A Local Kallikrein-Kinin System Is Present in Rat Hearts

It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsinactivatable) kallikrein into the medium (46±5 and 380±18 pg bradykinin/mg, respectively, after 1 hour and 78±6 and 654±14 pg bradykinin/mg after 2 hours, n=7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9±2.9 to 2.9±1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423±25 pg bradykinin/mg in nonincubated slices and 370±42 pg bradykinin/mg after 2 hours, P=NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78±6 to 22±4 pg bradykinin/mg and total kallikrein from 654±14 to 113±9 pg bradykinin/mg (P