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Counterregulatory responses: sustained-release isosorbide-5-mononitrate versus transdermal nitroglycerin
1Department of Medicine, University of Toronto, Mount Sinai Hospital, Ontario, Canada.
Journal of Cardiovascular Pharmacology
|November 1, 1996
Summary
Sustained-release isosorbide-5-mononitrate and transdermal nitroglycerin both cause similar counterregulatory responses, including plasma volume expansion. Neurohormonal activation is minimal with these nitrate therapies.
Area of Science:
- Cardiovascular Pharmacology
- Pharmacodynamics
- Clinical Investigation
Background:
- Nitroglycerin therapy is known to induce counterregulatory physiological responses.
- Understanding these responses is crucial for optimizing nitrate-based cardiovascular treatments.
Purpose of the Study:
- To document counterregulatory responses to sustained-release isosorbide-5-mononitrate (ISMN).
- To contrast ISMN responses with those of continuous transdermal nitroglycerin (NTG).
Main Methods:
- A 5-day, single-blind, parallel study in 20 male volunteers.
- Comparison of ISMN versus transdermal NTG.
- Assessment of blood pressure, heart rate, hematocrit, catecholamines, and renin activity.
Main Results:
- Both ISMN and NTG decreased systolic blood pressure and increased heart rate.
- Blood pressure effects diminished within 48 hours; heart rate effects persisted and were greater with ISMN.
- Hematocrit decreased, indicating sustained plasma volume expansion, with slow resolution after NTG removal.
- Minimal changes in plasma catecholamines and modest changes in plasma renin activity were observed.
Conclusions:
- Counterregulatory responses to ISMN are comparable to continuous transdermal NTG.
- Plasma volume expansion is a sustained effect of repeated nitrate dosing.
- Neurohormonal activation during nitrate therapy is modest.