title: Ca2+-activated K+ (KCa) channels are involved in the relaxations elicited by sildenafil in penile resistance arteries.
abstract: The aim of the present study was to evaluate the role of K+ channels in the vasorelaxant effect of the phosphodiesterase 5 inhibitor, sildenafil, in isolated horse penile resistance arteries mounted in microvascular myographs. In phenylephrine-precontracted arteries, sildenafil elicited potent relaxations which were markedly reduced by raising extracellular K+, by the non-selective blocker of Ca2+-activated K+ channels (KCa), tetraethylammonium and by the blocker of large- and intermediate-conductance KCa channels, charybdotoxin. Sildenafil relaxant responses were also reduced by the selective inhibitor of large conductance KCa (BK(Ca)) channels iberiotoxin, but not by the blocker of small conductance KCa channels apamin. The inhibitor of the cGMP-dependent protein kinase (PKG), Rp-8-Br-PET-cGMPS, reduced the relaxations elicited by sildenafil but combined treatment with iberiotoxin and Rp-8-Br-PET-cGMPS did not further inhibit these relaxations, compared to the effect of either blocker alone. Iberiotoxin also shifted to the right the relaxations elicited by both the NO donor, S-nitrosoacetyl-D,L-penicillamine (SNAP) and the adenylate cyclase activator forskolin; treatment with both iberiotoxin and Rp-8-Br-PET-cGMPS did cause an additional inhibition. The present results demonstrate that the relaxant effect of sildenafil and NO in penile resistance arteries is due in part to activation of BK(Ca) channels through a PKG-dependent mechanism.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. dprieto@farm.ucm.es
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.forename: Nuria
authors.initials: N
authors.lastname: Villalba
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006736:Horses; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010413:Penis / Q000098:blood supply*; D010455:Peptides / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D011687:Purines; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones; D019789:Tetraethylammonium / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D020030:Nitric Oxide Donors; D010455:Peptides; D010879:Piperazines; D024681:Potassium Channels, Calcium-Activated; D011687:Purines; D013450:Sulfones; D013873:Thionucleotides; D014665:Vasodilator Agents; D018999:Charybdotoxin; C098740:8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate; D005576:Colforsin; D019789:Tetraethylammonium; C064719:iberiotoxin; D026423:S-Nitroso-N-Acetylpenicillamine; D000068677:Sildenafil Citrate; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D011188:Potassium