Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition

Lo, Yi-Ching; Tsou, Huei-Hsia; Lin, Rong-Jyh; Wu, Deng‐Chyang; Wu, Bin–Nan; Lin, Young-Tso; Chen, Ing‐Jun

doi:10.1016/j.lfs.2004.10.009

Cited by 23 publications

(23 citation statements)

References 33 publications

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“…In particular, it can lead to excessive vasoconstriction and hypertension, inflammation, leukocyte adhesion, thrombosis, atherosclerosis, and proliferation of vascular smooth muscle cells. 6 Many reports suggested that the flavonoid family of compounds, of which SCU is a member, can modulate tone in vasculature by endothelium-derived NO and counteract any dysfunction of endothelium associated with cardiovascular 1,[28][29][30] Our report of endothelial-dependent vasodilation by SCU is in agreement with reports about other flavonoids in aortic preparations. 1,[29][30][31] Most of the flavonoids tested were found to be more potent in relaxing contractions induced by receptor agonists, including PE, than those produced by depolarization, and the relaxation ability was mostly inhibited by pretreatment with L-NAME.…”

Section: Discussionsupporting

confidence: 89%

Nitric Oxide and Catalase-sensitive Relaxation by Scutellarin in the Mouse Thoracic Aorta

Lust²,

Bofferding³

et al. 2009

Journal of Cardiovascular Pharmacology

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The vascular activity of scutellarin (SCU), a flavonoid isolated from a Chinese traditional medicinal plant, was investigated in isolated thoracic aortic rings of mice. SCU-induced dose-dependent relaxation of phenylephrine (1 microM) stimulated contractions. This relaxation was reduced by endothelium removal, significantly reduced by both the nitric oxide synthase inhibitor (Nomega-nitro-L-arginine methylester, 300 microM) and slightly limited by the soluble guanylyl cyclase inhibitor (1 H-[1,2,4] oxidazolol [4,3-a] quinoxalin-1-one, 100 microM). The catalase inhibitor (3-amino-1,2,4-triazole, 50 mM) augmented the constriction and blocked the lowest SCU concentration relaxation, whereas catalase addition was without effect. Preincubation with 300 and 1000 microM SCU significantly suppressed the contractile dose-response to phenylephrine, causing both a significant rise in half maximal effective concentration and a decrease in the maximal developed force. Western blot analysis showed that SCU inhibition of contraction was independent of reductions in myosin light chain phosphorylation. These results suggested that SCU relaxation was predominantly endothelium dependent and likely involved the catalase-sensitive nitric oxide synthase signaling pathway, without loss of myosin phosphorylation. The potential clinical use of SCU may prove to be effective in increasing vasoreactivity, independently of smooth muscle contractile activity that is mediated by the 20-kDa myosin light chain phosphorylation.

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Section: Discussionsupporting

confidence: 89%

Nitric Oxide and Catalase-sensitive Relaxation by Scutellarin in the Mouse Thoracic Aorta

Lust²,

Bofferding³

et al. 2009

Journal of Cardiovascular Pharmacology

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“…Although these channels can present physiological particularities in different smooth muscle preparations, the effects of 4-AP on the oscillatory contractions in isolated aortic rings of SAD rats are mild. Although the concentration used in this study is able to block K v , 8,30) 4-AP increased the tension only, but it did not alter the frequency and amplitude of the oscillations.…”

Section: Discussionmentioning

confidence: 51%

Effects of K+ Channel Modulators on Oscillatory Contractions in Sinoaortic Denervated Rat Aortas

Rocha

Bendhack

2007

Biological & Pharmaceutical Bulletin

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Sinoaortic denervated (SAD) rats present arterial pressure lability without sustained hypertension. We investigated the relation between sinoaortic denervation and the occurrence of oscillatory contractions in SAD rat aortas, as well as the effect of various K ؉ channel modulators on these oscillations. Aortas were removed and concentration-effect curves to phenylephrine (0.01 to 10 m mM) were constructed in arteries from SAD and Shamoperated rats in order to verify the occurrence of oscillations. We also evaluated the effects of various K ؉ channel modulators on these oscillations. Only SAD rat aortas exhibited oscillatory contractions.

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“…This indicates that vasorelaxant effect of compound (8a) depends on sGC-cGMP signalling, at least partially. sGC and cGMP are located not only in endothelium but also in vascular smooth muscle cells and also PDE isoforms are differentially distributed both in endothelial and vascular smooth muscle cells 16,18,19 . In vascular smooth muscle, PDE1 (hydrolyzes cGMP and cAMP) and PDE3 (hydrolyzes cAMP preferentially but not exclusively) isoenzymes play an important role as modulators of rat aorta contractility.…”

Section: Discussionmentioning

confidence: 99%

Relaxant effects of selected sildenafil analogues in the rat aorta

Kubacka

Mogilski

Filipek

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of sulfonamide derivatives of pyrazolo [4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their relaxant effects in the rat aorta. Evaluation of prepared derivatives demonstrated that compound (8a) is probably a non-selective phosphodiesterase (PDE) inhibitor, as it induced aortic relaxation through endothelium-independent mechanism.

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Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition

Cited by 23 publications

References 33 publications

Nitric Oxide and Catalase-sensitive Relaxation by Scutellarin in the Mouse Thoracic Aorta

Nitric Oxide and Catalase-sensitive Relaxation by Scutellarin in the Mouse Thoracic Aorta

Effects of K+ Channel Modulators on Oscillatory Contractions in Sinoaortic Denervated Rat Aortas

Relaxant effects of selected sildenafil analogues in the rat aorta

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