DPAVP: A vasopressin analog with selective mcirovascular and res actions for the treatment of circulatory shock in rats

Abstract

The present study indicates that: (a) local administration of low concentrations of an analog of vasopressin, 1-deamino-[2-phenylalanine, 8-arginine]-vasopressin (DPAVP), constricts venules in the rat splanchnic terminal vascular bed of normal animals, unlike that seen for catecholamines; (b) maximal concentrations of DPAVP narrow but do not occlude both arterioles and venules; (c) microscopic muscular venules (31–39 μ i.d.) do not narrow more than 20% in response to the vasopressin analog DPAVP; and (d) terminal arterioles (17–23 μ i.d.) do not narrow more than 50% in response to DPAVP. Systematic administration of DPAVP to rats subjected to hemorrhage or bowel ischemiashock more than doubles survival rates over control rats receiving Ringer solution. Infusion of DPAVP produces a dose-dependent effect on arterial blood pressure, microscopic capacitance vessels, large arterioles and small arteries. In addition, i.v. administration of DPAVP: (a) returns arterial hematocrit towards normal after shock; and (b) regenerates and sustains vasomotion and venular tone, decreases microvascular hyperreactivity characteristics of shock syndromes, restores constricted arteriolar lumen sizes towards normal, predisposes to a splanchnic microbed virtually free of stasis, petechiae and leukocytic sticking, and restores capillary perfusion and outflow to near-normal. Further, DPAVP effectively restores the early reticuloendothelial system (RES) phagocytic depression, characteristic of shock syndromes, to normal; the latter eventuating in RES hyper-phagocytic activity. These findings indicate it is possible to synthesize vasoactive molecules which: (a) exert selective microvascular and RES phagocytic effects; and (b) are highly beneficial in the therapy of low-flow states, at least in rats.