1 Our previous study demonstrated that the aortic inducible nitric oxide synthase (iNOS) expression and the plasma nitrite level in spontaneously hypertensive rats (SHR) were greater than that in age-matched Wistar-Kyoto rats (WKY). We subsequently hypothesized that the overexpression of iNOS might play an important role in the pathogenesis of hypertension in SHR. 2 In the present study, pyrrolidinedithiocarbamate (PDTC, 10 mg kg 71 day 71 , p.o., antioxidant and nuclear factor-k B inhibitor) and aminoguanidine (15 mg kg 71 day 71 , p.o., selective inhibitor of iNOS) was used to treat SHR and WKY from age of 5 weeks through 16 weeks. 3 We found that PDTC and aminoguanidine signi®cantly suppressed the development of hypertension and improved the diminished vascular responses to acetylcholine in SHR but not in WKY. Likewise, the increase of iNOS expression, nitrotyrosine immunostaining, nitric oxide production and superoxide anion formation in adult SHR were also signi®cantly suppressed by chronic treatment with PDTC and aminoguanidine. 4 In conclusion, this study demonstrated that both PDTC and aminoguanidine signi®cantly attenuated the development of hypertension in SHR. The results suggest that PDTC suppresses iNOS expression due to its anti-oxidant and/or nuclear factor-k B inhibitory properties. However, the e ect of aminoguanidine was predominantly mediated by inhibition of iNOS activity, thereby reducing peroxynitrite formation. We propose that the development of a more speci®c and potent inhibitor of iNOS might be bene®cial in preventing pathological conditions such as the essential hypertension.

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