Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

Article Details

Citation

Munzel T, Steven S, Daiber A

Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

Vascul Pharmacol. 2014 Dec;63(3):105-13. doi: 10.1016/j.vph.2014.09.002. Epub 2014 Oct 14.

PubMed ID
25446162 [ View in PubMed
]
Abstract

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Isosorbide mononitrateGuanylate cyclase soluble subunit alpha-2ProteinHumans
Yes
Activator
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
Isosorbide mononitrateAlcohol dehydrogenase class-3ProteinHumans
No
Substrate
Details
Isosorbide mononitrateGlutathione S-transferase Mu 1ProteinHumans
No
Substrate
Details
Isosorbide mononitrateXanthine dehydrogenase/oxidaseProteinHumans
No
Substrate
Details
Drug Reactions
Reaction
Details
Drug Interactions
DrugsInteraction
Amyl Nitrite
Avanafil
Avanafil may increase the hypotensive activities of Amyl Nitrite.
Erythrityl tetranitrate
Avanafil
Avanafil may increase the hypotensive activities of Erythrityl tetranitrate.
Isosorbide
Avanafil
Avanafil may increase the hypotensive activities of Isosorbide.
Isosorbide dinitrate
Avanafil
Avanafil may increase the hypotensive activities of Isosorbide dinitrate.
Nitroglycerin
Avanafil
Avanafil may increase the hypotensive activities of Nitroglycerin.