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

Rocha, Matheus Lavorenti; Bendhack, Lusiane Maria

doi:10.1248/bpb.30.2098

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…To investigate the influences of the various factors that might contribute to relaxation in the present preparations, we examined the cassiarin A-induced relaxation in the presence or absence of various inhibitors: 1) the cyclooxygenase (COX) inhibitor indomethacin (10 mM) 19,20) ; 2) the nitric oxide synthase (NOS) inhibitor L-NNA (100 mM) 15,21,22) ; 3) the guanylyl cyclase inhibitor ODQ (10 mM) 27,28) ; or 7) the selective BK Ca inhibitor iberiotoxin (100 nM). 22,26,27) Rings were incubated with the appropriate inhibitor(s) for 30 min before the administration of phenylephrine. When required, the endothelium was removed from arterial segments by infusing a CHAPS solution (0.1%, for 60 s), followed by flushing out with KHS.…”

Section: Drugs and Chemicals Phenylephrine Indomethacin Nmentioning

confidence: 99%

Vasodilator Effect of Cassiarin A, a Novel Antiplasmodial Alkaloid from Cassia siamea, in Rat Isolated Mesenteric Artery

Matsumoto

Kobayashi

Ishida

et al. 2010

Biological & Pharmaceutical Bulletin

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Cassia siamea (Leguminosae), a small-to medium-sized tree, is one of the most commonly cultivated trees in Southeast Asia. Different parts of this plant can be used for a variety of medical purposes, giving the plant considerable medicinal potential. In traditional folk medicine, its stem bark is used as a mild, pleasant, safe purgative; a decoction of the bark is given to treat diabetes; a paste is used as a dressing for ringworm and chilblains; the roots are used as an antipyretic; and the leaves are used for the treatment of constipation, hypertension, and insomnia.1,2) A number of compounds, including barakol, emodin, b-and g-sitosterol, lupeol, luteolin, D-pinitol, chromone alkaloids, flavonoid glycosides, and a number of anthraquinones and bianthraquinones, have been isolated from Cassia siamea. 1,3,4) Although members of the genus Cassia are widely distributed in tropical and subtropical regions, where they have long been used in traditional folk medicine, particularly for the treatment of periodic fever and malaria, 5) we only recently have isolated the novel heteroaromatic alkaloid cassiarin A (Fig. 1) from the leaves of Cassia siamea. 6) This was followed a year later by the first total synthesis of cassiarin A, a process completed in eight steps from a known compound, methyl 2,4-dihydroxybenzoate.7) This alkaloid possesses an unprecedented tricyclic skeleton and exhibits potent antiplasmodial activity. 6,8,9) Although we have recently reported that some alkaloids and peptides exhibit not only antiplasmodial activity, but also vasorelaxant activity in the rat aorta, 10-12) the effect of cassiarin A on vascular tone remains unclear. We have very recently found that cassiarin A induces relaxation in the rat thoracic aorta and this was largely due to endotheliumderived nitric oxide (NO).9) However, no study has investigated the effects of cassiarin A on vascular tone in other, smaller arteries. The primary purpose of this study was therefore to test the hypothesis that cassiarin A induces in vitro vascular relaxation in rat mesenteric arteries precontracted with phenylephrine. In addition, we wanted to determine whether the vascular relaxation is endothelium dependent or whether cassiarin A acts directly upon vascular smooth muscle. MATERIALS AND METHODS Drugs and Chemicals, glibenclamide, 4-aminopyridine (4-AP), and tetraethylammonium (TEA) were all purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Acetylcholine chloride was from Daiichi-Sankyo Pharmaceuticals (Tokyo, Japan), 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ) was from Wako (Osaka, Japan), and iberiotoxin was from the Peptide Institute Inc. (Osaka, Japan). Drugs were dissolved in saline, except for glibenclamide [dissolved in dimethyl sulfoxide (DMSO)] and indomethacin (dissolved first in a small amount of Na 2 CO 3 0.1 M solution, then made up to the final volume with distilled water).Cassiarin A was prepared as previously reported. 6) Briefly, leaves of Cassia siamea (collected at the Purwodadi Botanical Garden, Pasuruan, Indon...

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Section: Drugs and Chemicals Phenylephrine Indomethacin Nmentioning

confidence: 99%

Vasodilator Effect of Cassiarin A, a Novel Antiplasmodial Alkaloid from Cassia siamea, in Rat Isolated Mesenteric Artery

Matsumoto

Kobayashi

Ishida

et al. 2010

Biological & Pharmaceutical Bulletin

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Effect of phenylephrine and endothelium on vasomotion in rat aorta involves potassium uptake

et al. 2012

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Vasomotion is defined as the rhythmic contractions in blood vessels, consisting of two components: vasoconstriction and oscillations of the plasma membrane potential. To determine whether vasomotion is associated with changes in K(+) uptake, we measured the effect of phenylephrine (PE) and acetylcholine (ACh) on the K(+) uptake and vascular reactivity in rat aortic rings. We found that the incubation of aortic rings with 10(-7) M PE (210 ± 28 mg maximum amplitude), and 10(-6) M ACh (177 ± 6 mg maximum amplitude) produced the highest rhythmic contractions. Both 10(-7) M PE and 10(-6) M ACh significantly increased K(+) uptake in endothelium-intact aorta versus control (121 % PE, 117 % ACh). Removal of the endothelium blunted rhythmic contractions and decreased K(+) uptake in presence of vasoactive substances (88 % PE, 81 % ACh). The inhibition of nitric oxide synthase with 10(-4) M L-NNA significantly reduced the rhythmic contractions, and it was reversed in the presence of 10(-8) M sodium nitroprusside (SNP; a nitric oxide donor). Also, we found that 10(-4) M L-NNA significantly decreased the effect of 10(-7) M PE on K(+) uptake in aortic rings (104 % PE + L-NNA vs. control). The incubation of endothelium-denuded rings with 10(-8) M SNP significantly increased the K(+) uptake (116 % SNP vs. control), similar to those observed in the presence of 10(-6) M ACh. The inhibition of protein kinase G with KT-5823 blocked SNP-mediated increase in K(+) uptake. In conclusion, these data suggest that a certain range of K(+) uptake is necessary to induce the rhythmic contractions in response to vasoactive substances.

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

Cited by 2 publications

References 38 publications

Vasodilator Effect of Cassiarin A, a Novel Antiplasmodial Alkaloid from Cassia siamea, in Rat Isolated Mesenteric Artery

Vasodilator Effect of Cassiarin A, a Novel Antiplasmodial Alkaloid from Cassia siamea, in Rat Isolated Mesenteric Artery

Effect of phenylephrine and endothelium on vasomotion in rat aorta involves potassium uptake

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