Mechanism of the acute pressor effect and bradycardia elicited by diaspirin crosslinked hemoglobin in anesthetized rats

Abstract

Diaspirin crosslinked hemoglobin (DCLHb) is a chemically stabilizedhemoglobin (Hb) that induces an increase in blood pressure and a decrease of heart rate wheninjected intravenously in some animals. The mechanism by which DCLHb elicits thesehemodynamic effects was studied in pentobarbital-anesthetized, vagotomized rats using a varietyof drugs known for their inhibitory action towards endogenous hemodynamically active systems.The hypertensive episode elicited by DCLHb (100 or 400 mg·kg–1) was attenuatedin animals pretreated with NG-nitro-L-arginine (inhibitor of nitric oxidesynthases) throughout the 30-min period of observation, but it was not reduced in thosepretreated 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 withcontrol animals. With the exception of propranolol and BIBP-3226, none of the aforenamedinhibitors 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 inour animal model requires the presence of an endogenous nitric oxide generating system to beexpressed; (ii) the bradycardia elicited by DCLHb might involve the participation ofneuropeptide Y and (or) its NPY-1 receptors, but it is unlikely to involve abaroreceptor-mediated vagal reflex, at least in our animal model.Key words: hemoglobin, nitric oxide, blood pressure, heart rate,DCLHb.