NOREPINEPHRINE RELEASE DURING VASOCONSTRICTION INDUCED BY CROSS-LINKED HEMOGLOBIN

The presser 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 des igned to determine if contraction occurring in response to alpha alpha -cross-linked hemoglobin (XL-Hb) is due in part to increased exit of N E from vascular nerve endings. Helical strips of canine femoral artery were superfused in vitro with Krebs-Ringer solution and, for each str ip, the overflow of NE into the superfusate as well as contractile res ponses were measured concurrently during basal conditions, during nerv e stimulation and during tyramine-evoked release of NE. XL-Hb (10 mu M ) contracted unstimulated strips without affecting NE overflow. NE ove rflow also was unchanged by NG-monomethyl-L-arginine (L-NMMA; 300 mu M ), an inhibitor of NO synthesis; by sodium nitroprusside (SNP; 1 mu M) an NO donor; by a combination of XL-Hb and L-NMMA; or of XL-Hb and SN P. These treatments contracted the strips to the same degree as did XL -Hb alone, except for SNP, which induced relaxation. Transmural stimul ation of the strips at 2 and 10 Hz induced NE overflow and contraction , neither of which was affected by any treatment except SNP which sign ificantly (P < 0.05) increased NE overflow while inhibiting contractio n. In other experiments, XL-Hb augmented contractions induced by tyram ine (10 mu M) although the resulting NE release was unaffected. These results suggest that, in the femoral artery, contractions induced by X L-Hb are not due to increased efflux of NE from vascular nerve endings but are consistent with inhibition of the the actions of NO.