title: Resveratrol augments nitric oxide generation and causes store calcium release in chromaffin cells.
abstract: The cardiovascular protecting effect of the grape fruit trans-resveratrol has been explained among other factors, through augmentation of nitric oxide (NO) production in cardiovascular tissues. Another effect of low resveratrol concentration is the inhibition of single-vesicle quantal release of catecholamine from bovine adrenal chromaffin cells, that was recently suggested to be an additional factor contributing to its beneficial cardiovascular effects. We have investigated here the effects of a low concentration of trans-resveratrol (1 μM) on Ca(2+) and NO signaling pathways in bovine chromaffin cells, in an attempt to understand the mechanism underlying its previously reported inhibitory effects on quantal secretion. In cells loaded with fura-2 acetoxymethyl ester (fura-2), we have found that 1 μM resveratrol produces a transient elevation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)). This Ca(2+) transient was drastically reduced when the Ca(2+) store was depleted by ryanodine and dantrolene; it was also inhibited by N(ω)-nitro-l-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Furthermore, the Ca(2+) transient was mimicked by NO donor S-nitroso-N-acetyl-penicillamine (SNAP). Resveratrol also enhanced the production of nitrites and NO, and L-NAME blocked both responses; in contrast, augmentation by SNAP of nitrites and NO was unaffected by ODQ and was only partially inhibited by L-NAME. On the basis of these results, we are proposing that resveratrol is mitigating the catecholamine surge occurring during stress, through its ability to elicit mild local [Ca(2+)](c) transients and enhanced NO production, that blocks the last steps of exocytosis.
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Spain. jf.padin@gmail.com
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: Padín
authors.forename: Antonio M G
authors.initials: AM
authors.lastname: de Diego
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Fernández-Morales
authors.forename: Cristina
authors.initials: C
authors.lastname: Merino
authors.forename: Marcos
authors.initials: M
authors.lastname: Maroto
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo-Gallardo
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Arranz
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry; D016257:Fura-2 / Q000737:chemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D000077185:Resveratrol; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005456:Fluorescent Dyes; D009573:Nitrites; D013267:Stilbenes; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000077185:Resveratrol; D002118:Calcium; D016257:Fura-2; D019331:NG-Nitroarginine Methyl Ester