Elghozi J L, Head G A
Baker Medical Research Institute, Prahran, Victoria, Australia.
Am J Physiol. 1990 Jan;258(1 Pt 2):H240-6. doi: 10.1152/ajpheart.1990.258.1.H240.
We have investigated the contribution of spinal noradrenergic (NA) pathways to the central pressor effects of angiotensin II (ANG II) in conscious rabbits with intact baroreceptors and after sinoaortic denervation (SAD). Very low intracisternal (ic) doses of ANG II [half maximum dose (ED50) = 6 x 10(-15) mol] produced increases in mean arterial pressure (MAP) and decreases in heart rate. Pressor responses to intracisternal ANG II were markedly reduced by 100 pmol of the ANG II antagonist [( Sar1, Ile8] ANG II, ic) and by intravenous prazosin, suggesting that central activation of ANG II receptors increased sympathetic vasoconstrictor tone. After SAD, the rabbits exhibited a 900-fold increase in sensitivity to ANG II (i.e., responded to very much lower doses, ED50 = 5 x 10(-18) mol). Intraspinal 6-hydroxydopamine (6-OHDA) injections given 1 mo earlier did not alter dose-response curves in baroreceptor-intact rabbits. However, the SAD-induced increase in sensitivity to ANG II was not observed in rabbits with depletion of spinal NA pathways. The results suggest intracisternal administration of ANG II activates two functionally distinct pathways: 1) a very sensitive site that utilizes NA projections to the spinal cord, and 2) a less sensitive site that uses non-NA descending pathways. Under normal baroreceptor input the former pressor pathway is completely inhibited. Thus the role of the central renin-angiotensin system may be of greater physiological importance in conditions where the baroreflex is suppressed.
我们研究了脊髓去甲肾上腺素能（NA）通路在有意识的、压力感受器完整的家兔以及在去窦主动脉神经（SAD）后，对血管紧张素II（ANG II）的中枢升压作用的贡献。极低的脑池内（ic）剂量的ANG II [半数最大剂量（ED50）= 6×10⁻¹⁵摩尔] 可使平均动脉压（MAP）升高并使心率降低。对脑池内ANG II的升压反应被100皮摩尔的ANG II拮抗剂[（Sar1，Ile8）ANG II，ic]和静脉注射的哌唑嗪显著降低，这表明ANG II受体的中枢激活增加了交感缩血管张力。在SAD后，家兔对ANG II的敏感性增加了900倍（即对低得多的剂量有反应，ED50 = 5×10⁻¹⁸摩尔）。1个月前进行的脊髓内6-羟基多巴胺（6-OHDA）注射并未改变压力感受器完整的家兔的剂量-反应曲线。然而，在脊髓NA通路耗竭的家兔中未观察到SAD诱导的对ANG II敏感性增加。结果表明，脑池内给予ANG II激活了两条功能不同的通路：1）一个非常敏感的位点，它利用向脊髓的NA投射；2）一个不太敏感的位点，它使用非NA下行通路。在正常压力感受器输入下，前一个升压通路被完全抑制。因此，在压力反射被抑制的情况下，中枢肾素-血管紧张素系统的作用可能具有更大的生理重要性。
