Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric and human radial collateral arteries.
The actions of the blood substitute diaspirin crosslinked hemoglobin (DCLHb) were investigated in rat (small mesenteric artery) and human (radial collateral artery) resistance vessels mounted in a wire myograph for isometric tension recording. DCLHb did not contract resting vessels from rats, but vasoconstrictor responses were observed in isolated arteries and perfused mesenteric beds prestimulated with threshold concentrations of methoxamine. The DCLHb contractile responses were greatly attenuated by N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or endothelial removal, whereas BQ-123 (endothelin A receptor antagonist), prazosin (alpha1-adrenoceptor antagonist), or indomethacin (cyclooxygenase inhibitor) had no effect. Endothelium-dependent relaxations to carbachol in both rat mesenteric and human radial collateral artery were inhibited by DCLHb. Relaxations to carbachol were studied in the presence of L-NAME or 25 mM KCl to investigate the effect of DCLHb on endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide, respectively. In both rat and human vessels, EDHF-mediated relaxations were not affected by DCLHb preincubation, whereas the nitric oxide component of carbachol-induced relaxations was practically abolished. In conclusion, inhibition of the effects of basal nitric oxide release underpins the vasoconstrictor effects of DCLHb. DCLHb effectively abolishes the nitric oxide component of carbachol-induced relaxation, with no effect on the EDHF-mediated component in both isolated rat mesenteric and human radial collateral arteries.
Vuylsteke
A
A
Department of Anaesthesia, Papworth Hospital, Cambridge, UK.
Davidson
H J
HJ
Ho
W S
WS
Ritchie
A J
AJ
Callingham
B A
BA
White
R
R
Hiley
C R
CR
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001802:Blood Substitutes / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D001802:Blood Substitutes; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D010456:Peptides, Cyclic; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D003994:Bucladesine; D002217:Carbachol; C083478:diaspirin-cross-linked hemoglobin; D008729:Methoxamine; D001241:Aspirin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin