1987
DOI: 10.1161/01.cir.76.3.572
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Nitrate tolerance: the lack of effect of N-acetylcysteine.

Abstract: The hemodynamic and antianginal effects of 30 mg of isosorbide dinitrate (ISDN) were assessed in 12 patients with chronic stable angina after initial dosing and after 7 to 10 days of therapy four times daily. During early therapy, ISDN produced significant hemodynamic and antianginal effects that persisted over a 3 hr observation period. During sustained therapy there was attenuation of the hemodynamic effects at rest, and treadmill exercise time to the onset of angina and to the development of moderate angin… Show more

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Cited by 89 publications
(18 citation statements)
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“…In several reports, administration of N-acetylcysteine may reverse nitrovasodilator resistance (38)(39)(40)(41)(42). However, other studies failed to demonstrate benefit of sulfhydryl repletion (44)(45)(46), and when tissue thiol levels have been evaluated directly, no deficiency was observed (47). The clinically beneficial effect of thiol administration may represent a compensation, not a correction, of the underlying defect.…”
Section: Discussionmentioning
confidence: 99%
“…In several reports, administration of N-acetylcysteine may reverse nitrovasodilator resistance (38)(39)(40)(41)(42). However, other studies failed to demonstrate benefit of sulfhydryl repletion (44)(45)(46), and when tissue thiol levels have been evaluated directly, no deficiency was observed (47). The clinically beneficial effect of thiol administration may represent a compensation, not a correction, of the underlying defect.…”
Section: Discussionmentioning
confidence: 99%
“…Chronic administration of nitrates may well deplete intracellular stores of reduced SH groups and cause tolerance. Reversal of nitrate tolerance by the addition of SH group replenishing agents has been demonstrated in vitro (Needleman & Johnson, 1973) but in vivo studies have been contradictory (Packer et al, 1987;Parker et al, 1987b). These latter studies both involved patients with either congestive heart failure (Packer et al, 1987) or chronic angina (Parker et al, 1987) and both administered NAC as a single large dose after tolerance had been established.…”
Section: Plasma Gtn Concentrationmentioning
confidence: 99%
“…While this has been shown in vitro (Needleman & Johnson, 1973) in vivo human studies have been contradictory (Packer et al, 1987;Parker et al, 1987b).…”
Section: Introductionmentioning
confidence: 99%
“…21 22 Observations in human subjects have shown reversal of attenuation of hemodynamic and coronary effects of NTG by administration of Nacetylcysteine, or enhanced nitrate responsiveness during coadministration ofN-acetylcysteine.23-25How-ever, reversal of antianginal attenuation by N-acetylcysteine has not been demonstrated. 26 In addition, attenuation of antianginal effect may be related, at least in part, to counterregulatory hormonal and neural mechanisms, offsetting the direct vascular effects of NTG. The weight gain observed in our patients on the active NTG infusion day suggests that fluid retention does occur during long-term NTG infusion, and could result in a gradual increase in left ventricular volume over 24 hr.…”
mentioning
confidence: 99%