Recombinant human hemoglobin (rHb1.1) selectively inhibits vasorelaxation elicited by nitric oxide donors in rabbit isolated aortic rings.
We investigated the effect of a genetically engineered recombinant human hemoglobin (rHb1.1), specially designed to be used as a blood substitute, on the ability of various well-known vasodilators to relax the rabbit isolated aortic rings precontracted with the alpha-adrenoceptor agonist phenylephrine (PE) or with KCl (for nifedipine only). The vasorelaxant effects of nitroglycerin (NTG) and of sodium nitroprusside (SNP), two nitrovasodilators whose effects are mediated by nitric oxide (NO), were inhibited in a concentration-dependent manner by rHb1.1 (1.5 and 15 microM). Those elicited by isoproterenol, papaverine, histamine, adenosine, atriopeptin II, hydralazine, nifedipine, and cromakalim were comparatively little affected or not affected by rHb1.1 (15 microM). The ability of captopril to inhibit the vasoconstrictor action of angiotensin I (AT1) in the rabbit aortic rings was not reduced by rHb1.1 (15 microM). Our results suggest that rHb1.1 shares with purified human Hb the ability to inhibit selectively the vasorelaxant effect of NO-releasing substances such as NTG and SNP. Because the targeted plasma concentration of rHb1.1, when used as a blood substitute, is greater (approximately 50 times) than the highest concentration of rHb1.1 used in this study, significant drug interactions can be predicted between NO donors and rHb1.1.
Rioux
F
F
Centre de Recherche (Université Laval) de L'Hôtel-Dieu de Quebec, Canada.
Drapeau
G
G
Marceau
F
F
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D006454:Hemoglobins; D011994:Recombinant Proteins; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000803:Angiotensin I; D002216:Captopril; D005996:Nitroglycerin; D011188:Potassium