Nitric oxide synthase-independent release of nitric oxide induced by KCl in the perfused mesenteric bed of the rat
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Date
2000
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Abstract
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 nitric 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 synthase (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 chronic treatment with L-NAME (70 mg/kg/day during 4 weeks), the KCl-induced release of NO was not reduced, whereas the potentiation of contractile responses was indeed achieved. The possibility that NOS had not been completely inhibited under our experimental conditions can be precluded because NOS activity 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 concentration-dependent (from 50% to 90%). With regard to the basal release of NO, the inhibition caused by L-NAME was not concentration-dependent and reached a maximum of 40%, suggesting that bas al NO outflow is only partially dependent on NOS activity. An eventual enhancement of NOS activity caused by KCI was disregarded because the activity of this enzyme measured in homogenates from mesenteric beds perfused with 70 mM KCl was significantly reduced. On the other hand, endothelium removal, employed as a negative control, almost abolished NOS activity, whereas the incubation with the Ca2+ ionophore A23187, employed as a positive control, induced an increase in NOS activity. It is concluded that in the mesenteric arterial bed of the rat. the contractile responses elicited by depolarization through KCl an coincident with 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 alternative contractile agent whenever the participation of NO is under study. (C) 2000 Elsevier Science B.V. All rights reserved.
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nitric oxide (NO), mesenteric bed, N-omega-nitro-L-arginine methyl ester, depolarization, KCl, nitric oxide (NO) synthase