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

Abstract

Abstract. The present study investigates the mechanisms related to the endogenous nitric oxide synthase (eNOS) activation in the relaxant effects of a proanthocyanidin-rich fraction (PRF), obtained from Croton celtidifolius BAILL barks, in rat thoracic aorta rings with endothelium. In vessels pre-contracted with phenylephrine (Phe), PRF (0.1 -100 μg / mL) induced a concentration-dependent relaxation. This effect was significantly reduced by endothelium denudation, by N ω -nitro-L-arginine, and by 1H[1,2,3]oxadiazolo [4,3-alpha]quinoxalin. However, the vasorelaxant effect was not altered by indomethacin, atropine, tetraethylammonium, and charybdotoxin plus apamin. In thoracic aorta rings pre-contracted with phorbol-12,13-dibuyrate, PRF also induced a concentration-dependent relaxation. The PRF-induced relaxation disappeared in the absence of extracellular calcium in the medium and decreased significantly in the presence of lanthanum. A sulfhydryl alkylating agent, N-ethylmaleimide, and a phospholipase C (PLC) blocker, neomycin, significantly decreased PRF-induced vasorelaxation. In vessels pre-contracted with Phe, the PRFinduced vasorelaxant effect was not altered by quinacrine and ONO-RS-082, genistein and thyrphostin A-23, GF109203, and pertussis toxin and cholera toxin. The results suggest that the PRF-induced vasorelaxant effect is endothelium-dependent and involves the NO / cGMP pathway. We hypothesize that the activation of eNOS is due to an increase of intracellular calcium derived from PLC activation and an N-ethylmaleimide sensitive pathway.

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

“…Recent reports regarding the procyanidin-induced relaxation mechanism concluded that relaxation results from hyperpolarization through Ca 2þ -dependent BK Ca 2þ activation. 8,23) By contrast, Kwan et al 9) clearly showed the involvement of vasorelaxant procyanidin-rich extract in the opening of multiple K þ channels including BK Ca 2þ , K V and K ir , consistently with our results. It is likely that whether procyanidins involve the opening of Ca 2þ -dependent or -independent K þ channels or both is dependent on multiple active procyanidins of different origin, since procyandins are heterogeneous condensed tannins of catechins and/or epicatechins.…”

Blood pressure-lowering properties of chokeberry (Aronia mitchurinii, var. Viking)

“…A number of animal and human studies have suggested a blood pressurelowering effect of flavonoids from plant sources including soy, red clover, and cocoa (Ding et al, 2006;Howes et al, 2003;Rivas et al, 2002). Vasorelaxing properties of polyphenols appear to be endothelium-dependent and recent studies have strongly suggested that the prime mechanism involves enhanced activation and/or increased expression of endothelial nitric oxide synthase (eNOS) (Appeldoorn et al, 2009;DalBó et al, 2008). Thus, ACE inhibition is not essential for vasorelaxation in agreement with the present study.…”

Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats

“…We have demonstrated that the PRF presents antinociceptive effects against chemical and thermal noxious stimuli, with involvement of capsaicin‐sensitive C‐fibres and dopamine D 2 receptors [9,10] . Moreover, PRF induces endothelium‐dependent vasorelaxant effects via the NO–cGMP pathway and hyperpolarisation due to the activation of Ca 2+ ‐dependent K + channels in the small‐resistance arteries of rats [11,12] …”