Dose-dependent effects of isosorbide-5-mononitrate on the venous arterial and coronary arterial system of conscious dogs

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Abstract
Isosorbide-5-mononitrate (IS-5-MN), the main metabolite of isosorbide dinitrate shows antianginal efficacy and is being used increasingly as a drug for practical therapy. In conscious dogs we therefore measured the effects of increasing doses of IS-5-MN on hemodynamic parameters and the diameter of the circumflex artery. We found a dose dependent reduction of the mean right atrial pressure, the systolic blood pressure and a dilatation of the circumflex artery. For all three parameters threshold dosages were between 0.01 and 0.03 mg/kg. On the contrary peripheral and coronary resistance did not change at doses ≤0.3 mg/kg. The heart rate was significantly increased only at doses above 1 mg/kg and the diastolic blood pressure also showed a tendency to fall only at doses above 1 mg/kg. Cardiac output and coronary flow were not significantly altered over the entire dose range investigated, with the exception of a transient rise in coronary blood flow after the injection of 2.5 mg/kg IS-5-MN. From our results we can deduce that in the low dose range reduction of preload and dilatation of large arteries are the main effects of IS-5-MN. In contrast, no reduction of the coronary or peripheral resistance is to be expected.