The effect of the polymerized bovine haemoglobin solution, Hb-200, on endothelial function in isolated arterial rings from rats.
Haemoglobin-based oxygen carriers have been developed as 'blood substitutes'. Early cross-linked haemoglobins caused marked vasoconstriction, however, polymerized haemoglobin solutions, such as the bovine product haemoglobin glutamer-200 (bovine) (Hb-200), are said to have lesser vascular effects. The aim of this study was to quantify the effect of Hb-200 on isolated rat arterial rings. The actions of Hb-200 were investigated using rings of aorta and second-order mesenteric arteries from female Wistar rats. The arterial rings were mounted for isometric tension recording. Addition of Hb-200 (1 microM) to arterial rings, precontracted with phenylephrine (50-70% maximum phenylephrine-induced tone), resulted in vasoconstriction. Addition of Hb-200 to arteries precontracted with phenylephrine and relaxed with acetylcholine (1 microM) also caused contraction. Furthermore preincubation with Hb-200 (1 microM) enhanced the response to phenylephrine (1 nm to 10 microM) and impaired acetylcholine-induced relaxation (10 nm to 10 microM). Responses to Hb-200 were similar to those in response to the nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME, 100 microM), alone or in combination with Hb-200. These data demonstrate that Hb-200 has a significant vasoconstrictor effect similar to L-NAME. Thus the vascular actions of Hb-200 are consistent with activity as a NO scavenger. This may have implications for the clinical use of Hb-200.
Pawson
P
P
Veterinary Clinical Services, University of Glasgow Veterinary School, Glasgow, Scotland, UK.
Gibson
I F
IF
Dowell
F J
FJ
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001802:Blood Substitutes / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D001802:Blood Substitutes; D006454:Hemoglobins; D011108:Polymers; D014662:Vasoconstrictor Agents; C080663:polymerized bovine hemoglobin; D019331:NG-Nitroarginine Methyl Ester