Investigation of the effects of a polymerised bovine haemoglobin solution on tension in isolated canine saphenous artery.
OBJECTIVE
To investigate the vasoconstriction induced by a polymerised bovine haemoglobin solution, Hb-200, in isolated canine arteries.


METHODS
Rings of canine saphenous artery, from euthanatized dogs, were mounted between stainless steel wires in Krebs' solution (95% O2 , 5% CO2 , 37°C) for isometric tension recording. Following incubation with Hb-200, cumulative concentration response curves to phenylephrine (vasoconstrictor) and acetylcholine (vasodilator) were investigated. Responses to acute addition of Hb-200 were also examined in pre-constricted or pre-dilated arteries. Responses were further studied in the presence or absence of the endothelium, inhibitors of endothelium-dependent vasodilation (L-NAME, charybdotoxin and apamin), an endothelin antagonist (BQ-788) and the antioxidant superoxide dismutase.


RESULTS
Incubation with Hb-200 (0·2 or 2 g/L) significantly enhanced phenylephrine-induced contraction (decreasing half maximal effective concentration, EC50 , P=0·0035) and inhibited acetylcholine-induced relaxation (increasing EC50 , P<0·0001). Acute addition of Hb-200 (0·2 or 2 g/L) significantly increased tension in pre-constricted arteries (P=0·0059) and reversed relaxation in pre-dilated arteries (P=0·0005). These acute responses were abolished in endothelium-denuded arteries and arteries incubated with L-NAME. Responses to Hb-200 were unaffected by incubation with charybdotoxin and apamin, BQ-788, or superoxide dismutase.


CONCLUSIONS
Low concentrations of Hb-200 enhance vasoconstriction in isolated canine saphenous artery, primarily by antagonism of nitric oxide. This effect may be detrimental in some dogs (e.g. those at risk of volume overload) but beneficial in others (e.g. those in septic shock).
School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH.
P
P
Pawson
F J
FJ
Dowell
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D018999:Charybdotoxin / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D006454:Hemoglobins; D009842:Oligopeptides; D010880:Piperidines; D011108:Polymers; C080663:polymerized bovine hemoglobin; D018999:Charybdotoxin; D010656:Phenylephrine; D001030:Apamin; C086539:BQ 788; D013482:Superoxide Dismutase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester