Caracterização farmacologica do relaxamento da musculatura lisa do corpo cavernoso humano isolado induzido por cininas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

Objective: To caracterize the kinin receptor subtype involved in the relaxation of human isolated corpus cavernosum (HCC) induced by bradykinin (BK). Lysbradykinin (Lys-BK), Met-Lys-bradykinin (Met-Lys-BK) and des-Arg9-bradykinin (des-Arg9-BK), and to investigate whether the kinin-induced relaxation of HCC results from the stimulation of nonadrenergic, noncholinergic (NANC) neurons supplying the cavernosal tissue. Materiais and Methods: Excised HCC tissues were immediately placed in Krebs solution and kept at 4°C until use (never >24 hours after removal). HCC was cut in strips of - 2 centimetres, supended in a cascade system and superfused with oxygenated and warmed Krebs solution at 5 mUminute. After equilibration for - 90 minutes , noradrenaline (3IJmoI/L)was infused to induce a submaximal contraction of the HCC strips. The release of cyclo-oxygenase products was prevented by infusing indomethacin (6IJmoI/L). HCC strips were calibrated by injecting a single bolus of the nitrovasodilator glyceryl trinitrate (GTN) and the sensitivity of the tissues adjusted electronically to be similar.The agonists (kinins, histamine and acetylcholine)were injected as a single bolus (up to 1001JL)and the relaxation of HCC expressed as a percentage of the submaximal relaxation induced by GTN. Resul1s: Bradykinin, Lys-BK and Met-Lys-BK significantly relaxed the HCC tissues; on a molar basis, there was no statistical difference among the degrees of relaxation induced by these peptides. The B1kinin receptor agonist des-Arg9-bradykinin had no effect on the HCC. The infusion of the B2 kinin receptor antagonist Hoe 140 (50nmoI/L) virtually abolished the relaxation induced by BK, Lys-BK and Met-Lys-BK without affecting those induced by acetylcholine and histamine. The infusion of the nitric oxide synthase inhibitor NW-nitro-L-argininemethyl ester increased the tone or the HCC tissues and significantly reduced (p <0.01) the relaxation induced by BK (74%), Lys-BK (90%), Met-Lys-BK (87%) and acetylcholine (89%) without affecting those induced by GTN. The subsequente infusion of L-arginine (300 J,JmoI/L) partially reversed the increased tone and significantly (P <0.01) restored the relaxationinduced by Bk, Lys-BKand Met-Lys-BK.The resultswere similar with the novel guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3,-alquinoxalin-1-one] which reduced by >95% (p >0.01) the relaxation induced by BK, Lys-BK, Met- Lys-BK, acetylcholine and GTN. The infusion of the sodium-channel bolcker tetrodotoxin had no signficant effect on the BK-, GTN- and acetylcholine-induced relaxation of HCC. Conclusion: This study clearly showed the existence of functional B2kinin receptors in human erectile tissues that when activated lead to the release of NO and hence relaxation of the HCC tissues. As tetrodotoxin failed to affect the kinin-induced relaxation of HCC strips, it is likely that these peptides release NO frem the endotheliumof sinuoidal capillaries rather than from neuronal sources supplying the cavernosal tissue. Although tissue kallikreins and their components have been found in the male reproductive system, the physiopathological importance of these findings has yet to be elucidated

ASSUNTO(S)

cininas penis - musculos penis - ereção

ACESSO AO ARTIGO

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