Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat. 2. Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and alpha1-adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation. 3. The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L-NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium-intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium-denuded arteries. While melatonin does not appear to modulate agonist-induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress. 4. When the Ca2+-activated K+ channel opener, NS 1619 (10 microM), was present, potentiating effects of melatonin were restored in endothelium-denuded vessels. However, addition of the opener of ATP-sensitive K+ channels, cromakalim (3 microM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca2+-activated K+ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca2+-activated K+ channels to produce its potentiating effects. 5. Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca2+-activated K+ channels. Our findings suggest that melatonin inhibits endothelial K+ channels to decrease flow-induced release of nitric oxide as well as block smooth muscle K+ channels to enhance vascular tone.
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PMID:Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors. 960 58

The present study describes the role of endothelium in the vascular response to purified acteoside from Ligustrum purpurascens in rat mesenteric arteries. In endothelium-intact rings, acteoside (3-50 micromol/L) enhanced phenylephrine-induced contraction without affecting the maximum response. This enhancement was absent in endothelium-denuded rings. Pretreatment with nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA, 100 micromol/L) and N(G)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L), or a selective guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ, 10 micromol/L), increased both the sensitivity of vasoconstriction to phenylephrine and the maximal response. The enhancing effect of acteoside (30 micromol/L) was abolished in the presence of L-NAME, L-NNA, or ODQ. Tetraethylammonium (TEA(+), 3 mmol/L), a putative K(+) channel blocker, also abolished the effect of acteoside. CaCl2 (0.01-10 mmol/L) induced contractions in 50 mmol/L K(+)-containing Krebs solution. Neither acteoside nor TEA(+) affected CaCl2-induced contraction in elevated K(+) solution. Acteoside (30 micromol/L) attenuated acetylcholine-induced endothelium-dependent relaxation. Acteoside did not influence relaxation induced by exogenous NO donors, hydroxylamine or sodium nitroprusside, in endothelium-denuded rings. Acteoside did not alter endothelium-independent relaxation induced by forskolin or NS 1619. The present results indicate that acteoside enhanced the evoked vasoconstriction, mainly through inhibition of endothelial NO production/release and inhibition of NO-mediated TEA(+)-sensitive activation of K(+) channels.
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PMID:Enhancement of contraction of rat mesenteric artery by acteoside: role of endothelial nitric oxide. 1214 58

Large-conductance calcium-activated potassium channels (BK) of smooth muscle play a role in the relevant modulation of vascular tone, due to their calcium- and voltage-dependent mechanisms of activation. A potential role of endothelial BK channels has also been suggested by approaches on endothelial cell cultures. However, no functional study, aimed at evaluating the contribution of endothelial BK channels to the effect of BK-openers, has been reported. Resveratrol and NS 1619, BK-openers, have been tested on endothelium-intact and -denuded aortic rings. Furthermore, the effects of high depolarisation of potassium channel blockers TEA (Tetraethylammonium), 4-AP ( 4-Aminopyridine) and IbTX (Iberiotoxin) and of inhibitors of NO-pathway (L-NAME and ODQ) have been evaluated. The presence of endothelium increased the vasorelaxing potency of BK-openers. This potentiation was eliminated by L-NAME and ODQ. TEA, 4-AP, IbTX and high depolarisation had modest or no antagonist influence on resveratrol in endothelium-denuded aortic rings. The effects of NS 1619 on endothelium-denuded aortic rings were not affected by IbTX, and were modestly antagonised by TEA, 4-AP and high depolarisation. In intact endothelium vessels, TEA, IbTX and 4-AP antagonised the vasorelaxing effect of the two BK-activators. A BK-mediated release of endothelial NO seems a very important factor, determining a strong influence on vasodilator profile of BK-openers. Therefore, an eventual therapy with a BK-opener could promote a series of cardiovascular impacts not confined to the only direct vasorelaxing effects, but also due to a significant contribution of endothelial NO.
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PMID:Functional contribution of the endothelial component to the vasorelaxing effect of resveratrol and NS 1619, activators of the large-conductance calcium-activated potassium channels. 1720 88