能通路在这些反应中的作用。11只家兔在实验开始前6周接受了初步手术植入仪器，并预先给予中枢6 - 羟基多巴胺（6 - OHDA，500微克/千克）或抗坏血酸。在分别给予林格液、血管紧张素II受体拮抗剂氯沙坦（10微克）或血管紧张素转换酶抑制剂依那普利拉（500纳克）前后，于常氧和低氧（10% O₂ + 3% CO₂）条件下测定压力反射曲线。氯沙坦使完整家兔的平均动脉压（MAP）-肾交感神经活动（RSNA）曲线的上平台和范围增加（分别增加79%和78%），而在预先用6 - OHDA处理的家兔中未观察到这种效应。低氧使两组家兔的静息RSNA增加（完整家兔增加111%，6 - OHDA注射家兔增加74%），并使两组RSNA - MAP曲线的上平台升高（完整家兔升高89%，6 - OHDA注射家兔升高114%）。在低氧期间，氯沙坦和依那普利拉使完整家兔的RSNA上平台增加，但对预先用6 - OHDA处理的家兔无影响。未观察到对MAP - 心率压力反射曲线有影响。因此，氯沙坦增加RSNA的效应，特别是在低氧和压力感受器失负荷期间，被中枢去甲肾上腺素能耗竭所消除，这表明通常引起肾交感运动神经元抑制的内源性血管紧张素II依赖于中枢儿茶酚胺能通路的完整性。
