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.