Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols.
OBJECTIVE
At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure-activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state.


METHODS
The effects of two catechins, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium.


RESULTS
At resting tension, endothelium-intact preparations, EGCG and EP (0.01-10 μM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 μM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 μM) precontracted, endothelium-intact preparations, EGCG and EP (0.01-10 μM), induced a concentration-dependent vasorelaxation, reaching significance at 1 μM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 μM)-induced tone. In endothelium-intact precontracted preparations, Nω nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01-10 μM). At high concentrations, EGCG and EP (100 μM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA.


CONCLUSIONS
Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.
Department of Internal Medicine and Public Health, University of L'Aquila, Viale S. Salvatore, Delta 6 Medicina, 67100, Coppito, AQ, Italy.
Annalisa
A
Aggio
Davide
D
Grassi
Eugenia
E
Onori
Antonio
A
D'Alessandro
Francesco
F
Masedu
Marco
M
Valenti
Claudio
C
Ferri
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase