SYSTEMIC AND CORONARY VASCULAR EFFECTS OF THE 2- AND THE 5-MONONITRATE ESTERS OF ISOSORBIDE

The systemic and coronary vascular effects of the 2- and 5-mononitrate metabolites of isosorbide dinitrate (ISDN) were compared to those produced by ISDN and nitroglycerin (GTN) after i.v. and i.a. administration in dogs. The hemodynamic effects of the two isosorbide (IS) mononitrates were generally qualitatively similar to those observed after ISDN and GTN. Intravenous administration of the organic nitrates decreased systolic and diastolic blood pressure and tended to narrow pulse pressure. GTN, ISDN and the 2-IS mononitrate metabolite produced initial transient increases in cardiac output, coronary blood flow and heart rate, followed by gradual decreases to below control levels. Initial increases in cardiac output and coronary blood flow were not observed after i.v. infusion of the 5-IS mononitrate. Calculated systemic and coronary vascular resistance decreased, then gradually increased, in some instances to above control, after i.v. infusion of all four organic nitrates. The order of vasodilator potency in both the systemic and coronary vascular beds was GTN, ISDN, 2-IS mononitrate and 5-IS mononitrate, the latter agent being the least potent. No significant differences in duration of vascular response were observed between these compounds. The pharmacologic findings are discussed in light of current concepts regarding relationships between vasodilator activity and biotransformation of the organic nitrates.