DIROFILARIA-IMMITIS - HEARTWORM INFECTION CONVERTS HISTAMINE-INDUCED CONSTRICTION TO ENDOTHELIUM-DEPENDENT RELAXATION IN CANINE PULMONARY-ARTERY

Heartworm (Dirofilaria immitis) infection alters the behavior of vascu lar endothelial cells in vivo and in vitro, with the potential, theref ore, to influence vascular function. Histamine, an autocoid implicated in the pathogenesis of parasitic and inflammatory diseases, is vasoac tive, and causes endothelium-dependent relaxation in some vascular bed s. Experiments were designed to determine if histamine is an endotheli um-dependent vasodilator in in vitro rings of canine pulmonary artery from heartworm and control dogs; to elucidate: the mechanisms involved in histamine vasoactivity; and to measure circulating levels of hista mine. Dose-response relationships to histamine were done in rings of c anine pulmonary artery from heartworm and control dogs, in the presenc e and absence of endothelial cells, the HI receptor blocker tripelenna mine. or the H2 receptor blocker cimetidine. Histamine caused a dose-d ependent constriction in control, that was not influenced by endotheli al cell removal. However, histamine caused an endothelium-dependent re laxation in heartworm pulmonary artery that was converted to constrict ion by endothelial cell removal. In heartworm, histamine relaxation wa s mediated by H2 receptors, but did not appear to involve nitric oxide or cyclooxygenase products. While diseases cause depression of endoth elium-dependent relaxation, this is the first report of a disease that changes a constriction response to an endothelium-dependent relaxatio n. (C) 1998 Academic Press.