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

Nutrients. 2024 Oct 9;16(19):3417. doi: 10.3390/nu16193417.

Abstract

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.

Keywords: Ca2+ influx and release; genistein; resveratrol; smooth muscle; uterine movement.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Dinoprost / analogs & derivatives
  • Dinoprost / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Genistein* / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Phytoestrogens / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol* / pharmacology
  • Uterine Contraction* / drug effects
  • Uterus / drug effects

Substances

  • Genistein
  • Resveratrol
  • Phytoestrogens
  • Dinoprost
  • Calcium