Wada T, Aoyagi T, Iinuma H, Ogawa K, Kojima F, Nagai M, Kuroda H, Obayashi A, Takeuchi T
Institute of Microbial Chemistry, Tokyo, Japan.
Biotechnol Appl Biochem. 1988 Oct;10(5):435-46.
It was previously shown that autoregressive modeling can be used for feedback analysis in the body. We used this method to investigate the dynamic changes in and around the renin-angiotensin system in vivo induced by angiotensin-converting enzyme (ACE) inhibition. Long-term studies were performed on rabbits, which were given a daily injection of one of the following ACE inhibitors: captopril, foroxymithine, or histargin. For comparison, other rabbits received injections of saline or the renin inhibitor pepstatin. Autoregressive coefficients were computed from the raw data thus observed and were used to simulate the impulse-response function proper to each animal. The response of each animal estimated in this way exposed the effects of ACE inhibitors in vivo which were obscured by the feedback regulation of the renin-angiotensin system. Also, it was suggested that histargin has a peculiar action, blocking the negative feedback that would be elicited by the usual ACE inhibition. Feedback analysis seems to be essential to elucidate the in vivo effects of enzyme inhibitors.
