Norepinephrine release during vasoconstriction induced by cross-linked hemoglobin.
The pressor effect of hemoglobin-based blood substitutes is due partly to their capacity to scavenge nitric oxide (NO), a potent vasodilator. NO also appears to modulate the release of norepinephrine (NE) from sympathetic nerve endings in some blood vessels. Thus studies were designed to determine if contraction occurring in response to alpha alpha-cross-linked hemoglobin (XL-Hb) is due in part to increased exit of NE from vascular nerve endings. Helical strips of canine femoral artery were superfused in vitro with Krebs-Ringer solution and, for each strip, the overflow of NE into the superfusate as well as contractile responses were measured concurrently during basal conditions, during nerve stimulation and during tyramine-evoked release of NE. XL-Hb (10 microM) contracted unstimulated strips without affecting NE overflow. NE overflow also was unchanged by NG-monomethyl-L-arginine (L-NMMA; 300 microM), an inhibitor of NO synthesis; by sodium nitroprusside (SNP; 1 microM) an NO donor; by a combination of XL-Hb and L-NMMA; or of XL-Hb and SNP. These treatments contracted the strips to the same degree as did XL-Hb alone, except for SNP, which induced relaxation. Transmural stimulation of the strips at 2 and 10 Hz induced NE overflow and contraction, neither of which was affected by any treatment except SNP which significantly (P < 0.05) increased NE overflow while inhibiting contraction. In other experiments, XL-Hb augmented contractions induced by tyramine (10 microM) although the resulting NE release was unaffected. These results suggest that, in the femoral artery, contractions induced by XL-Hb are not due to increased efflux of NE from vascular nerve endings but are consistent with inhibition of the the actions of NO.
Hunter
L W
LW
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Tyce
G M
GM
Rorie
D K
DK
D000818:Animals; D004285:Dogs; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D006454:Hemoglobins; D009638:Norepinephrine; D014439:Tyramine