Isosorbide dinitrate blocks thromboxane synthesis caused by CO2 in dog heart-lung preparation

Effects of isosorbide dinitrate (ISDN) on coronary flow and arterial prostaglandin (PG) concentrations were investigated, using dog heart-lung preparations. Two kinds of gases (low and high CO2 gases) were used for the artificial respiration. Low CO2 gas contained 55% O2 and 0.2% CO2, whereas high CO2 gas contained 55% O2 and 8% CO2. Administration of ISDN into a blood reservoir at high CO2 caused an increase in coronary sinus blood flow, which was blocked by indomethacin, but not at low CO2. In the absence of ISDN, the arterial concentration of thromboxane (TX) B2 was larger at high CO2 than at low CO2. ISDN attenuated such an increase in TXB2 concentration caused by CO2. The arterial concentration of 6-keto PGF1 alpha was altered by neither CO2 nor ISDN, but slightly increased with time. Indomethacin lowered the concentrations of 6-keto PGF1 alpha and TXB2. These results suggested that the arterial CO2 tension enhanced the TXA2 synthesis and that ISDN inhibited such a relation between CO2 and TXA2 synthesis. Additionally, the vasodilatory effects of PGI2 was enhanced by elevating the arterial CO2 tension. Thus, the increase in canine coronary flow at high CO2 in the presence of ISDN may be related to the inhibitory effects of ISDN on the TXA2 synthesis enhanced by the high arterial CO2 tension and the facilitatory effects of CO2 on the PGI2-induced vasodilation.