Diaspirin cross-linked hemoglobin (DCLHB): involvement of adrenergic mechanisms in the pressor effect.
Diaspirin cross-linked Hemoglobin (DCLHb) (400 mg/kg, i.v.), a resuscitative solution, produces a pressor effect in rats and several other species. Studies were conducted to determine the role of the central nervous system and adrenal medulla in the pressor effect of DCLHb in rats. Intravenous administration of DCLHb produced an increase in blood pressure in cervical sectioned animals, which was comparable to that observed in normal rats. This indicates that the pressor effect of DCLHb was mediated through the peripheral vascular system rather than through the central nervous system. DCLHb produced a pressor effect in bilateral adrenal demedullated rats that was similar to normal rats, suggesting that the pressor effect is not through the release of catecholamines or other pressor substance from the adrenal medulla. The effects of DCLHb pretreatment on norepinephrine (0.5 microgram/kg), phenylephrine (5 micrograms/kg) and clonidine induced blood pressure and heart rate responses were also studied. DCLHb significantly potentiated the pressor response to norepinephrine and phenylephrine. Clonidine normally produces a fall in blood pressure by acting on the central alpha-adrenoceptors, and a rise in blood pressure by stimulating the peripheral vascular alpha-adrenoceptors. DCLHb produced a marked potentiation of the pressor response to clonidine (75 micrograms/kg, i.v.), that masked the central depressor effect. The specificity of the potentiation was confirmed by using phenoxybenzamine, prazosin, and yohimbine. In order to exclude the contribution of a centrally induced cardiovascular effect of clonidine, further studies were carried out in cervical sectioned rats. DCLHb markedly potentiated the pressor effect of clonidine (25 micrograms/kg, i.v.) in cervical sectioned rats. This potentiation could be attenuated by prazosin and yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)
Gulati
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Department of Pharmacodynamics (m/c 865), University of Illinois at Chicago 60612-7231.
Rebello
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S
D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001802:Blood Substitutes / Q000008:administration & dosage / Q000494:pharmacology*; D003000:Clonidine / Q000008:administration & dosage; D004347:Drug Interactions; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000008:administration & dosage; D011224:Prazosin / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000008:administration & dosage
D001802:Blood Substitutes; D006454:Hemoglobins; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; C083478:diaspirin-cross-linked hemoglobin; D003000:Clonidine; D001241:Aspirin; D011224:Prazosin