The anti-angina efficacy of the continuous (C) transdermal application of nitroglycerin may lessen or disappear over the course of time. Pharmacological tolerance, which is probably responsible, might be prevented by intermittent (I) application. However few studies have compared the C and I methods. The effects of transdermal patches containing 10 mg, applied for 24 hours/day and for 15 hours/day for one week were evaluated in twelve patients. Exercise tests were performed before and 4 hours after the initial application and after one week of each type of treatment prescribed in random order with a 7 day wash-out between each treatment phase. Plasma nitroglycerin concentrations were measured at the same time. Total work and ischemia and angina thresholds after 4 hours application all increased significantly in comparison with baseline values. All these values persisted after one week of I treatment. With C treatment they decreased though remained significantly above baseline values with the exception of angina thresholds. I treatment appeared significantly better than C treatment regarding ischemia threshold (3,974.7 kpm v. 3,037.5-p < 0.01). Plasma nitroglycerin levels were the same during each treatment phase. These results suggest that the anti-ischemic efficacy of transdermal patches persists after one week of treatment, though with superiority of intermittent treatment. Continuous treatment tends to induce pharmacodynamic tolerance since there was no difference in plasma nitroglycerin levels.
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Redox Biol
January 2025
Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA; Lawrence D. Longo, MD Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address:
Repeated use of nitroglycerin results in a loss of its vasodilatory efficacy which limits its clinical use for the treatment of angina pectoris. This tolerance phenomenon is a defining characteristic of all compounds classified as nitrodilators, which includes NTG as well as S-nitrosothiols and dinitrosyl iron complexes. These compounds vasodilate via activation of soluble guanylate cyclase, although they do not release requisite amounts of free nitric oxide (NO) and some do not even cross the plasma membrane.
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Cardiovascular Department, Huntington Medical Research Institutes, Pasadena, CA, USA.
Sodium serves as one of the primary cations in the central nervous system, playing a crucial role in maintaining normal brain function. In this study, we investigated alterations in sodium concentrations in the brain and/or cerebrospinal fluid across multiple models, including an aging model, a stroke model, a nitroglycerin (NTG)-induced rat migraine model, a familial hemiplegic migraine type 2 (FHM2) mouse model, and a transgenic mouse model of Alzheimer's disease (AD). Our results reveal that older rats exhibited higher sodium concentrations in cerebrospinal fluid (CSF), plasma, and various brain regions compared to their younger counterparts.
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IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
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