Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis.

Abstract

A role for altered endothelial cell function is emerging in the pathogenesis of disease. We have previously demonstrated that Dirofilaria immitis, the canine heartworm, depresses endothelium-dependent responses and alters the mechanism of relaxation in the in vivo femoral artery of infected dogs. Exposure of rat aorta to the parasite or parasite-conditioned medium selectively depresses endothelium-dependent relaxation. D. immitis is closely related to the major human filarial pathogens. This study was designed to examine the effect of chronic infection with the filarial nematode Brugia pahangi on endothelium-mediated responses of the rat aorta in vitro. We tested the hypothesis that endothelium-dependent responses are depressed in the aorta from rats infected with B. pahangi. Rings of thoracic and abdominal aorta were suspended in muscle baths for measurement of isometric tension. Dose-response relations to norepinephrine, endothelium-dependent dilators (acetylcholine, histamine, and A23187), and nitroglycerin were done. In some experiments, inhibitors of cyclooxygenase (indomethacin and aspirin), guanylate cyclase (methylene blue), and nitric oxide formation (N-nitro-L-arginine methyl ester; L-NOARG) were used. No differences in vascular reactivity were detected in the thoracic aorta. In contrast, endothelium-dependent responses in abdominal aorta of Brugia-infected rats were significantly depressed when compared with control aorta from noninfected rats. Acetylcholine relaxation was further depressed by indomethacin and aspirin. After L-NOARG, acetylcholine relaxation in control abdominal aorta was completely abolished; however, in abdominal aorta of Brugia-infected rats, acetylcholine still caused relaxation. Methylene blue inhibited acetylcholine relaxation in both control and Brugia-infected abdominal aorta; however, relaxation in Brugia-infected aorta was significantly greater than control. This study demonstrates that endothelium-dependent relaxation can be altered by chronic experimental filarial infection in the absence of direct contact between the blood vessel and the parasite. The mechanism of relaxation in the Brugia-infected abdominal aorta appears to be altered when compared with control, suggesting that parasites are capable of modulating vascular reactivity by inducing changes in endothelial cell behavior. The mechanism may involve parasite-induced local inflammation or alterations in endothelial cell metabolism. Understanding how chronic experimental filarial infection alters vascular reactivity may enhance our understanding of the pathogenesis of human filariasis.

Effect of Brugia malayi on the Growth and Proliferation of Endothelial Cells In vitro

“…Filarial products also alter the physiological function of endothelial cells (Kaiser et al, 1991). The results from our in vitro studies using indomethacin or BW 775Hcl suggest that the parasite-derived prostanoid or cyclooxygenase products alone may not inhibit the proliferation of endothelial cells.…”

Role of nitric oxide in parasitic infections.

“…Depressed endothelium-dependent relaxation has been described in canine Dirofilaria immitis (heartworm) infection and in lymphatic filariasis (78,79). In D. immitis infection, this appears to be due to a released parasite product and can be duplicated by serum from infected dogs (93).…”

Heartworm extract induces relaxation of isolated rat thoracic aorta

“…Structural analogues of L-arginine, such as L-NAME, are the most specific inhibitors of NO synthase [7, 15]. Inhibition by these analogues is specifically reversed by L-arginine [7, 15].…”

“…Inhibition by these analogues is specifically reversed by L-arginine [7, 15]. Complete inhibition of LC extract-induced relaxation by L-NAME and restoration of the effect with L-arginine, suggested that the response of the thoracic aorta is mediated entirely by NO.…”