Mechanisms Underlying the Vasorelaxant Effect Induced by Proanthocyanidin-Rich Fraction From Croton celtidifolius in Rat Small Resistance Arteries

Abstract

Abstract. Proanthocyanidins are condensed tannins present in fruits, vegetables, and flowers, consumed in the human diet. These compounds are believed to decrease coronary heart disease. The present study was designed to investigate the relaxing effects of a proanthocyanidin-rich fraction (PRF) obtained from Croton celtidifolius BAILL (Euphorbiaceae) barks in rat mesenteric arterial bed (MAB) and isolated mesenteric artery (MA). In the MAB pre-contracted with phenylephrine (Phe), PRF (0.1 -100 µg) induced a concentration-dependent relaxation of 73% (compared to the control). This effect was significantly reduced by the nitric oxide (NO) synthase inhibitor N ω -nitro-L-arginine (L-NOARG) or high K + solution and completely abolished in vessels perfused with KCl plus L-NOARG. However, the vasorelaxant effect was not altered by indomethacin, atropine, yohimbine, pyrilamine, or K + -channel blockers: BaCl 2 , glibenclamide, ouabain, and 4-aminopyridine. In isolated MA pre-contracted with Phe, PRF also induced a concentration-dependent relaxation (0.1 -30 µg/ mL), which was in turn inhibited by endothelial removal, guanylyl cyclase inhibitor 1H [1,2,3]oxadiazolo [4,3-alpha]quinoxalin, charybdotoxin (ChTx), and ChTx plus apamin. Moreover, the relaxant effect was not altered by HOE140 and apamin given alone. The present study demonstrates that the vasorelaxing effect of PRF is dependent upon the NO-cGMP pathway in combination with hyperpolarization due to activation of Ca 2+-dependent K + channels.

Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K+Channel Activations

“…21) 4-Aminopyridine and BaCl 2 significantly shifted the vasorelaxation curve to the right, and paxillin, apamin, and glybenclamide had a tendency to inhibit this effect. As DalBo et al 8) reported, BK Ca 2þ þ SK Ca 2þ inhibitors abolished the relaxation of procyanidins, although less abolition was observed for each inhibitor alone. This implies that blocking both small and large-conductance Ca 2þ -activated K þ channels can abolish AP relaxation (the combination experiment not done).…”

“…Dalbo et al 8) also reported that endothelium-dependent vasorelaxation of procyanidins from Croton celtidifolius was involved in the activation of Ca 2þ -dependent K þ channels. In contrast, Kwan et al 9) found that vasorelaxation due to procyanidin-rich extract was caused by the opening of multiple K þ channels.…”

“…4,5) Intact absorption of AP led us to do further experiments regarding the preventive effects of AP against metabolic syndromes such as hypertension. Recent reports regarding procyanidins [6][7][8] have provided useful information that they play potential roles in regulating vessel functions. Magos et al 6) concluded that the vasorelaxation effect of antihypertensive procyanidins from Guazuma ulmifolia due to NO-mediated pathways as tannins were involved in the NO/cGMP pathway.…”

Activation of Endothelial Nitric Oxide Synthase by Proanthocyanidin-Rich Fraction From Croton celtidifolius (Euphorbiaceae): Involvement of Extracellular Calcium Influx in Rat Thoracic Aorta

“…In a recent study, we observed that proanthocyanidinrich fraction (PRF) mediates an endothelium-dependent vasorelaxant effect involving the NO-cGMP pathway and hyperpolarization induced by K Ca2+ channels activation in rat small resistance arteries (21). The aim of the current investigation is to determine the mechanisms of the PRF-induced vasodilator effect, using rat thoracic aorta.…”

Anticancer activity of flavonol and flavan-3-ol rich extracts fromCroton celtidifoliuslatex

“…Phytochemical studies of C. celtidifolius bark indicate the presence of cyclitols such as 1L-1-O-methyl-myo inositol, neo-inositol and sitosterol (Mukherjee & Axt, 1984), catechins and gallocatechins, proanthocyanidins (DalBó et al, 2008;Nardi et al, 2003), alkaloids and saponins (Amaral & Barnes, 1997). In Croton species containing red latex, only proanthocyanidin polymers of varying molecular weight have been characterized, comprising almost 90% of the red latex dry weight (Salatino et al, 2007).…”