The effects of nitric oxide synthase – versus lipoxygenase inhibition on coronary flow and nitrite outflow in isolated rat heart

Rok, strany: 2005, 199 - 207

The aim of this study was to assess the changes of coronary flow (CF) and nitrite outflow under inhibition of nitric oxide synthase (NOS) by N^ω-nitro-L-arginine monomethyl ester (L-NAME) or lipoxygenase (LOX) induced by nordihydroguaiaretic acid (NDGA) in isolated rat heart. The hearts of male Wistar albino rats (n = 18, age 8 weeks, body mass 180–200 g) were retrograde perfused according to the Langendorff’s technique at gradually increased constant coronary perfusion pressure (CPP) conditions (40–120 cm H2O) which induced flow-dependent nitric oxide (NO) release (nitrite outflow). The experiments were performed during control conditions, in the presence of NO synthesis inhibitor L-NAME (30 µmol/l) or nonspecific LOX inhibitor (NDGA, 0.1 mmol/l) which were administered separately or in combination. CF varied in autoregulatory range from 4.12 ± 0.26 ml/min/g wt at 50 cm H2O to 5.22 ± 0.26 ml/min/g wt at 90 cm H2O. In autoregulatory range, nitrite outflow varied from 2.05 ± 0.17 nmol/min/g wt at 50 cm H2O to 2.52 ± 0.21 nmol/min/g wt at 90 cm H2O and was strictly parallel with CPP/CF curve. The autoregulatory range of CF was significantly extended (40–100 cm H2O, 2.22 ± 0.12 ml/min/g wt and 2.90 ± 0.25 ml/min/g wt, respectively) under the influence of L-NAME. Hemodynamic effects were accompanied by significant decrease in nitrite outflow after L-NAME administration (0.56 ± 0.11 nmol/min/g wt at 40 cm H2O to 1.45 ± 0.14 nmol/min/g wt at 100 cm H2O). NDGA affected CF in the range of CPP 40–70 cm H2O only (from 42 % at 50 cm H2O to 12 % at 90 cm H2O, respectively) with no significant changes in nitrite outflow. When L-NAME was applied in combination with NDGA vs. NDGA only, CF was significantly reduced (from 34 % at 50 cm H2O to 50 % at 90 cm H2O, respectively) with parallel changes in nitrite outflow (from 40 % at 50 cm H2O to 51 % at 90 cm H2O, respectively). The results showed that CF and nitrite outflow could be decreased under L-NAME administration. Nonselective LOX inhibitor (NDGA) decreased control values of CF only at lower values of CPP but did not change nitrite outflow indicating antioxidant properties of NDGA. In addition, L-NAME decreased the effects induced by NDGA on CF and nitrite outflow indicating the role of NO.

ISO 690:

Jakovljevic, V., Djuric, D. 2005. The effects of nitric oxide synthase – versus lipoxygenase inhibition on coronary flow and nitrite outflow in isolated rat heart. In General Physiology and Biophysics, vol. 24, no.2, pp. 199-207. 0231-5882.

APA:

Jakovljevic, V., Djuric, D. (2005). The effects of nitric oxide synthase – versus lipoxygenase inhibition on coronary flow and nitrite outflow in isolated rat heart. General Physiology and Biophysics, 24(2), 199-207. 0231-5882.