The effects of the putatively selective inhibitor of neuronal nitric oxide synthase (nNOS) 1-(2-trifluoromethylphenyl) imidazole (TRIM) were investigated on contractility, intracellular calcium and nitrergic relaxations in the rat anococcygeus muscle. TRIM (100-1000 μM) reduced the tension of rat anococcygeus muscles when contracted with guanethidine (10 μM) and clonidine (0.1 μM). Relaxations to TRIM persisted in the presence of the non-selective NOS inhibitor l-NAME (100 μM) and the inhibitor of soluble guanylate cyclase ODQ (1 μM). TRIM also reduced tension when muscles were contracted with phenylephrine (3 μM), noradrenaline (3 μM) or high K physiological salt solution (high KPSS; 60 mM). Influx of calcium ([Ca2+]i) in response to high KPSS was significantly reduced in the presence of TRIM (1 mM). TRIM also inhibited the influx of45Ca2+induced by KPSS, but had no effect on the influx induced by phenylephrine (10 μM). TRIM (300 μM) had a modest, but significant, inhibitory effect on nitrergic relaxations that were evoked by electrical field stimulation (1-10 Hz, 15 V, 10 s trains) in muscles contracted with guanethidine and clonidine. In contrast, l-NAME (1-100 μM) inhibited these nitrergic responses with an IC50of 9.31 ± 0.87 μM (n = 4). The results suggest that the smooth muscle relaxant effect of TRIM in the rat anococcygeus muscle may affect the entry of Ca2+possibly through voltage-operated calcium channels. Furthermore, the relatively modest effect of TRIM on nitrergic responses indicates that it is not a particularly reliable inhibitor of nNOS. © 2006 Elsevier Inc. All rights reserved.
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