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Planta Med 2013; 79(06): 465-467
DOI: 10.1055/s-0032-1328293
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

Quercetin Mitochondriotropic Derivatives Antagonize Nitrate Tolerance and Endothelial Dysfunction of Isolated Rat Aorta Rings

Miriam Durante
1   Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy
,
Giampietro Sgaragli
1   Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy
,
Lucia Biasutto
2   CNR Istituto di Neuroscienze, Padova, Italy
3   Dipartimento di Scienze Biomediche, Università degli Studi di Padova, Padova, Italy
,
Andrea Mattarei
2   CNR Istituto di Neuroscienze, Padova, Italy
4   Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Padova, Italy
,
Fabio Fusi
1   Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy
› Author Affiliations
Further Information

Publication History

received 28 December 2012
revised 04 February 2013

accepted 05 February 2013

Publication Date:
11 March 2013 (online)

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Abstract

Chronic use of glyceryl trinitrate is limited by serious side effects, inter alia tolerance and endothelial dysfunction of coronary and resistance arteries. The natural flavonoid quercetin has been shown to counteract the development of glyceryl trinitrate tolerance in vitro. Two mitochondriotropic, 4-O-triphenylphosphoniumbutyl derivatives of quercetin (QTA-3BTPI and Q-3BTPI) were compared to quercetin for protection against glyceryl trinitrate-induced tolerance and endothelial dysfunction of isolated rat aorta rings. Both QTA-3BTPI and Q-3BTPI significantly counteracted the reduced vascular responsiveness to both glyceryl trinitrate and acetylcholine caused by prolonged exposure of the vessel to glyceryl trinitrate itself, their potency being much greater than that of quercetin. QTA-3BTPI, however, turned out to cause endothelial dysfunction per se. Since Q-3BTPI antagonized in vitro nitrate tolerance and endothelial dysfunction of vessels, this encourages assessing whether this effect is displayed also in vivo during long-term glyceryl trinitrate treatment.

Key words

rat aorta rings - glyceryl trinitrate tolerance - endothelial dysfunction - quercetin

Supporting Information

 

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