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Nitric oxide (NO) slightly inhibits the calcium current (ICa,L) of L-type calcium channel (LTCC).The enhanced ICa,L induced by isoproterenol (ISO) in cardiomyocytes was decreased in nNOS knockout mice or 4-week of tail-suspended (SUS) rats.The underlying mechanism is not resolved.Therefore, the purpose of this study was to investigate the effect of nNOS-derived NO on LTCC gating property of cardiomyocytes during ISO treatment.In the present study, expression and activity of nNOS was decreased in the myocardium of SUS rats.Superoxide anion radical production increased in cardiomyocytes of the SUS group after ISO stimulation.S-nitrosylation of LTCC 1 C subunit significantly decreased in the SUS group.ISO-induced enhancement of ICa, L in the SUS group was less than that in the CON group.The maximal ICa, L decreased to about 80% and 60% initial value at the 50th minute of ISO treatment in the CON and SUS group, respectively.Specific inhibitor NAAN of nNOS reduced the maximal ICa,L to 50% initial value in the CON group, in contrast NO donor SNAP kept the maximal ICa,L in the SUS group to the similar extent of the CON group after 50 min of ISO treatment.The steady-state activation, inactivation and recovery curves of LTCC were changed in the SUS group after ISO treatment.In conclusion, nNOS-derived NO-induced S-nitrosylation of LTCC 1C subunit slightly inhibits ICa,L.However, the inhibitory effect on ICa,L may competitively prevent oxidation of LTCC from reactive oxygen species and protects the gating property of LTCC during long-term of ISO stimulation.