Reduced nitric oxide reactivity of a new recombinant human hemoglobin attenuates gastric dysmotility.
The objective of this investigation was to compare the gastric motility effects of two recombinant hemoglobin variants, rHb1.1, and rHb3011, the latter having decreased nitric oxide reactivity via mutagenic alteration. Variants were administered to rats at 750 and 1500 mg/kg, i.v., prior to feeding a meal. The percentage of meal emptied was determined 45 min after feeding. rHb1.1 reduced gastric emptying significantly (48% and 71%), whereas rHb3011 was significant (42%) only at the higher dose (p < 0.05). The results suggest that rHb1.1 inhibits gastric emptying by scavenging NO, and this effect is significantly reduced by rHb3011, which has decreased NO reactivity.
Hartman
J C
JC
Baxter Hemoglobin Therapeutics, Boulder, CO 80301, USA. hartmac@baxter.com
Argoudelis
G
G
Doherty
D
D
Lemon
D
D
Gorczynski
R
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D011994:Recombinant Proteins; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester