Decrease in plasma NOx concentration by isosorbide dinitrate, an organic nitrate ester.

Area of Science:

• Cardiovascular Pharmacology
• Nitric Oxide Biology

Background:

• Isosorbide dinitrate (ISDN) is known to induce venodilation.
• This effect is hypothesized to be due to preferential accumulation in venous tissues, leading to increased nitric oxide (NO) concentrations.

Purpose of the Study:

• To investigate if ISDN-induced venodilation correlates with a preferential increase in plasma nitric oxide metabolites (NOx) in venous blood compared to arterial blood.
• To compare the effects of ISDN with nicardipine, a non-NO-related vasodilator, on plasma NOx levels.

Main Methods:

• Plasma NOx (nitrite and nitrate) concentrations were measured using high-performance liquid chromatography-Griess system.
• Arterial and venous blood samples were collected from patients undergoing coronary angiography.
• ISDN and nicardipine were administered intravenously, and hemodynamic changes were monitored.

Main Results:

• ISDN administration increased nitrite and decreased nitrate in both arterial and venous blood, accompanied by venodilation.
• Nicardipine did not alter NOx concentrations in either blood type.
• Plasma NO levels increased in the pulmonary circulation after ISDN, an effect not observed with nicardipine.
• No preferential increase in NOx concentrations was detected in venous blood relative to arterial blood.

Conclusions:

• The venodilating effect of ISDN is not associated with higher NOx concentrations in venous blood compared to arterial blood.
• ISDN influences NO and NOx metabolism in the pulmonary circulation.
• Further research is required to fully elucidate the systemic kinetics of NO and its metabolites.