A comparison of the effects of angiotensin-converting enzyme inhibitors with bradykinin, angiotensin II and their specific antagonists on concanavalin A-induced proliferation of mouse T-lymphocytes.

The effects of the angiotensin-converting enzyme (ACE) inhibitors captopril, enalaprilat and enalapril, and the bioactive peptides angiotensin II (Ang II), [Sar1,Ile8]angiotensin II ([Sar1,Ile8]Ang II), bradykinin and D-Arg[Hyp3,D-Phe7]bradykinin) on mitogen-induced proliferation of T-lymphocytes were evaluated in C57 mouse spleen cells. Captopril (CP) dose-dependently enhanced concanavalin A (Con A)-induced proliferation of T-lymphocytes, with the effective stimulatory concentration range between 0.02-10 mM. The mitogen-induced proliferative response was inhibited at high concentrations (> 10 mM) of CP which affected the number of viable cells. Enalapril dose-dependently inhibited Con A-induced T-lymphocyte proliferation at 0.44-20 mM. This was comparable to the ACE inhibitory peptide, which had a similar range. Enalaprilat, the active parent diacid of enalapril, also showed a weaker inhibitory effect on the Con A-induced proliferative response (4-20 mM). The bioactive peptides had little effect, except at a relatively high concentration. Angiotensin II (Ang II) at 0.05 mM inhibited the Con A-induced proliferative response while [Sar1,Ile8]Ang II, a specific antagonist of Ang II, had no effect. Both bradykinin and its specific antagonist, D-Arg[Hyp3,D-Phe7]bradykinin, had no effect on Con A-induced T-lymphocyte proliferation. The ACE inhibitors and bioactive peptides had little or no cytotoxic effects, except when present at or more than 5 mM. In conclusion, the effects of ACE inhibitors such as captopril and enalapril on Con A-induced T-lymphocyte proliferation were confirmed after a pilot study recently reported. These effects, especially with the stimulatory effect of CP, are unrelated to their ability to inhibit angiotensin-converting enzyme and perturbation of the bioactive peptides such as angiotensin II and bradykinin.