Effect of arsenical drugs on in vitro vascular responses of pulmonary artery from heartworm-infected dogs.
OBJECTIVE
To test the effect of thiacetarsamide and melarsomine on vascular responses in isolated rings of pulmonary artery from heartworm-infected dogs.


METHODS
18 heartworm-infected dogs.


METHODS
Isolated rings of pulmonary artery from heartworm-infected dogs were randomly treated with thiacetarsamide (30 micrograms/ml) or melarsomine dihydrochloride (30 micrograms/ml) for 30 minutes; untreated rings from the same dog served as control. Cumulative dose-response relations to norepinephrine, nitroglycerin, and methacholine were determined.


RESULTS
Norepinephrine-induced constriction was not altered by treatment with either thiacetarsamide or melarsomine. Treatment with thiacetarsamide depressed nitroglycerin-induced relaxation, compared with values for untreated control rings and rings treated with melarsomine. Treatment of rings with thiacetarsamide or melarsomine depressed methacholine-induced relaxation, compared with values for untreated rings. Histologic examination of rings indicated that treatment with thiacetarsamide or melarsomine resulted in loss of endothelial cells.


CONCLUSIONS
Endothelial cell loss as a direct drug effect may be responsible for impaired endothelium-dependent relaxation in pulmonary artery from heartworm-infected dogs. Thiacetarsamide appears to have additional effects on vascular smooth muscle, which may explain why fewer complications are observed in dogs treated with melarsomine.


CONCLUSIONS
Melarsomine may be a safer drug than thiacetarsamide and could be a better treatment for dogs with heartworm infection.
Maksimowich
D S
DS
Department of Physiology, Michigan State University, East Lansing 48824-1101, USA.
Bell
T G
TG
Williams
J F
JF
Kaiser
L
L
D000818:Animals; D001148:Arsenamide / Q000494:pharmacology* / Q000627:therapeutic use; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D004183:Dirofilaria immitis / Q000302:isolation & purification; D004184:Dirofilariasis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D004283:Dog Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D005260:Female; D005369:Filaricides / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000469:parasitology / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000469:parasitology / Q000502:physiology; D011897:Random Allocation; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001152:Arsenicals; D005369:Filaricides; D014227:Triazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016210:Methacholine Chloride; C076253:melarsomine; D005996:Nitroglycerin; D001148:Arsenamide; D009638:Norepinephrine