Glandular kallikreins are enzymes which release kinins, potent vasodilator peptides, from substrates called kininogens. They are found in the kidney, salivary gland, pancreas, intestine and sweat gland and in very high concentration in the exocrine secretion of these organs. Glandular kallikreins have been implicated in the regulation of electrolytes and water excretion, blood flow, blood pressure, and in the pathogenesis of hypertension. In order to further understand the possible functions of the glandular kallikrein-kinin system, we propose: 1) to develop a method to measure glandular kallikrein in plasma and then to determine its concentrations in different types of hypertension and other situations in which glandular kallikrein may play a physiological and pathological role, 2) to determine the precise localization of the different components of the kallikrein-kinin system in nephrons which have been separated by microdissection, 3) to determine the possible role of the renal kallikrein-kinin system in the regulation of renal function and blood flow, and to determine whether glandular kallikrein stimulates the release of renin """"""""in vivo,"""""""" independent of its kininogenase activity and hemodynamic effects, 4) to determine whether glandular kallikrein produced by salivary glands, pancreas and intestine plays a role in the regulation of blood flow of these organs and their function. The effect of oral administration of kallikrein will also be studied since it has been reported to have an antihypertensive effect, and 5) to identify and localize the components of the kallikrein-kinin system in the central nervous system (CNS) using highly specific methods which have been developed by us.
