title: Role of both actin-myosin cross bridges and NO-cGMP pathway modulators in the contraction and relaxation of human placental stem villi.
abstract: BACKGROUND
  Human placental stem villi (PSV) present contractile properties. We studied the role of actin-myosin cross bridges (CBs) and the effects of NO-cGMP pathway modulators in the PSV contraction and relaxation.
  
  
  METHODS
  In vitro contractile properties were investigated in 71 PSV from term human placentas studied according to their long axis. Contraction was induced by both KCl and electrical tetanic stimulation. Relaxation was induced by inhibiting the CB cycle with either 2,3-butanedione monoxime (BDM) or blebbistatin (BLE) and by activating the NO-cGMP pathway with isosorbide dinitrate (ISDN), sildenafil (SIL) or ISDN + SIL.
  
  
  RESULTS
  PSV tension slowly increased by 140% of the basal tone after KCl exposure and by 85% after tetanus. The addition of BDM, BLE, ISDN, SIL and ISDN + SIL induced a relaxation of PSV, the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). These relaxation kinetics were particularly slow. Other relaxation parametres, i.e., maximum lengthening, -peak dT/dt, and resting tension, did not differ between these 5 subgroups.
  
  
  CONCLUSIONS
  Isolated human PSV were able to contract after both KCl exposure and tetanus. This increase in contractility was reversed by inhibiting the CB cycle with BDM or BLE and by stimulating the NO-cGMP pathway with ISDN or SIL. The association ISDN + SIL did not potentiate the relaxing processes.
authors.affiliation: Centre de Recherche Clinique, Centre Hospitalier Régional de Meaux, France; UMR-S 1139 INSERM Université Descartes Paris 5, Sorbonne Paris Cité, France.
authors.forename: E
authors.initials: E
authors.lastname: Lecarpentier
authors.forename: V
authors.initials: V
authors.lastname: Claes
authors.forename: O
authors.initials: O
authors.lastname: Timbely
authors.forename: J-L
authors.initials: JL
authors.lastname: Hébert
authors.forename: A
authors.initials: A
authors.lastname: Arsalane
authors.forename: A
authors.initials: A
authors.lastname: Moumen
authors.forename: C
authors.initials: C
authors.lastname: Guerin
authors.forename: M
authors.initials: M
authors.lastname: Guizard
authors.forename: F
authors.initials: F
authors.lastname: Michel
authors.forename: Y
authors.initials: Y
authors.lastname: Lecarpentier
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D002824:Chorionic Villi / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D007700:Kinetics; D009218:Myosins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D018583:Pliability / Q000187:drug effects; D011189:Potassium Chloride / Q000378:metabolism; D011247:Pregnancy; D020836:Protein Structure, Quaternary; D011687:Purines / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D047929:Term Birth
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D020030:Nitric Oxide Donors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; C004717:diacetylmonoxime; C472645:blebbistatin; D009569:Nitric Oxide; D011189:Potassium Chloride; D000068677:Sildenafil Citrate; D009218:Myosins; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate; D003931:Diacetyl
keywords: 2,3-Butanedione monoxime; Actin myosin crossbridges; Blebbistatin; Human placenta; Isosorbide dinitrate; NO-cGMP pathway; Sildenafil