Dose responses of vasodilators after steady-state hemoglobin
versus
L-NAME infusions. (A) Experimental timeline. Rats were stabilized for 30 min after surgery, and blood gases were drawn as indicated (BG1 and BG2). Subsequently, purified human hemoglobin (8.1 mM) was infused until an end concentration of 175 mg/kg was reached. After steady-state vasoconstriction, a dose response with vasodilator was performed. Rats were followed for approximately 45 mins after hemoglobin infusion. Effect of dose response of (B). SNP (0.4, 1.2, 4, and 12 μg/kg/min, n=6) or (C). sildenafil (10, 30, 100 and 300 μg/kg/min, n=5) and (D). bolus administration of BAY 41-8543 (10, 30, 100, and 300 μg/kg, n=5) and (E). BAY 60-2770 (1, 3, 10, and 30 μg/kg, n=5) on steady-state MAP after human hemoglobin (175 mg/kg) infusions (- ● -closed dots) compared with effects of the same vasodilator infusions after steady-state L-NAME (1 mg/kg) infusion (- ◯ -open dots). Asterisks indicate significant difference from hemoglobin at same dose (*p<0.05, **p<0.01, ***p<0.001) by two-way ANOVA with Bonferroni correction.