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Extra info for Advances in Nitrate Therapy
Although calcium antagonists may improve myocardial performance in some of these patients, it is not rational to use agents with a negative inotropic effect when agents with no such effect may be used. Moreover, nitrates are an established therapy for heart failure and in patients with combined angina pectoris, and heart failure monotherapy with nitrates is effective for both conditions. It should also be remembered that in some cases nifedipine has actually aggravated heart failure. At present there is one theoretical advantage for the use of beta-blockers in patients with postinfarction angina - the possibility of secondary prevention.
I believe that both effects playa role. Animal studies by Sheehan and coworkers  revealed, however, that nitroglycerin salvaged ischemic myocardium only in the presence of congestive heart failure. This suggests that the hemodynamic effects predominate. In most centers nitrates are not used at present for the indication of myocardial salvage. They are, however, frequently used to treat congestive heart failure in patients with acute myocardial infarction and probably contribute to limitation or even reduction of infarct size in this important subgroup.
Chronic exposure to nitroglycerin is directly related to down-regulation of the cGMP system. In animals which were made tolerant to nitroglycerin the activation of guanylate cyclase by the drug was reduced by about 75%, and the cGMP-phosphodiesterase activity was markedly increased . In view of the cGMP effect Kukovetz et al  have recently tried to find out whether tolerance is a peripheral phenomenon occurring in the vascular smooth muscle, and whether it is related to an impairment of guanylate cyclase activation.