DIASPIRIN CROSS-LINKED HEMOGLOBIN (DCLHB(TM)) - INVOLVEMENT OF ADRENERGIC-MECHANISMS IN THE PRESSOR EFFECT

Diaspirin cross-linked Hemoglobin (DCLHb(TM)) (400 mg/kg, i.v.), a resuscitative solution, produces a presser effect in rats and several other species. Studies were conducted to determine the role of the central nervous system and adrenal medulla in the presser 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 presser effect of DCLHb was mediated through the peripheral vascular system rather than through the central nervous system. DCLHb produced a presser effect in bilateral adrenal demedullated rats that was similar to normal rats, suggesting that the presser effect is not through the release of catecholamines or other presser substance from the adrenal medulla. The effects of DCLHb pretreatment on norepinephrine (0.5 mu g/kg), phenylephrine (5 mu g/kg) and clonidine induced blood pressure and heart rate responses were also studied. DCLHb significantly potentiated the presser 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 presser response to clonidine (75 mu g/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 presser effect of clonidine (25 mu g/kg, i.v.) in cervical sectioned rats. This potentiation could be attenuated by prazosin and yohimbine. It appears that in rats alpha-adrenoceptors in the peripheral vascular system are sensitized by DCLHb.