Role Of Endothelium In Relaxation Research Articles

Spasmolytic effect of curcumin on goat ruminal artery is endothelium independent and by activation of sGC

The aim of the present work was to study the mechanism of action of curcumin in vasomotion of a physiologically important artery of ruminant i.e. ruminal artery. ACh and SNP were used to study the role of endothelium in relaxation of this artery. Vasorelaxatation by curcumin was studied in a dose dependent manner, on rings precontracted with 5-hydroxy tryptamine and noradrenalin, in presence and absence of L-NAME, 4AP, ODQ and 4AP+ODQ combination. SNP (1ηM–100μM) produced a significant relaxation compared to ACh (0.1–100μM) on 5-HT (10μM) and NA (10μM) induced contraction in endothelium intact rings. Curcumin (10ηM–100μM) relaxed the vascular rings in dose dependent manner with maximal relaxation up to 20.94% and 13.81% in 5-HT and NA induced contraction, respectively which was potently blocked by ODQ (10μM) and combination of 4AP and ODQ (10μM) but 4AP (10μM) and L-NAME (100μM) alone could not block the relaxation and interestingly we observed a slight increase in the tension at higher dose of the agonist (>10μM). Therefore in goat ruminal artery, curcumin at least in part, act via direct activation of sGC mediated cGMP pathway followed by opening of K+ ion channel. However other mechanisms may not be ruled out.

Differential role of endothelium in hawthorn fruit extract-induced relaxation of rat cerebral, coronary, carotid, and aorta

The present study was aimed to examine the role of endothelium in the relaxant effect of hawthorn fruit extract of Crataegus pinnatifida in four different types of rat arteries, posterior cerebral communicating artery, right descending coronary artery, common carotid artery, and aorta. In <TEX>$9,11-dideoxy-11{\alpha}$</TEX>, <TEX>$9{\alpha}-epoxy-methanoprostaglandin$</TEX> <TEX>$F_{2{\alpha}}$</TEX> (U46619)-preconstricted arterial rings except for aorta, the extract produced endothelium-independent relaxations with similar potency. This relaxation was unaffected by pretreatment with <TEX>$100\;{\mu}M\;N^G-nitro-L-arginine$</TEX> methylester (L-NAME, the nitric oxide synthase inhibitor), <TEX>$3\;{\mu}M$</TEX> 1H-[l,2,4]oxadiazolo<TEX>$[4,2-{\alpha}]$</TEX>quinoxalin-1-one (ODQ, the guanylate cyclase inhibitor), or <TEX>$10\;{\mu}M$</TEX> indomethacin (the cyclooxygenase inhibitor). Putative <TEX>$K^+$</TEX> channel blockers (charybdotoxin plus apamin or glibenclamide) did not affect the extract-induced relaxation in cerebral or coronary artery rings. In contrast, in rat aortic rings the extract produced significantly smaller relaxant response in endothelium-denuded rings than that in endothelium-intact rings. Pretreatment with L-NAME or ODQ abolished the extractinduced endothelium-dependent aortic relaxation, whilst indomethacin <TEX>$(3\;{\mu}M)$</TEX> had no effect. The present results indicate that hawthorn fruit extract possesses a vasorelaxing effect in cerebral, coronary and carotid arteries and this effect is independent of the presence of a functional endothelium. However, the extract-induced endothelium-dependent relaxation in rat aorta was mediated through endothelial nitric oxide and cyclic GMP-dependent mechanisms, suggesting that active components in the extract may act on endothelium to stimulate release of nitric oxide in large conduit arteries of the rats.

Role of endothelium in magnesium-induced relaxation of rat aorta

The role of endothelium in the relaxation of rat aortic smooth muscle to raised extracellular magnesium concentration (Mg2+)o has been examined. Following contractile responses to norepinephrine (NE) or high-K+ in Mg2+-free media, cumulative increases in (Mg2+)o caused concentration-dependent relaxations in intact (+E) as well as endothelium-denuded (-E) strips. In NE-stimulated strips, Mg2+-induced relaxation was significantly greater in +E strips, whereas the reverse was the case in K+-stimulated strips. Bay K8644, a Ca2+ channel agonist, did not modify Mg2+-induced relaxation in NE-stimulated strips, but significantly attenuated the relaxation in K+-stimulated strips in the order: -E greater than +E. The results suggest that Mg2+-induced relaxation of rat aorta is associated, at least in part, with the release of an endothelium-derived relaxant factor in receptor-mediated, but not in depolarisation-dependent contractions.