title: Underlying mechanisms involved in progesterone-induced relaxation to the pig bladder neck.
abstract: Progesterone increases bladder capacity and improves the bladder compliance by its relaxant action on the detrusor. A poor information, however, exists concerning to the role of this steroid hormone on the bladder outflow region contractility. This study investigates the progesterone-induced action on the smooth muscle tension of the pig bladder neck. To this aim, urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)]i) and tension. On phenylephrine (PhE)-precontracted strips, progesterone produced concentration-dependent relaxations only at high pharmacological concentrations. The blockade of progesterone receptors, nitric oxide (NO) synthase, guanylyl cyclase, large conductance Ca(2+)-activated K(+) (BKCa) or ATP-dependent K(+) (KATP) channels reduced the progesterone relaxations. The presence of the urothelium and the inhibition of cyclooxygenase (COX), intermediate- and small-conductance Ca(2+)-activated K(+) channels failed to modify these responses. In Ca(2+)-free potassium rich physiological saline solution, progesterone inhibited the contraction to CaCl2 and to the L-type voltage-operated Ca(2+) (VOC) channel activator BAY-K 8644. Relaxation induced by progesterone was accompanied by simultaneous decreases in smooth muscle [Ca(2+)]i. These results suggest that progesterone promotes relaxation of pig bladder neck through smooth muscle progesterone receptors via cGMP/NO pathway and involving the activation of BKCa and KATP channels and inhibition of the extracellular Ca(2+) entry through L-type VOC channels.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Vítor S
authors.initials: VS
authors.lastname: Fernandes
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Ana S F
authors.initials: AS
authors.lastname: Ribeiro
authors.affiliation: Unidad Experimental, Fundación de Investigación Biomédica, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-Sáenz
authors.affiliation: Departamento de Urología, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.
authors.forename: Igor
authors.initials: I
authors.lastname: Blaha
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Serrano-Margüello
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Martínez
authors.affiliation: Departamento de Urología, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.affiliation: Departamento de Urología, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Vázquez-Alba
authors.affiliation: Departamento de Urología, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Carballido
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: medardo@farm.ucm.es.
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000502:physiology*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D019459:Urothelium / Q000502:physiology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D016861:Cyclooxygenase Inhibitors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011810:Quinoxalines; D011980:Receptors, Progesterone; D019335:Nitroarginine; D011374:Progesterone; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D011188:Potassium; D002118:Calcium; D007213:Indomethacin
keywords: K(+) channels; Pig bladder neck; Progesterone; Smooth muscle relaxation; VOC channels