The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin

Modzelewska, Beata; Jóźwik, Maciej; Jóźwik, Marcin; Tylicka, Marzena; Kleszczewski, Tomasz

doi:10.1016/j.pharep.2019.05.003

Cited by 2 publications

(2 citation statements)

References 41 publications

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“…The ability of NO to relax smooth muscles is well established ( Modzelewska et al, 2019 , Modzelewska et al, 2021 ; Idrizaj et al, 2021 ). One of the mechanisms of NO smooth muscle relaxation is the activation of soluble guanylyl cyclase (sGC) ( Friebe et al, 2018 ), which is expressed in a variety of cell types and signals through cGMP on to cGMP-dependent protein kinase (PKG), phosphodiesterases or, possibly, on to cGMP-regulated channels ( Friebe and Koesling, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

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Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner

et al. 2022

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Resveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gastric tissues were obtained from patients who underwent sleeve gastrectomy for severe obesity (n = 10 aged 21–48; BMI 48.21 ± 1.14). The mechanical activity from the muscle strips was detected under isometric conditions as the response to increasing concentrations of resveratrol before and after different pharmacological treatments. Resveratrol caused an observable, dose-dependent gastric muscle relaxation. The maximal response caused by the highest concentration of resveratrol was 83.49 ± 2.85% (p < 0.0001) of the control. Preincubation with L-NNA, L-NAME, or ODQ did not prevent the resveratrol-induced relaxation. Apamin, glibenclamide, 4AP or tamoxifen, did not inhibit the relaxing effect of resveratrol, as well. In turn, blocking BKCa by TEA, iberiotoxin, or charybdotoxin resulted in inhibition of resveratrol-induced relaxation (91.08 ± 2.07, p < 0.05; 95.60 ± 1.52, p < 0.01 and 89.58 ± 1.98, p < 0.05, respectively). This study provides the first observation that the relaxant effects of resveratrol in human gastric muscle strips occur directly through BKCa channels and independently of nitric oxide signaling pathways. Furthermore, there is considerable potential for further extensive clinical studies with resveratrol as an effective new drug or health supplement to treat gastrointestinal dyspepsia and other gastric hypermotility disorders.

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Section: Discussionmentioning

confidence: 99%

“…Before each experiment, strips were activated by 80 mmol/L K + . Only strips showing a stable response to potassium were used in the experiments ( Modzelewska et al, 2019 ; Modzelewska et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner

et al. 2022

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The Mechanism Involved in the Inhibition of Resveratrol and Genistein on the Contractility of Isolated Rat Uterus Smooth Muscle

Ma,

Wang,

Zhang

et al. 2024

Nutrients

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Purpose: This study aimed to compare the effects of the phytoestrogens resveratrol (RES) and genistein (GEN) on the contractility of isolated uterine smooth muscle from rats, focusing on both spontaneous and stimulated contractions, and to investigate the underlying mechanisms. Methods: Uterine strips were suspended vertically in perfusion chambers containing Kreb’s solution, various concentrations of RES and GEN were added to the ex vivo uterine strips, and contractions were measured before and after incubation with RES or GEN. Results: (1) Both RES and GEN inhibited K+-induced contractions in a dose-dependent manner; the β/β2-adrenoceptor antagonist propranolol (PRO), ICI118551, the ATP-dependent K+ channel blocker glibenclamide (HB-419) and the NO synthase inhibitor N-nitro-L-arginine (L-NNA) diminished the inhibitory effects of RES and GEN on K+-induced contractions. (2) RES and GEN also dose-dependently inhibited PGF2α-induced uterine contractions. (3) The inhibitory effects of RES and GEN were observed in spontaneous contractile activities as well; PRO, ICI118551, HB-419 and L-NNA attenuated the inhibitory effects of RES and GEN on the spontaneous contractions of isolated uterine muscle strips. (4) RES and GEN significantly decreased the cumulative concentration response of Ca2+ and shifted the Ca2+ cumulative concentration–response curves to the right in high-K+ Ca2+-free Kreb’s solution. (5) RES and GEN markedly reduced the first phasic contraction induced by oxytocin, acetylcholine, and prostaglandin F2α but did not alter the second phasic contraction caused by CaCl2 in Ca2+-free Kreb’s solution. Conclusions: RES and GEN can directly inhibit both spontaneous and activated contractions of isolated uterine smooth muscle. The mechanisms underlying the inhibitory effects of RES and GEN likely involve β adrenergic receptor activation, reduced Ca2+ influx and release, the activation of ATP-dependent K+ channels and increased NO production.

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The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin

Cited by 2 publications

References 41 publications

Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner

Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner

The Mechanism Involved in the Inhibition of Resveratrol and Genistein on the Contractility of Isolated Rat Uterus Smooth Muscle

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