DPAVP - VASOPRESSIN ANALOG WITH SELECTIVE MICROVASCULAR AND RES ACTIONS FOR TREATMENT OF CIRCULATORY SHOCK IN RATS

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. Maximal concentrations of DPAVP narrow but do not occlude both arterioles and venules. Microscopic muscular venules (31-39 .mu. i.d. [inside diameter]) do not narrow more than 20% in response to DPAVP; and terminal arterioles (17-23 .mu. i.d.) do not narrow more than 50%. Systemic administration of DPAVP to rats subjected to hemorrhage or bowel ischemia shock 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. Administration of DPAVP i.v. returns arterial hematocrit towards normal after shock; it also regenerates and sustains vasomotion and venular tone, decreases microvascular hyperreactivity characteristic 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. DPAVP effectively restores the early RES phagocytic depression, characteristic of shock syndromes, to normal, the latter eventuating in RES hyperphagocytic activity. It is possible to synthesize vasoactive molecules which exert selective microvascular and RES phagocytic effects and are highly beneficial in the therapy of low-flow states, at least in rats.