1 This study examined the in vitro and in vivo inhibitory effects of diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, on endothelium-dependent vasodilatations. 2 DPI (3 x 10-8-3 x 10-6 M) concentration-dependently inhibited acetylcholine (ACh)-induced relaxation in preconstricted rat thoracic aortic rings, with an IC,0 of 1.8 x 10-7 M and a maximal inhibition of nearly 100%. DPI (3 x 10-6 M) also completely inhibited the relaxation induced by the calcium ionophore, A23187 but not by sodium nitroprusside (SNP). The inhibitory effect of DPI (3 x 10-7 M) on ACh-induced relaxation was prevented by pretreatment with NADPH (5 x 10-3 M) and FAD (5 x 10-4 M) but not L-arginine (L-Arg, 2 x 10-3 M). Pretreatment with NADPH did not alter the inhibitory effect of NG-nitro-L-arginine on ACh-induced relaxation. 3 The inhibitory effect of DPI on ACh-induced relaxation in the aortae lasted >4 h after washout. In contrast to pretreatment, post-treatment (1 h later) with NADPH (5 x 10-3 M) reversed only slightly the inhibitory effect of DPI. 4 In conscious rats, DPI (10-5 mol kg-') inhibited the depressor response to i.v. infused ACh, but not SNP. However, it caused only a transient pressor response which was previously shown to be due completely to sympathetic activation. 5 Thus, DPI is an efficacious and 'irreversible' inhibitor of endothelium-dependent vasodilatation in vivo and in vitro. The mechanism of the inhibition may involve antagonism of the effects of FAD and NADPH, co-factors of NO synthase. However, unlike the N0-substituted arginine analogues (another class of NO synthase inhibitors), DPI-induced suppression of endothelium-dependent vasodilatation in vivo does not lead to a sustained rise in blood pressure.

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As currently constituted the VF-14 is probably not a useful tool in a multi-cultural population in North America. We propose revisions to the visual function assessment and suggest its inclusion in a priority scheme for penetrating keratoplasty that also includes pain and other clinical indices.

Three-dimensional ultrasound imaging provides an objective means of assessing technical outcomes from urethral bulking agent therapy not available previously. The volume and configuration information obtained allows for rational therapeutic decision-making, particularly with regard to determining the need for re-injection and recognizing the failure of an adequate therapeutic trial.

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