Objective To study the effect and its mechanism of antihypertensive of combination of nifedipine and histone deacetylase 8 inhibitor PCI34051 on hypertension rats induced by -nitro-arginine. Methods Rats for hypertension were induced by injection of L-nitro-arginine, which were treated by nifedipine (0.5 mg /Kg), histone deacetylases inhibitor PCI34051 (07 mg /Kg), and nifedipine (0.5 mg /Kg) combined with the PCI-34051 (0.7 mg /Kg). The blood pressure and heart rate were measured by tailcuff, and the contents of serum endothelin (ET1), nitric oxide (NO), renin, angiotensin Ⅱ (Ang II) and aldosterone (ALD) were detected by enzymelinked immunosorbent assay (ELISA).〖WTHZ〗Results Compared with mode group, nifedipine, PCI-34051 and combination groups had antihypertensive effect. The contents of ET-1, AngⅡ, ALD were decreased and NO was enhanced (P＜0.05) after 24 h of single administration or successive administration for 4 weeks. Among the three groups, the antihypertensive effect of combination group was significantly stronger than that of nifedipine or PCI-34051 alone (P＜0.05). In addition, compared with the normal group, nifedipine group accelerated the heart rate of experimental rats (P＜0.05), while there was no significant effect in PCI-34051 and combination groups (P＞0.05). The nifedipine group had no effect on renin (P＞0.05), but which was decreased in PCI34051 and combination groups (P＜0.05).Conclusion Nifedipine combined with histone deacetylase 8 inhibitor PCI34051 has a synergistic antihypertensive effect on rats induced by Lnitroarginine. The mechanism is related to the improvement in dysfunction of blood vessel endothelium by lowering serum ET-1, elevating serum NO contents, and the inhibition of RAAS system activity by reducing serum renin, AngⅡ and ALD contents.