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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1986-09, Vol.334 (1), p.100-104
• Main Authors: BASSENGE, E, STREIN, K
• Format: Article
• Language: English
• Subjects: Animals; Antianginal agents. Coronary vasodilator agents; Arteries - drug effects; Biological and medical sciences; Blood Pressure - drug effects; Cardiac Output - drug effects; Cardiovascular system; Coronary Circulation - drug effects; Dogs; Dose-Response Relationship, Drug; Female; Heart Rate - drug effects; Hemodynamics - drug effects; Isosorbide Dinitrate - analogs & derivatives; Isosorbide Dinitrate - pharmacology; Male; Medical sciences; Pharmacology. Drug treatments; Vascular Resistance - drug effects; Veins - drug effects
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00498746

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 less than or equal to 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.