Dominiak P, Simon M, Blöchl A, Brenner P
Institute of Pharmacology, Medical University of Lübeck.
Agents Actions Suppl. 1992;38 ( Pt 3):52-61.
Since converting enzyme and kininase II are identical enzymes and probably influences both, the biosynthesis of Ang II and the metabolism of bradykinin we investigated the effects of bradykinin, desArg-bradykinin and some bradykinin antagonists (desArg[9]-Leu[8]-bradykinin, HOE S 890307) on the sympathetic outflow of pithed SHR or Brown-Norway-Rats before and after acute or chronic inhibition of the converting enzyme by ramipril. bradykinin increased dose dependently the noradrenaline and adrenaline release in particular when the converting enzyme was inhibited. DesArg-bradykinin caused a dose-dependent increase in adrenaline release only after converting enzyme inhibition. The bradykinin-antagonists led to an increase in adrenaline release during ramipril administration. The weak but significant stimulation of adrenaline release by the bradykinin antagonists after converting enzyme inhibition might be due to unspecific actions on the adrenal medulla possibly induced by histamine release from mast cells.
由于转化酶和激肽酶II是同一种酶,且可能对血管紧张素II的生物合成和缓激肽的代谢均有影响,因此我们研究了缓激肽、去精氨酸缓激肽及一些缓激肽拮抗剂(去精氨酸[9]-亮氨酸[8]-缓激肽、HOE S 890307)对经雷米普利急性或慢性抑制转化酶前后的脊髓横断型自发性高血压大鼠(SHR)或布罗-挪威大鼠交感神经输出的影响。缓激肽可使去甲肾上腺素和肾上腺素释放呈剂量依赖性增加,尤其是在转化酶受到抑制时。去精氨酸缓激肽仅在转化酶抑制后才导致肾上腺素释放呈剂量依赖性增加。缓激肽拮抗剂在雷米普利给药期间可使肾上腺素释放增加。转化酶抑制后缓激肽拮抗剂对肾上腺素释放的微弱但显著的刺激作用可能是由于对肾上腺髓质的非特异性作用,可能是由肥大细胞释放组胺所诱导。