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Diaspirin cross-linked hemoglobin (DCLHB): involvement of adrenergic mechanisms in the pressor effect
1Department of Pharmacodynamics (m/c 865), University of Illinois at Chicago 60612-7231.
Insights
Diaspirin cross-linked Hemoglobin (DCLHb) enhances blood pressure by acting on the peripheral vasculature, not the central nervous system or adrenal medulla. It also potentiates pressor responses to other agents like norepinephrine and phenylephrine.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Resuscitative Solutions
Background:
- Diaspirin cross-linked Hemoglobin (DCLHb) is a resuscitative solution known to cause a pressor effect.
- The precise mechanisms underlying DCLHb's pressor effect, particularly the involvement of the central nervous system (CNS) and adrenal medulla, require elucidation.
Purpose of the Study:
- To investigate the role of the central nervous system (CNS) in the pressor effect of DCLHb.
- To determine if the adrenal medulla mediates the pressor response to DCLHb.
- To examine the influence of DCLHb pretreatment on the pressor effects of various vasoactive agents.
Main Methods:
- Administration of DCLHb to rats with cervical sectioning to isolate the peripheral effects.
- Administration of DCLHb to bilaterally adrenal demedullated rats.
- Assessment of DCLHb's potentiation of norepinephrine, phenylephrine, and clonidine-induced blood pressure changes.
- Use of alpha-adrenergic antagonists (phenoxybenzamine, prazosin, yohimbine) to confirm specificity.
Main Results:
- DCLHb produced a comparable pressor effect in both normal and cervical sectioned rats, indicating peripheral mediation.
- DCLHb induced a similar pressor effect in normal and adrenal demedullated rats, ruling out adrenal medulla involvement.
- DCLHb significantly potentiated the pressor responses to norepinephrine, phenylephrine, and clonidine, even in cervical sectioned rats.
- The potentiation of clonidine's pressor effect was attenuated by alpha-adrenergic antagonists, confirming its vascular mechanism.
Conclusions:
- The pressor effect of DCLHb is primarily mediated by the peripheral vascular system, independent of the central nervous system.
- The adrenal medulla does not play a significant role in the pressor response to DCLHb.
- DCLHb enhances vascular sensitivity to endogenous and exogenous catecholamines and other pressor agents.
Abstract:
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)