Table 3

Comparative analysis of BBB permeability after NO prodrug infusion

NO ProdrugAverage [14C]Sucrose Clin Ipsilateral ForebrainAverage [14C]Sucrose ClinPredicted NO Congener Release in the CerebrovasculatureΔMAP at 60 min
% osmotic opening μM % change from baseline
Thionitrite (NO·, NO, NO+)
 Saline4.61  ± 0.540.000
 CD4.28  ± 0.600.000−2.17  ± 2.44
 SNAPcbv (0.191 μmol/min)5.18  ± 0.641.009.7−9.88  ± 5.28
 SNAP-CDfem(1.7 mmol/min)5.31  ± 0.241.200.016−31.6  ± 9.983-150
 SNAP-CDcbv (1.7 mmol/min)30.4  ± 1.473-151 44.2486−31.2  ± 1.113-150
Nitroxyl agents (NO·, NO)
 Angeli's Salt14.9  ± 0.65*** 17.6547−25.4  ± 10.83-150
 Piloty's Acid5.28  ± 0.671.15N.D.−1.15  ± 8.14
Diazeniumdiolates (NO·) (i.e. NONOates)
 Saline6.32  ± 0.760.0004.73  ± 10.4
 MAHMA NONOate11.0  ± 0.37** 8.27415−42.2  ± 11.8**
 Diethylamine NONOate11.2  ± 0.94** 8.62205−51.2  ± 4.52**
 Spermine NONOate8.88  ± 0.393-150 4.5212−53.9  ± 3.24**
 DETA NONOate6.39  ± 0.740.120.37−24.3  ± 15.3

Data are mean ± S.E. of three to six rats. The drug infusions were: each nitroxyl agent, 1.7 mmol/min; each NONOate agent, 1.7 mmol/min. Statistical significance was assessed by one-way ANOVA with Newman-Keuls post hoc test. Data with dissimilar (or no) superscripts are statistically different from other drug treatments and are statistically similar to values with the same superscript. The %osmotic opening (relative to mannitol) was calculated as (test drug Clin − mean control Clin)/(mean mannitol Clin− mean control Clin) · 100%.

  • cbv, cerebrovascular administration via the external carotid artery; fem, systemic administration via the femoral artery.

  • 3-150 P < .05; **P < .01; ***P < .005;

  • 3-151 P < .001.