Mechanism of the endothelium-dependent vasodilation and the antihypertensive effect of Brazilian red wine.
The mechanisms involved in the cardioprotector effect of red wine have not yet been completely elucidated but probably an endothelium-dependent vasodilator action may play a significant role in this effect. Experiments were undertaken to determine whether a Brazilian red wine (BRW) induces vasodilation in the mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in rats with NO-deficient hypertension. In MVB precontracted with norepinephrine, BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW. In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin, the effect of BRW was significantly reduced. However, this effect is not affected by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine, pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did not change the vasodilator effect of BRW. Chronic oral administration of BRW induced a significant reduction in systolic, mean and diastolic arterial pressure in rats with L-NAME hypertension. The present results demonstrated that vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect of red wine demonstrated in the present study may play a significant role on the cardioprotective action of chronic red wine consumption.
Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. demoura@uerj.br
Roberto Soares
RS
de Moura
Daniel Z
DZ
Miranda
Ana Cláudia A
AC
Pinto
Raquel F
RF
Sicca
Marcelo A V
MA
Souza
Lorna M S
LM
Rubenich
Lenize C R M
LC
Carvalho
Bruno M
BM
Rangel
Tania
T
Tano
Socorro V F
SV
Madeira
Angela C
AC
Resende
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000284:Administration, Oral; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001938:Brazil; D018999:Charybdotoxin / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000502:physiology*; D005419:Flavonoids / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology; D010477:Perfusion; D010636:Phenols / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology; D059808:Polyphenols; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D011738:Pyrilamine / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014920:Wine / Q000009:adverse effects; D015016:Yohimbine / Q000494:pharmacology
C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D005419:Flavonoids; D010069:Oxadiazoles; D010636:Phenols; D059808:Polyphenols; D011799:Quinazolines; D011810:Quinoxalines; D003840:Deoxycholic Acid; D018999:Charybdotoxin; D001030:Apamin; D015016:Yohimbine; D011189:Potassium Chloride; D001285:Atropine; C065679:icatibant; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D011738:Pyrilamine; D003000:Clonidine; D000109:Acetylcholine; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin