Estudios científicos

Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels

Abstract:

PURPOSE: Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles.
METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrol-induced diameter changes were recorded by videomicroscopic techniques.
RESULTS: Retinal arterioles (65 +/- 3 microm) dilated dose dependently in response to resveratrol (1-50 microM). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N(G)-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K(+) channel blocker, tetraethylammonium (TEA), and a large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K(+) channels and voltage-gated K(+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol.
CONCLUSIONS: Resveratrol elicits endothelium-dependent and -independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase (NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BK(Ca) channels in smooth muscle contributes to the endothelium-independent dilation caused by resveratrol. A better understanding of the action of resveratrol on retinal vasculature may help shed light on its therapeutic potential for retinal vascular disease.
 

Comentarios divulgativos:

El resveratrol, una fitoalexina presente en las uvas y el vino tinto se ha demostrado que ejerce beneficios cardiovasculares, pero su acción en la microcirculación retiniana sigue siendo desconocida. En este estudio, los efectos directos y el mecanismo subyacente de la acción vasomotora del resveratrol se examinaron en las arteriolas de la retina.
Se aislaron las arteriolas retinianas de porcino sin presión de flujo para el estudio in vitro. Los cambios de diámetro inducidos por el resveratrol se registraron por medio de técnicas de videomicroscopia.
La eliminación del endotelio redujo esta dilatación en un 50%. La inhibición del óxido nítrico (NO) sintasa (por L-NAME; N (G)-nitro-éster metílico de la L-arginina) y el bloqueo de la guanilato ciclasa soluble (por ODQ; 1H-1 ,2,4-oxadiazolo [4,3 -a] quinoxalin-1-ona) produjo una inhibición similar a la producida por denudación. Sin embargo, la respuesta resveratrol no se vio afectada por la indometacina (un inhibidor de la ciclooxigenasa) y el sulfaphenazole (un inhibidor de la epoxygenasa).: El resveratrol produce la dilatación del endotelio dependiente e independiente-de las arteriolas de la retina. La dilatación dependiente del endotelio está mediada por el NO libre, probablemente a través de la NO sintasa (NOS) por la vía de la activación de ERK y la consecuente activación de la adenilato ciclasa soluble. La activación los canales en el músculo liso de BK (Ca) contribuye a la dilatación del endotelio independiente causados por el resveratrol. Una mejor comprensión de la acción del resveratrol en la vascularización retiniana puede ayudar a arrojar luz sobre su potencial terapéutico para la enfermedad vascular de la retina.