Antonaccio M J, Kerwin L
Hypertension. 1981 May-Jun;3(3 Pt 2):I54-62. doi: 10.1161/01.hyp.3.3_pt_2.i54.
The present study was designed to examine the effects of treatment of SHR with captopril, teprotide, and saralasin on vascular and cardiac responses to sympathetic nerve stimulation and angiotensin I and II (AI, AII) and norepinephrine (NE). A single dose of captopril (10 mg/kg i.v. as well as 10 and 100 mg/kg p.o.) caused significant and marked inhibition of pressor responses to sympathetic nerve stimulation in pithed SHR but cardiac responses were unaffected. Pressor responses to AI were abolished but those to AII and NE were not significantly altered. Neither teprotide nor saralasin caused consistent inhibition of sympathetic responses despite total blockade of AI and AII response respectively. Selective inhibition of pressor but not cardiac responses to sympathetic nerve stimulation was obtained after 2 weeks, 3 and 6 months of daily oral doses of captopril. In addition, postjunctional pressor responses to AI, AII, and NE were also significantly inhibited by chronic captopril treatment. Infusion of AII, bilateral nephrectomy, or pretreatment with indomethacin alone in pithed SHR receiving captopril had no effect on the inhibition of pressor responses to sympathetic stimulation. However, the combination of pretreatment of indomethacin and infusion of AII completely restored sympathetic function in SHR receiving captopril. These studies suggest that captopril has a selective inhibitory effect on vascular responses to sympathetic nerve stimulation but not on cardiac responses. Moreover, this effect may have a prejunctional component since, after acute treatment, there is no inhibitory effect on responses to AII or NE. Since, under appropriate conditions, the inhibition can be reversed by AII infusion but not nephrectomy, it is suggested that this inhibition occurs at the vascular level by inhibition of local AII formation by captopril, a site not accessible to teprotide or saralasin.
本研究旨在探讨卡托普利、替普罗肽和沙拉新对自发性高血压大鼠（SHR）血管及心脏对交感神经刺激、血管紧张素I和II（AI、AII）以及去甲肾上腺素（NE）反应的影响。单次静脉注射卡托普利（10mg/kg）以及口服10mg/kg和100mg/kg可显著且明显地抑制断头SHR对交感神经刺激的升压反应，但对心脏反应无影响。对AI的升压反应被消除，但对AII和NE的反应无明显改变。尽管替普罗肽和沙拉新分别完全阻断了AI和AII反应，但均未持续抑制交感反应。每日口服卡托普利2周、3个月和6个月后，可选择性抑制对交感神经刺激的升压反应而非心脏反应。此外，长期卡托普利治疗还可显著抑制对AI、AII和NE的节后升压反应。在接受卡托普利的断头SHR中，输注AII、双侧肾切除或单独用吲哚美辛预处理对抑制交感刺激的升压反应均无影响。然而，吲哚美辛预处理与输注AII联合应用可完全恢复接受卡托普利的SHR的交感功能。这些研究表明，卡托普利对血管对交感神经刺激的反应具有选择性抑制作用，但对心脏反应无此作用。此外，这种作用可能有节前成分，因为急性治疗后，对AII或NE的反应无抑制作用。由于在适当条件下，这种抑制可通过输注AII逆转，但不能通过肾切除逆转，提示这种抑制是通过卡托普利抑制局部AII形成在血管水平发生的，而替普罗肽或沙拉新无法作用于该部位。
