Mechanisms underlying the vasorelaxant effect of (-)-epicatechin and procyanidin B2 on human internal thoracic artery and human saphenous vein

[G. S. Janković]

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Farmacija - Farmakologija / Pharmacy - Pharmacology

Dugotrajan i umeren unos namirnica bogatih polifenolima je u obrnutoj korelaciji sa rizikom od razvoja ateroskleroze. In vitro, nа animalnim modelima, kao i u kratkoročnim kliničkim studijama, pokazano je da antiaterogenom delovanju flavanola značajno doprinose antioksidativni i antiinflamatorni efekat, kao i pozitivan uticaj na endotelnu funkciju. Pored toga, značajnu ulogu u kardioprotektivnom efektu flavanola ima i vazorelaksantno delovanje, pokazano na više tipova animalnih krvnih sudova. Cilj ove studije bio je da se ispita mehanizam vazorelaksantnog dejstva dva flavanola, (-)-epikatehina i procijanidina B2 na izolovanoj humanoj unutrašnjoj torakalnoj arteriji i veni safeni. Neiskorišćeni segmenti ispitivanih krvnih sudova uzimani su od pacijenata tokom bajpas operacija. Ispitivanje je rađeno u kupatilu za izolovane organe. Preparati sa i bez endotela prekontrahovani su fenilefrinom nakon čega su konstruisane koncentracijski-zavisne krive relaksacije sa ili bez prisustva različitih blokatora/inhibitora ili njihovih kombinacija. Naši rezultati su pokazali da (-)-epikatehin i procijanidin B2 prouzrokuju snažnu koncentracijski-zavisnu relaksaciju ispitivanih krvnih sudova. Delovanje (-)-epikatehina je endotelnezavisno, a efekat procijanidina B2 u značajnoj meri zavistan od prisustva intaktnog endotela i aktivacije azot-monoksid (NO)/ciklični gvanozin monofosfatnog (cGMP) puta. Različiti tipovi kalijumovih (K+) kanala, i to voltažno zavisni (KV), ATP-zavisni (KATP) i Ca2+-zavisni (KCa) su uključeni u mehanizam dejstva (-)-epikatehina i procijanidina B2. Vazorelaksantnom delovanju obe supstance značajno doprinosi i uticaj na promet ekstra- i intracelularnog Ca2+. S obzirom da funkcionalno stanje endotela i glatkih mišićnih ćelija značajno utiče na postoperativnu prohodnost graftova, primena (-)-epikatehina i procijanidina B2, čije kardioprotektivno dejstvo uključuje poboljšanje endotelne funkcije i vazorelaksantno dejstvo, može imati veoma značajnu ulogu u prevenciji kardiovaskularnih oboljenja.

It has been observed a strong negative correlation between long-term and moderate intake of polyphenol-rich foods and the atherosclerosis development. The various animal models, in vitro assays and short-term clinical studies have demonstrated flavanols antiatherogenic activity owing to their antioxidant, anti-inflammatory and endothelial protective function. Certainly, vasorelaxant activities, documented on several types of blood vessels of animal origin, greatly contribute to their cardioprotective effects. The principal aim of this study was to investigate the mechanism of vasorelaxant effect of (-)-epicatechin and procyanidin B2 on isolated human internal thoracic artery and human saphenous vein. Discarded segments of the internal thoracic artery and saphenous vein were collected from patients undergoing coronary artery bypass grafting. The investigation was performed in an isolated organ bath. The preparations with and without endothelium were precontracted with phenylephrine, followed by construction of concentration-response curves in the presence or absence of different blockers/inhibitors or their combinations. Our results showed that (-)-epicatechin and procyanidin B2 cause a strong concentrationdependent relaxation of the examined blood vessels. The action of (-)-epicatechin is endotheliumindependent, and the effect of procyanidin B2 is significantly dependent on the presence of intact endothelium and activation of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. Different types of potassium (K+) channels, voltage-gated (KV), ATP-gated (KATP) and Ca2+- gated (KCa) are involved in the mechanism of action of (-)-epicatechin and procyanidin B2. The vasorelaxant effect of both substances is significantly contributed by the influence on the turnover of extra- and intracellular Ca2+. Given that the functional state of the endothelium and smooth muscle cells significantly affects the postoperative grafts patency , using (-)-epicatechin and procyanidin B2, whose cardioprotective effect includes improvement of endothelial function and vasorelaxant effect, could play a very significant role in the prevention of cardiovascular disease.

flavanoli, (-)-epikatehin, procijanidin B2, vazorelaksacija, humana unutrašnja torakalna arterija, humana vena safena, NO, K+ kanali, promet Ca2+

flavanols, (-)-epicatechin, procyanidin B2, vasorelaxation, human internal thoracic artery, human saphenous vein, nitric oxide, potassium channels, calcium turnover

615.22.015(043.3)

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