Increased Levels of New Spasmogenic Substances Released by Trypsin from Plasma of Hypertensive Rats

SUMMARY The present study was undertaken to evaluate the participation of the kallikrein-kinin system in the normalization of blood pressure after release of the clip in one-kidney, one clip hyperten-sive rats (1K1C). Kininogen was determined before and after unclipping by tryptic digestion of denatured rat plasma, and spasmogenic activity was measured with isolated guinea pig ileum. In contrast to human plasma for which bradykinin (BK) is the only trypsin-releasable spasmogenic substance (TRSS), rat plasma contains non-BK TRSS (Fractions P, and P2) as well as BK. Fractions Pi and P2 were separated from BK by SP-Sephadex chromatography. An increase of total TRSS was demonstrated 60 days after clipping and reached a maximum at approximately Day 75, which was two times that of the normotensive controls (NC). The level of total TRSS did not change after unclipping. The increased level of TRSS in the hypertensive state confirmed the observations of other investiga-tors who reported increased kininogen levels but who could not distinguish between BK and non-BK TRSS because bioassays were performed without prior chromatographic separation of the spasmo-genic activities. Fractions Pi and P2 were present in the TRSS of both 1K1C and NC plasma, but were two to six times higher in 1K1C and thus probably accounted quantitatively for the increased TRSS in 1K1C. The data suggest that in the hypertensive state there is an alteration in the relative amounts o