Tissue kallikreins are highly restricted anzymes that generate kinins, potent vasodilator peptides, from kininogens. Kininogens are known to be present in plasma, lymph, and other biological fluids. We recently demonstrated that a glandular kallikrein-like enzyme is present in the tail arteries and veins of rats. We hypothesize that vascular kallikrein may play a role in the local regulation of vascular tone. To better understand the precise role of vascular kallikrein in circulatory homeostatis we propose: 1a) to determine if glandular kallikrein is present in vascular territories other than rat's tail and in species other than the rat, 1b) to study the cellular and subcellular localization of the enzyme; 2a) to determine if kallikrein can be released from the vessel's wall; 2b) to determine if there is local generation of kinins by vascular kallikrein; 2c) to study if the resistance of vascular territories found to contain kallikrein is affected by inhibitors of either kallikrein or kinins; 3) to determine if vascular kallikrein is synthesized locally by """"""""pulse chase"""""""" studies and by seeking mRNA encoding for kallikrein; and 4) to establish if kallikrein concentration in vascular tissue of rats with different models of hypertension differs from that of normotensive control rats. In addition, because kallikrein can induce contractions of the estrogenized rat uterus and release of arachidonic acid and PG12 from endothelial cells by mechanism(s) not involving kinins, we propose: 5) to establish if the direct effects of kallikrein are secondary to activation of phospholipases, arachidonic acid release and formation of bioactive arachidonic acid derivatives. These studies may lead to a better understanding of the role of vascular kallikrein in local regulation of vascular resistance.
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| Mindroiu, T; Carretero, O A; Scicli, A G (1987) T-kininogen in rat plasma after nephrectomy and other surgical traumas. Agents Actions Suppl 22:265-76 |
