Mechanism of the acute pressor effect and bradycardia elicited by diaspirin crosslinked hemoglobin in anesthetized rats.
Diaspirin crosslinked hemoglobin (DCLHb) is a chemically stabilized hemoglobin (Hb) that induces an increase in blood pressure and a decrease of heart rate when injected intravenously in some animals. The mechanism by which DCLHb elicits these hemodynamic effects was studied in pentobarbital-anesthetized, vagotomized rats using a variety of drugs known for their inhibitory action towards endogenous hemodynamically active systems. The hypertensive episode elicited by DCLHb (100 or 400 mg.kg-1) was attenuated in animals pretreated with NG-nitro-L-arginine (inhibitor of nitric oxide synthases) throughout the 30-min period of observation, but it was not reduced in those pretreated with a variety of sympatholytic drugs (e.g., prazosin), atropine, BIBP-3226 (neuropeptide Y antagonist), indomethacin, [1-(beta-mercapto-beta,beta-cyclopentanemethylene propionic acid), 2-(0-methyl) tyrosine]-Arg8 vasopressin (vasopressin antagonist), losartan (angiotensin antagonist), bosentan (endothelin antagonist), or L-arginine-(nitric oxide precursor), compared with control animals. With the exception of propranolol and BIBP-3226, none of the aforenamed inhibitors reduced the amplitude of the bradycardia associated with the pressor effect of DCLHb. These results suggest that: (i) the acute (< 30 min) pressor activity of DCLHb in our animal model requires the presence of an endogenous nitric oxide generating system to be expressed; (ii) the bradycardia elicited by DCLHb might involve the participation of neuropeptide Y and (or) its NPY-1 receptors, but it is unlikely to involve a baroreceptor-mediated vagal reflex, at least in our animal model.
Moisan
S
S
Centre de Recherche (Université Laval), Hôtel-Dieu de Québec, Canada.
Drapeau
G
G
Burhop
K E
KE
Rioux
F
F
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000494:pharmacology*; D001919:Bradycardia / Q000139:chemically induced*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D014628:Vagotomy
C092926:BIBP 3226; D001802:Blood Substitutes; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester