Mechanisms of tolerance during treatment with nitroglycerin patches for 24 h.
OBJECTIVE
We examined the relationship between tolerance development, counterregulatory responses and arterial vasodilating effects evaluated by digital pulse plethysmography.


METHODS
Twenty patients with stable angina pectoris were exercise tested before, after 2 and after 24 h of open nitrate patch treatment.


RESULTS
The effects observed after 2 h of treatment on exercise duration, ST-segment depression, blood pressure and heart rate were lost in most individuals after 24 h. In contrast, the effects on the arterial pulse curves persisted after 24 h, with a mean change from baseline of 29%, compared to 33% at 2 h. After 24 h, a significant decrease in haematocrit and an increase in body weight were observed. The haematocrit changes correlated with the loss of clinical efficacy (r = 0.57 for ST-segment depression, and r = 0.54 for exercise duration).


CONCLUSIONS
Clinical nitrate tolerance may be observed despite maintenance of the arterial vasodilating effects, and tolerance is more related to plasma volume expansion as a counterregulatory mechanism.
Klemsdal
T O
TO
Department of Cardiology, Ullevål University Hospital, Oslo, Norway.
Mundal
H H
HH
Gjesdal
K
K
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D004361:Drug Tolerance; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D005996:Nitroglycerin