Effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the potency of sodium nitroprusside and nitroglycerine to decrease blood pressure in rats: a dose-response study

Artif Cells Blood Substit Immobil Biotechnol. 2000 Sep;28(5):385-96. doi: 10.3109/10731190009118583.

Abstract

The nitrovasodilators, sodium nitroprusside and nitroglycerine, effect a dose-dependent decrease in mean arterial blood pressure (MABP) by liberating nitric oxide. Alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) is known to bind nitric oxide. We studied the effect of DCLHb on the potency of sodium nitroprusside (n=36) and nitroglycerine (n=36) to decrease MABP in rats which received 1, 10, 100, 1,000, or 10,000 mg/kg of the DCLHb, or normal saline as the Control. Six doses of sodium nitroprusside or nitroglycerine were given to each rat in a systematically varied sequence. For both drugs, in rats given 1, 10, or 100 mg/kg of DCLHb there were no between groups differences in the change in MABP compared to the Control group. For rats that received 1,000 or 10,000 mg/kg of DCLHb, the potency of nitroglycerine and sodium nitroprusside to decrease MABP was less (p<0.05) than the other groups. These data support the hypothesis that small doses of DCLHb effect a minimal change in the potency of nitrovasodilators to reduce blood pressure. However, they suggest that clinically relevant doses of DCLHb attenuate the vasodilatory ability of sodium nitroprusside and nitroglycerine.

MeSH terms

  • Animals
  • Aspirin / analogs & derivatives*
  • Aspirin / pharmacology*
  • Blood Pressure / drug effects
  • Blood Substitutes / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Hemoglobins / pharmacology*
  • Male
  • Nitroglycerin / pharmacology
  • Nitroprusside / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilator Agents*

Substances

  • Blood Substitutes
  • Hemoglobins
  • Vasodilator Agents
  • Nitroprusside
  • diaspirin-cross-linked hemoglobin
  • Nitroglycerin
  • Aspirin