How Selective Is 7-Nitroindazole, An Inhibitor of Neuronal Nitric Oxide Synthase?

To the Editor: We read with interest the article by Kahn et al. [1] containing data on the effect of 7-nitroindazole (7NI), a purportedly selective inhibitor for neuronal nitric oxide synthase (nNOS), on arterial blood pressure (ABP). The proposal that 7NI does not affect endothelial NOS was based on the reported inability of 7NI to affect ABP and cholinergic vasodilation in vivo [2,3]. However, effects of 7NI on cholinergic vasodilation [4,5] and ABP [4,6,7] have been demonstrated. Moreover, we found that the pressor effect of 7NI is conserved in rats with pithed spinal cords and therefore is not mediated by the central nervous system. The failure of others to detect these effects may be explained by the small sample size [8,9] or by the use of anesthesia (halothane, barbiturates) that attenuates endothelial NO-dependent vasoresponsiveness and hypertension [10-12]. Unusually high ABP variability (intergroup differences