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    Efeito da n-acetilcisteína na co-transmissão purinérgica e noradrenérgica na musculatura lisa de rato
    (Universidade Federal de São Paulo (UNIFESP), 2013-10-30) Lima, Edney Posteral Silva [UNIFESP]; Jurkiewicz, Aron Jurkiewicz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    INTRODUCTION: N-acetylcysteine ​​(NAC) is a molecule provider thiol groups (SH) capable of restoring endogenous levels of cysteine ​​and reduced glutathione (GSH). Although initially introduced as a mucolytic agent in the clinic in 1960, NAC has been currently used for different clinical purposes, especially as anti-inflammatory and antioxidant agent. Recent studies have demonstrated that NAC produces hypotensive and antihypertensive effects in different models of arterial hypertension, including in humans, presumably by interfering with autonomic regulation of blood pressure. Since the action of NAC on the autonomic nervous system is still unknown, we decided to adopt a tissue rich in sympathetic nerves (vas deferens or VD) as a model for studying the sympathetic neurotransmission to investigate the possible autonomic effects of NAC. METHODS: VD of Wistar rats (16 - 24 weeks) were isolated, cleaned of surrounding tissues, placed in organ bath containing 10 ml of modified Tyrode between two parallel platinum electrodes coupled to the electrical stimulator for depolarization of sympathetic nerves from VD by electrical field stimulation (EFS, 10 Hz, 3 ms, 60 V) and induction of contractions produced by the transmitters of these nerves (ATP and NA). These neurogenic contractions were recorded by isometric transducers coupled to the analog/digital Powerlab recording system. The effects of NAC (1 to 10 mM) on these contractions were studied in the presence of opener (minoxidil or MIN, 1 mM ) and blocker (4-aminopyridine or 4-AP, 2 mM) of voltage-gated K+ channels (Kv), substrate of nitric oxide (NO) biosynthesis (L-arginine or LARG, 1 mM), inhibitor of NO biosynthesis (NG-monomethyl-L-arginine or L-NMMA, 100 µM), inhibitor of guanylate cyclase or GC (1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one or ODQ, 30 µM), non-selective (papaverine or PAP, 30 µM) and type 5-selective (sildenafil or SIL, 30 µM) inhibitors of phosphodiesterase or PDE. RESULTS: Purinergic and noradrenergic EFS-contractions of VD were respectively inhibited by antagonists of P2X-purinergic (suramin) and α1-adrenergic receptors (prazosin), confirming purinergic and noradrenergic nature of these contractions. NAC (9 and 10 mM) increased purinergic contractions (47 to 51%, n=8) and reduced noradrenergic contractions (59 to 69%, n=8) of VD. The facilitatory effect of NAC on the purinergic contractions was significantly potentiated by 4-AP (123%), L-NMMA (89%), LARG (89%) and ODQ (81%), and attenuated by PAP (19%) and MIN (66%), but not chanced by SIL. The inhibitory effect of NAC on the noradrenergic contractions was significantly potentiated by PAP (67%), SIL (88%) and MIN (80%) and attenuated by 4-AP (100%), ODQ (100%), L-NMMA (8%) and LARG (16%). CONCLUSION: The facilitation of contractions purinergic and inhibition of noradrenergic contractions by NAC, indicated that this drug significantly interferes in sympathetic co-transmission. This autonomic action of NAC involves several mechanisms, in especial opening of Kv and activation of intracellular signaling pathway mediated by NO/GC/cGMP/PKG.