Tonic regulation of mouse ileal ion transport by nitric oxide

The possible role of nitric oxide (NO) in the regulation of intestinal ion transport was studied in isolated sheets of mouse ileum mounted in Ussing flux chambers. The competitive NO-synthase inhibitors NG-methyl-L-arginine (L-NMA), and NG-nitro-L-arginine (L-NNA) and the effects of NO released from acidified sodium nitrite solution were evaluated in tissues pretreated with guanethidine and atropine. Serosal L-NMA or L-NNA (10-300 microM), but not NG-methyl-D-arginine (D-NMA), produced a sustained concentration-related increase in short-circuit current (Isc) and potential difference (PD) with maximal Isc increases of 50.8 +/- 8.2 and 45.5 +/- 5.8 microAmps/cm2, respectively; mucosal application of L-NMA or L-NNA produced transient increases in Isc. The A50 (and 95% CL) values for serosal L-NMA and L-NNA were 25.6 (15.7-41.9) and 8.7 (5.1-14.9) microM, respectively. L-Arginine (0.1-10 mM), but not D-arginine, produced both a concentration-related reversal of L-NMA or L-NNA-induced increases in Isc. Additionally, pretreatment with L-arginine blocked the L-NMA or L-NNA effects, suggesting a competitive interaction. L-NMA-mediated increases in Isc were unaffected by bicarbonate-free buffer, whereas replacement of chloride ions with gluconate ions almost completely attenuated the response to L-NMA. Further, the effects of L-NMA or L-NNA were blocked by tetrodotoxin or chlorisondamine, suggesting neural actions involving ganglionic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)