Uloga kalijumovih kanala u efektima rezveratrola i naringenina na izolovanim venskim krvnim sudovima čoveka i pacova

Abstract

Polifenoli su sloţena biljna, polusintetska i sintetska organska jedinjenja. Hrana sadrţi smešu različitih polifenola, a posebno voće i povrće, zeleni i crni čaj, crveno vino i dr. Nedavna istraţivanja govore u prilog značajne uloge polifenola u prevenciji kardiovaskularnih oboljenja, karcinoma, osteoporoze, neurodegenerativnih oboljenja i diabetes mellitusa. Najveći broj dokaza za to potiče iz in vitro i studija na ţivotinjama. Rezveratrol, polifenol iz crvenog groţđa i crvenog vina, je najviše proučavan polifenol. Za razliku od njega, naringenin, citrusni polifenol, pripada manje proučavanoj grupi polifenola, flavonoidima. Međutim, mehanizam vazodilatatornog i antivazokonstriktornog dejstva ovih polifenola na venskim krvnim sudovima još uvek nije proučen. Postoje dokazi da polifenoli mogu da aktiviraju kalijumove kanale (K-kanale) u glatkim mišićima arterijskih krvnih sudova i da na taj način dovedu do vazodilatacije. Ciljevi našeg istraţivanja bili su: a) da proučimo moguće antivazokonstriktorno i vazodilatatorno dejstvo rezveratrola i naringenina na izolovanoj portnoj veni pacova i humanoj pupčanoj veni, koje su prethodno kontrahovane na različite načine; b) da identifikujemo različite K-kanale vaskularnog glatkog mišića portne vene pacova i humane pupčane vene; c) da ispitamo da li K-kanali imaju značajnu ulogu u antivazokonstriktornom i vazodilatatornom dejstvu rezveratrola i naringenina; d) da proučimo postojanje dodatnog mehanizma dejstva rezveratrola i naringenina, koji je nezavisan od K-kanala, na izolovanim venskim krvnim sudovima. Kontrakcije portne vene pacova bez endotela izazivali smo pomoću električne stimulacije (ES), noradrenalina (NA), adenozin 5-trifosfata (ATP), rastvorom koji sadrţi visoku koncentraciju jona K+, kao i pomoću CaCl2...

Polyphenols are complex plant-derived, semisynthetic or synthetic organic compounds. Foods contain complex mixtures of polyphenols, especially fruit and vegetables, green tea, black tea, red wine, etc. Recent studies strongly supports a role for polyphenols in the prevention of cardiovascular diseases, cancers, osteoporosis, neurodegenerative diseases, diabetes mellitus etc. Much of the evidence on the prevention of diseases by polyphenols is derived from in vitro or animal experiments. Resveratrol, polyphenol from grapes and red wine, is the most studied polyphenol, while naringenin, citrus polyphenol, belongs to the most studied group of polyphenols, flavonoids. However, the mechanisms of vasodilator and antivasoconctrictor effects of these polyphenols on venous blood vessels are not established. There are suggestions that polyphenols could activate potassium channels (K-channels) in the vascular smooth muscle cells and to induce relaxation of blood vessels. The aims of our research were: a) to analyze potential antivasoconstrictor and vasodilator effects of resveratrol and naringenin in the isolated rat portal vein and human umbilical vein, previously contracted in different ways; b) to identify K-channels in the vascular smooth muscle of human umbilical vein and rat portal vein; c) to examine whether K- channels play an important role in the antivasoconstictor and vasodilator effects of resveratrol and naringenin; d) to analyze additional potassium channel-independent effects of resveratrol and naringenin in the isolated venous blood vessels. Contractions of rat portal vein without endothelium were produced by electrical field stimulation of perivascular nerves (EFS), norepinephrine (NE), adenosine 5′-triphosphate (ATP), high K+ solution and by CaCl2 in Ca2+-free and high K+, Ca2+- free solution. In order to test whether resveratrol opens big calcium-sensitive (BKCa) channels, its effects were compared with those of NS 1619, a selective opener of BKCa channels...