Benign prostatic hypertrophy has been related with glandular ischemia processes and adenosine is a potent vasodilator agent. This study investigates the mechanisms underlying the adenosine-induced vasorelaxation in pig prostatic small arteries. Adenosine receptors expression was determined by Western blot and immunohistochemistry, and rings were mounted in myographs for isometric force recording. A 2A and A 3 receptor expression was observed in the arterial wall and A 2A -immunoreactivity was identified in the adventitia-media junction and endothelium. A 1 and A 2B receptor expression was not obtained. On noradrenalineprecontracted rings, P1 receptor agonists produced concentration-dependent relaxations with the following order of potency: 5′-N-ethylcarboxamidoadenosine (NECA)= CGS21680>2-Cl-IB-MECA=2-Cl-cyclopentyladenosine= adenosine. Adenosine reuptake inhibition potentiated both NECA and adenosine relaxations. 2+ -activated-, ATP-dependent-, and voltage-gated-K + channel failed to modify these responses. These results suggest that adenosine induces endotheliumdependent relaxations in the pig prostatic arteries via A 2A purinoceptors. The adenosine vasorelaxation, which is prejunctionally modulated, is produced via NO-and COXindependent mechanisms that involve activation of IK Ca and SK Ca channels and stimulation of adenylyl cyclase. Endothelium-derived NO playing a regulatory role under conditions in which EDHF is non-functional is also suggested. Adenosine-induced vasodilatation could be useful to prevent prostatic ischemia.

These results suggest that ET-1 produces contraction via muscular ET(A) receptors coupled to extracellular Ca(2+) entry via VOC (L-type) and non-VOC channels. Intracellular Ca(2+) mobilization and a Rho/Rho-kinase pathway could also be involved in these responses. ET-1-evoked potentiation on noradrenergic contraction, and neuronal ET(A) receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated.

These results suggest that BQ3020 produces relaxation of the pig bladder neck via activation of muscle endothelin ET(B) receptors, NO/cGMP- and COX-independent-, cAMP-PKA pathway-dependent-mechanisms, and involving BK(Ca) and SK(Ca) channel activation. ET(B) receptors are also involved in the NANC inhibitory neurotransmission.