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PubMed · 6430767

Nitrate tolerance.

J O Parker
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Abstract

These studies have shown the following: Tolerance to the hemodynamic and antianginal effects of isosorbide dinitrate. Tolerance develops quickly and can be demonstrated within 24 hours. Tolerance is rapidly reversed and the return of normal responsiveness is seen within 21 hours withdrawal of isosorbide dinitrate. Cross-tolerance occurs between the hemodynamic effects of isosorbide dinitrate and nitroglycerin. When tolerance is present, the next dose of isosorbide dinitrate does exert an effect, although somewhat less in magnitude and duration. Sublingual isosorbide dinitrate and nitroglycerin restores exercise performance despite tolerance to oral isosorbide dinitrate.

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Angina PectorisClinical Trials as TopicDose-Response Relationship, DrugDouble-Blind MethodDrug ToleranceExercise TestHemodynamicsHumansIsosorbide DinitrateLong-Term CareMaleNitroglycerinClinical TrialJournal Article

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J O Parker. 1984. Nitrate tolerance.. https://pubmed.ncbi.nlm.nih.gov/6430767/

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Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.

OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. METHODS: Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.

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