New data are providing additional support for the hypothesis that the renal (and glandular) kallikrein-kinin system is involved in electrolyte homeostasis, renal function and the control of systemic arterial pressure. The data include: further correlations amongst urinary kallikrein, blood pressure, race, and other variables in children of normal or hypertensive parentage; more information about system components and activity in normal subjects, patients with hypertensive and other diseases, and in certain animal models; newly discovered relations between the system, other systems important to renal and cardiovascular homeostatic events, drugs and membrane ion transport; additional histochemical and biochemical data on system component localization and regulation; and major advances in measurement technology. The research will explore relations amongst the kallikrein-kinin system, membrane ion transport, aldosterone and systemic blood pressure. We shall examine: factors which regulate kallikrein synthesis and activity; the role of the system in membrane ion transport; the effects of drugs, biochemicals and disease which alter adrenal/renal function and/or blood pressure upon the system, and conversely, the effects of altered system activity upon electrolyte transport, excretion and blood pressure. Active and inactive kallikreins, kinins and kininogens will be measured with radioimmuno-, radio-chemical, spectrophotometric and bioassays. Selected components of the cyclooxygenase cascade, cyclic nucleotides and calcium will be measured in studies designed to examine the biochemical events related to the functional responses to kallikrein and kinins. Normal volunteers, patients with hypertensive and other diseases as well as isolated tissues and cells will be studied. Our objecties are: 1) to continue to define factors which regulate the activity of the glandular (renal) kallikrein-kinin system; 2) to continue to describe the function of the glandular (renal) kallikrein-kinin system; 3) to continue to assess the role of the system in hypertensive diseases; and 4) to understand the mechanisms responsible for the kallikrein-aldosterone relationship.
