Evaluation of pharmacological modulation of nitroglycerin-induced impairment of nitric oxide bioavailability by a catheter-type nitric oxide sensor

Circ J. 2007 Sep;71(9):1473-9. doi: 10.1253/circj.71.1473.

Abstract

Background: The present study aimed to elucidate the effect of long-term treatment with nitroglycerin (NTG) on the bioavailability of nitric oxide (NO) examined by a catheter-type NO sensor. The study also examined whether these effects could be modified by an antioxidant, an angiotensin converting enzyme inhibitor, or an angiotensin II type 1 receptor antagonist (ARB).

Methods and results: Male New Zealand rabbits were treated for 7 days with NTG patches, either alone or in combination with tempol, enalapril, or valsartan (ARB). The plasma NO concentration was measured with the catheter-type NO sensor. The plasma peroxynitrite concentration was measured by enzyme-linked immunosorbent assay. An increase in plasma NO concentration in response to acetylcholine (ACh) were significantly attenuated in the NTG-treated group as compared with the control. Plasma peroxynitrite concentration in NTG-treated group was significantly higher as compared with the control. The negative effects of NTG were significantly suppressed by the co-treatment with tempol, enalapril or valsartan.

Conclusions: Chronic treatment of rabbits with NTG elicits the impairment of the ACh-stimulated NO production. In addition, the negative effects of NTG might be prevented by the co-treatment with drugs attenuating nitrosative stress.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Catheterization*
  • Drug Monitoring* / instrumentation
  • Drug Monitoring* / methods
  • Male
  • Nitric Oxide / blood*
  • Nitroglycerin / pharmacology*
  • Peroxynitrous Acid / blood*
  • Rabbits
  • Vasodilator Agents / pharmacology*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Vasodilator Agents
  • Peroxynitrous Acid
  • Nitric Oxide
  • Nitroglycerin