Decrease in plasma NOx concentration by isosorbide dinitrate, an organic nitrate ester.
It has been suggested that isosorbide dinitrate (ISDN)-induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential increase in plasma concentrations of NOx (NO2- and NO3-, stable end-products of NO) in venous blood than arterial blood. Plasma NOx was measured by high-performance liquid chromatography-Griess system with a sensitivity of 0.01 microM for NO2- and 0.1 microM for NO3-. Arterial and venous blood samples were obtained after coronary angiography from the aorta and right atrium of patients with or without ischemic heart disease. Nicardipine, a calcium channel blocker, was used as a non-NO-related arteriovasodilator. At 1 mg i.v., it did not cause any changes in NOx concentration in arterial and venous blood irrespective of hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2- and decreased NO3- in both arterial and venous blood, with concomitant venodilation. Further analysis revealed that plasma NO increased in the pulmonary circulation and this increase was preserved after nicardipine and ISDN, and that ISDN, but not nicardipine, increased plasma NO3- in the pulmonary circulation. The authors did not detect higher concentrations of NOx in venous blood relative to their level in arterial blood. Further studies are necessary to clarify the kinetics of NO and NO-related compounds in the whole body.
Ishibashi
Takaharu
T
Department of Pharmacology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. ishitaka@kanazawa-med.ac.jp
Himeno
Mariko
M
Kubota
Kaname
K
Matsubara
Taku
T
Hori
Tomoyuki
T
Ozaki
Kazuyuki
K
Yamazoe
Masaru
M
Aizawa
Yoshifusa
Y
Yoshida
Junko
J
Nishio
Matomo
M
D000368:Aged; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D009529:Nicardipine; D007548:Isosorbide Dinitrate