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Updated: Jun 13, 2026
07:19
Preparation of Rat Skeletal Muscle Homogenates for Nitrate and Nitrite Measurements
Published on: July 29, 2021
Differences between nitrates: role of isosorbide 2-mononitrate.
Riccardo Raddino1, Giorgio Caretta, Ivano Bonadei
1Dipartimento di Medicina sperimentale Applicata, Sezione di malattie cardiovascolari, Università degli studi di Brescia, Brescia, Italy. Riccardo.raddino@libero.it
Journal of Cardiovascular Medicine (Hagerstown, Md.)
|April 24, 2010
Summary
2-mononitrate (2MN) exhibits reduced tolerance development compared to other nitrates like nitroglycerine (NTG). This suggests 2MN may offer a more sustained therapeutic effect for cardiovascular conditions by involving additional mechanisms beyond guanylate cyclase stimulation.
Area of Science:
- Cardiovascular Pharmacology
- Nitrate Vasodilators
- Drug Tolerance Mechanisms
Background:
- Nitrates are crucial in treating coronary heart disease and heart failure.
- A significant limitation of nitrate therapy is the rapid development of tolerance.
- Understanding nitrate tolerance is key to optimizing cardiovascular treatments.
Purpose of the Study:
- To compare the vasodilator effects of different nitrates on isolated rabbit cardiovascular tissues.
- To investigate the mechanisms underlying nitrate tolerance.
- To evaluate nitroglycerine (NTG), isosorbide dinitrate (ISDN), 5-mononitrate (5MN), and 2-mononitrate (2MN).
Main Methods:
- Isolated rabbit hearts and aortic strips were used.
- Spasmogenic agents (KCl, angiotensin II, noradrenaline) induced contractions.
- Nitrates were administered to assess inhibitory effects and tolerance induction via preincubation.
Main Results:
- Nitrates demonstrated varying inhibition of noradrenaline-induced contractions: NTG (90%), 2MN (80%), ISDN (60%), and 5MN (55%).
- Following preincubation, vasodilator effect loss was 50-60% for most nitrates, but significantly lower (36%) for 2MN.
- 2MN resulted in lower cyclic guanosine monophosphate (cGMP) levels compared to other nitrates.
Conclusions:
- 2-mononitrate (2MN) induces less tolerance and a lower cGMP increase.
- The vasodilator effect of 2MN may involve mechanisms beyond guanylate cyclase stimulation.
- These findings suggest 2MN could offer a more sustained therapeutic benefit in cardiovascular conditions.
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