Dirofilaria immitis: heartworm infection alters pulmonary artery endothelial cell behavior

Abstract

The pathogenesis of filariasis has generally been attributed to either physical presence of the adult parasites or the host's immune response to the parasites. However, the spectrum of filariasis cannot be entirely explained by these causes, and other mechanisms must be operative. It is now evident that factors released by filarial parasites likely contribute to the pathogenesis of filarial diseases. Adult heartworms (Dirofilaria immitis) reside in the right heart and pulmonary artery, so the pulmonary artery should be exposed to the highest concentration of filarial factors. We tested the hypothesis that endothelium-dependent relaxation is altered in the in vitro pulmonary artery from heartworm-infected dogs. Relaxation responses to endothelium-dependent vasodilators (methacholine, bradykinin, substance P, and A-23187) and the nonendothelium-dependent vasodilator nitroglycerin and contractile responses were measured in rings of pulmonary artery from control and heartworm-infected dogs. Endothelium-dependent relaxation was assessed in the presence and absence of inhibitors of nitric oxide synthase, cyclooxygenase, and guanylate cyclase. Responses to methacholine, substance P, and A-23187, but not to bradykinin, nitroglycerin, norepinephrine, or KCl, were depressed in pulmonary artery from heartworm-infected dogs when compared with control, suggesting that changes in endothelial cell and not vascular smooth muscle behavior are involved in altered relaxation. The mechanism of endothelium-dependent relaxation in control pulmonary artery appears to involve nitric oxide in the case of methacholine and both nitric oxide and a cyclooxygenase product in the case of bradykinin and A-23187. The mechanism of endothelium-dependent relaxation in pulmonary artery from heartworm-infected dogs was not clearly elucidated. These data provide no evidence that heartworm infection globally influences either endothelial cell receptor function or the vascular smooth muscle guanylate cyclase guanosine 3',5'-cyclic monophosphate system, making it likely that changes in intracellular signaling are primarily responsible for the observed alteration of endothelium-mediated relaxation. Alteration of endothelial cell function by filarial parasites may be an important component in the pathology associated with filariasis.

Manipulation of vascular function by blood flukes?

“…A complication is that worms secrete the heme-containing metabolite hemozoin as a waste product of hemoglobin digestion 36 and it is known that heme products can inactivate NO 37–39 . It is noteworthy that infection with the vascular nematode parasite Dirofilaria immitis can lead to an alteration in the relaxation behavior of endothelial cells of the pulmonary artery, and NO has been implicated in this effect 40 .…”

Thromboembolic Conditions, Aetiology Diagnosis and Treatment in Dogs and Cats

“…In contrast, other authors described that the endothelial cell is a more likely target of the parasite, since the heartworm infection does not influence the vascular tone of the pulmonary artery. Dirofilaria immitis (DI) infection does not cause a complete depression of endothelial cell function, but rather selectively alters endothelial cell behaviour (Mupanomunda et al 1997). Moreover, when the vascular endothelium is exposed to higher doses of the DI antigen with subsequent adulticide treatment, there is an increased expression of enzymes responsible for the synthesis of NO, eNOS and iNOS and the increased synthesis of the eicosanoids related to inflammation such as COX-2, 5-LO, PGE2 and LTB4 (Morchón et al 2008).…”

Nitric oxide production and nitric oxide synthase immunoreactivity in Naegleria fowleri

“…A recent report has provided evidence for the existence of multiple NOS genes in fish and echinoderms, showing the appearance of multiple forms early in chordate evolution (Cox et al 2001). Whereas there are reports of NO production by certain insect species (Weiske and Wiesner 1999), mollusks (Huang et al 1997;Moroz et al 1996;Sanchez-Alvarez et al 1994), and nematodes such as Ascaris suum, Dirofilaria immitis, and Brugia species (Bascal et al 1996;Kaiser et al 1998;Mupanomunda et al 1997;Pfarr and Fuhrman 2000), the information about the production of this molecule by protozoa is limited. Nevertheless, the erythrocyte stage of Plasmodium falciparum displays a high NOS activity, (Ghigo et al 1995).…”