Nitric oxide synthase-independent release of nitric oxide induced by KCl in the perfused mesenteric bed of the rat

The aim of the present study was to test whether the contractile responses elicited by KCI in the rat mesenteric bed are coupled to the release of nit ric oxide (NO). Contractions induced by 70 mM KCl were coincident with the release of NO to the perfusate. The in vitro exposure to the nitric oxide s ynthase (NOS) inhibitor L-N-omega-nitro-L-arginine methyl ester, L-NAME (1- 100 muM) potentiated the vascular responses to 70 mM KCI and, unexpectedly, increased the KCl-stimulated release of NO. Moreover, even after the chron ic treatment with L-NAME (70 mg/kg/day during 4 weeks), the KCl-induced rel ease of NO was not reduced, whereas the potentiation of contractile respons es was indeed achieved. The possibility that NOS had not been completely in hibited under our experimental conditions can be precluded because NOS acti vity was significantly inhibited after both L-NAME treatments. After the in vitro treatment with 1 to 100 muM L-NAME, the inhibition of NOS was concen tration-dependent (from 50% to 90%). With regard to the basal release of NO , the inhibition caused by L-NAME was not concentration-dependent and reach ed a maximum of 40%, suggesting that bas al NO outflow is only partially de pendent on NOS activity. An eventual enhancement of NOS activity caused by KCI was disregarded because the activity of this enzyme measured in homogen ates from mesenteric beds perfused with 70 mM KCl was significantly reduced . On the other hand, endothelium removal, employed as a negative control, a lmost abolished NOS activity, whereas the incubation with the Ca2+ ionophor e A23187, employed as a positive control, induced an increase in NOS activi ty. It is concluded that in the mesenteric arterial bed of the rat. the con tractile responses elicited by depolarization through KCl an coincident wit h a NOS-independent release of NO. This observation, which differs from the results obtained with noradrenaline, do not support the use of KCl as an a lternative contractile agent whenever the participation of NO is under stud y. (C) 2000 Elsevier Science B.V. All rights reserved.