Role of adrenergic mechanisms in the pressor effect of diaspirin cross-linked hemoglobin.
Diaspirin cross-linked hemoglobin (DCLHB; Baxter Healthcare Corp., Blood Substitutes Division) is a promising hemoglobin-based oxygen-carrying resuscitative solution. DCLHb (400 mg/kg, intravenously) produces an immediate increase in blood pressure when administered to conscious or anesthetized rats. To determine the role of the central nervous system and the peripheral vascular system in the pressor effect of DCLHb, experiments were performed in cervical-sectioned rats. Intravenous administration of DCLHb produced an increase in blood pressure in cervical-sectioned animals (41.2 +/- 2.5 mm Hg), which was similar to that observed in normal rats. To test whether the pressor effect was due to release of catecholamines or other pressor substances from the adrenal medulla, DCLHb was administered to bilateral adrenal demedullated rats. DCLHb was found to produce a pressor effect in bilateral adrenal demedullated rats (42.0 +/- 6.4 mm Hg) that was similar to normal rats. To determine whether DCLHb alters the responsiveness of peripheral vascular adrenoceptors, the effect of DCLHb pretreatment on the blood pressure and heart rate responses of adrenergic agonists was studied. DCLHb significantly potentiated (66.7%) the pressor response to norepinephrine (0.5 to 2.0 microgram/kg, intravenously) but did not affect the heart rate response to norepinephrine. Phenoxybenzamine completely blocked the DCLHb-induced potentiation of the norepinephrine responses. Phenylephrine produced a dose dependent (5 to 20 micrograms/kg, intravenously) pressor and reflex bradycardic effect. DCLHb significantly potentiated the pressor (40.6%) and bradycardiac (-22.8%) effect of phenylephrine, which were completely blocked by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)
Gulati
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Department of Pharmaceutics and Pharmacodynamics (m/c 865), University of Illinois at Chicago 60612.
Rebello
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D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D006454:Hemoglobins; D010656:Phenylephrine; C083478:diaspirin-cross-linked hemoglobin; D003000:Clonidine; D001241:Aspirin; D009638:Norepinephrine