title: Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries.
abstract: Benign prostatic hypertrophy has been known to be related with glandular ischemia processes, and nitric oxide (NO) is a potent vasodilator agent. Therefore, the current study investigates the mechanisms underlying the NO-induced vasorelaxation in pig prostatic small arteries. In microvascular myographs, relaxation to electrical field stimulation (EFS), or to exogenous (S)-nitroso-N-acetylpenicillamine (SNAP) and acetylcholine (ACh), was observed on noradrenaline-precontracted prostatic small arterial rings under non-adrenergic and non-cholinergic (NANC) conditions. EFS (1-16 Hz) and exogenous SNAP (0.1-30 μM) evoked frequency- and concentration-dependent relaxation, respectively. Tetrodotoxin, a neuronal voltage-gated Na(+) channel blocker, abolished the EFS-evoked relaxation. ACh (1 nM-10 μM) induced concentration-dependent relaxation, which was reduced by the NO synthase inhibitor N(G)-nitro-L: -arginine (L: -NOARG). L: -NOARG also reduced the EFS-elicited relaxation but failed to modify the response to SNAP. 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin (IbTX), blockers of soluble guanylyl cyclase and large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, respectively, reduced EFS-, SNAP-, and ACh-induced relaxation. The combination of ODQ with IbTX did not produce further inhibition of the responses to either SNAP or ACh, compared with ODQ alone. Blockade of cyclooxygenases and intermediate and small conductance Ca(2+)-activated, ATP-dependent, and voltage-gated K(+) channels did not change the EFS and SNAP responses. In conclusion, our results suggest that NO and non-NO non-prostanoid factor(s) derived from NANC nerves are involved in the vasodilatation of pig prostatic small arteries. NO produces relaxation through soluble guanylyl cyclase activation-dependent BK(Ca) channel opening and through guanylyl cyclase-independent mechanisms. The vasodilatation elicited by NO could be useful to prevent prostatic ischemia.
authors: Departamento de Fisiología, Universidad Complutense de Madrid, Spain.
authors: Vítor S
authors: VS
authors: Fernandes
authors: Ana
authors: A
authors: Martínez-Sáenz
authors: Paz
authors: P
authors: Recio
authors: Ana S F
authors: AS
authors: Ribeiro
authors: Ana
authors: A
authors: Sánchez
authors: María Pilar
authors: MP
authors: Martínez
authors: Ana Cristina
authors: AC
authors: Martínez
authors: Albino
authors: A
authors: García-Sacristán
authors: Luis M
authors: LM
authors: Orensanz
authors: Dolores
authors: D
authors: Prieto
authors: Medardo
authors: M
authors: Hernández
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011467:Prostate / Q000098:blood supply* / Q000187:drug effects; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine