[Dose-response behavior and long-term effect of organic nitrates. Experimental and clinical studies]

The effect of isosorbide dinitrate (ISDN) in patients with stable angina pectoris consists of an effect on the capacity vessels, of an increase in the arterial compliance (wind kessel function), a dilation of reactive stenoses in the coronary system, an improvement in the collateral function and a direct myocardial effect. In practice isosorbide dinitrate should be given preferably in single doses of 20 mg or more in a non-depot form for maintenance therapy; oral administration three or four times a day is appropriate. The dose effect relation justifies a dose increase in individual cases. Taking the galenics and therapy intervals into consideration, an anti-anginal effect can be seen in acute as well as chronic treatment. With chronic administration of the substance a weakening of the haemodynamic effects occurs. This does not necessarily interfere with the anti-ischemic effect. This weakening can best be explained by counter-regulatory processes. With the usual nitrate doses a tolerance on the vasculary level is not reached, i.e. an alteration in molecular processes. On the other hand, under conditions, under which the weakening of haemodynamic effects becomes fully visible, as for example in ergometric exercise with elevated legs, a decrease in the antianginal efficacy can be observed during a maintenance therapy with isosorbide dinitrate.