KALLIKREIN RELEASE BY VASCULAR TISSUE

Vascular tissue contains kallikrein and kallikrein mRNA, suggesting a vascular kallikrein-kinin system. We questioned whether 1) kallikrein concentration varies among large and small vessels; 2) kallikrein is released by vascular tissue; and 3) blocking protein synthesis inhibits release, suggesting de novo synthesis. Using rat vascular rings and isolated-perfused hindquarters, we examined kallikrein in the bath and perfusate. Active kallikrein was higher in tail arteries than the aorta (P < 0.001); tail veins had six times more kininogenase than the vena cava (P < 0.001). Total kallikrein showed a similar pattern, being highest in tail vessels. Arterial rings released active and total kallikrein. After 1, 2, and 3 h incubation, cumulative release was as follows: active, 90 +/- 13, 201 +/- 25, and 311 +/- 41 pg.h-1.mg tissue-1; total, 170 +/- 14, 366 +/- 24, and 537 +/- 40 pg.h-1.mg tissue-1, indicating constant release up to greater-than-or-equal-to 3 h. In contrast, lactic dehydrogenase fell from 6.7 +/- 2.5 to 2.5 +/- 0.4 U.h-1.mg tissue-1. Total kallikrein in the rings was 302 +/- 51 pg bradykinin/mg wt tissue before 3 h and 298 +/- 68 afterward. Kallikrein released by the hindquarters after 3 h was as follows: active, 6.2 +/- 2.8 ng bradykinin.min-1.kg body wt-1; total, 85.2 +/- 17 ng bradykinin.min-1.kg body wt-1. Puromycin pretreatment (10 mg ip) reduced total perfusate kallikrein from 105 +/- 19 to 8.5 +/- 3.6 (P < 0.005). Active kallikrein was undetectable. Thus kallikrein may be higher in small than in large vessels, while both arteries and veins synthesize and release kallikrein. Active kallikrein comprises between 10 (perfusate) and 40% (rings) of total kallikrein. Kinins generated locally by vascular kallikrein may help regulate vascular homeostasis.