Depression of endothelium-dependent relaxation by filarial parasite products.
Endothelium-dependent relaxation is depressed in the femoral artery of dogs with heartworm, Dirofilaria immitis, infection. Moreover, in infected dogs, the mechanism of relaxation is different. Because D. immitis is located primarily in the pulmonary circulation, these findings suggested that D. immitis releases biologically active mediators that alter distal endothelium-dependent relaxation. We tested this hypothesis in vitro. Rings of rat aorta were exposed to D. immitis (alone, in 1,000 mol wt or 100 mol wt cutoff dialysis tubing, and bioassay with conditioned medium). D. immitis alone depressed relaxation to acetylcholine, carbachol, and A23187. Nitroglycerin relaxation was not affected. Depression of acetylcholine relaxation was seen with D. immitis alone, in 1,000 mol wt dialysis tubing, and bioassay with conditioned medium. However, acetylcholine relaxation with D. immitis in 100 mol wt dialysis tubing was not different from control. It appears that D. immitis releases a small, stable, biologically active factor that alters endothelium-dependent relaxation. Its exact nature is unknown. The study of endothelial cell behavior in filariasis and modulation of endothelial cell function by filarial factors may provide important clues in understanding the pathogenesis of parasitic diseases.
Kaiser
L
L
Department of Physiology, Michigan State University, East Lansing 48824-1101.
Tithof
P K
PK
Williams
J F
JF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003956:Dialysis / Q000295:instrumentation; D004183:Dirofilaria immitis / Q000378:metabolism*; D004184:Dirofilariasis / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005370:Filarioidea / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D000001:Calcimycin; D002217:Carbachol; D005996:Nitroglycerin; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin