Letter by Brown and Pretorius Regarding Article, “Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients”
To the Editor:
We read with interest the article by Giannarelli et al regarding the effect of sulfaphenazole on tissue plasminogen activator release. 1 As always, the authors’ experimental design is elegant. However, it appears that an important error occurred in the calculation of net tissue plasminogen activator (t-PA) release.
The authors report on the t-PA balance. On the basis of the units and Methods, this seems to be synonymous with net release, defined in the Methods as=(Cv−Ca)×[FBF×101−hct/100], where Cv and Ca are the venous and arterial concentrations. However, the units for concentrations provided in Table 2 are also expressed as ng · min−1×100 mL forearm tissue−1. Concentrations should be expressed as ng/mL. Did the authors multiply concentration by flow in Table 2, as well? If so, the presented data may disproportionately reflect changes in flow rather than in true net release.
At the same time, the t-PA balance calculated during bradykinin seems to be 20- to 30-fold lower than that reported by others at comparable doses. The investigators gave bradykinin at a dose of 0.015 μg · 100 mL−1 · min−1. This dose would be equivalent to 225 ng/min in a man with a forearm volume of 1500 mL. Other investigators report a t-PA release of 20 to 80 ng · min−1 · 100 mL−1 at similar bradykinin doses.
The effect of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on stimulated t-PA release is a bit confusing. L-NMMA decreased t-PA release, suggesting that NO increases t-PA release. If this were the case, the NO donor nitroprusside should also stimulate t-PA release. The authors report that sodium nitroprusside does not affect t-PA release. How do the authors reconcile these discrepant findings? DeSouza and colleagues suggest that NO decreases bradykinin-stimulated t-PA release.2 Because the authors infused sodium nitroprusside concurrently with L-NMMA, is it possible that the effect attributed to L-NMMA was really an effect of nitroprusside?
Sources of Funding
This work was supported by National Institutes of Health grants HL065193, HL060906, and HL085740.
Dr Brown receives grant support from Forest Pharmaceuticals, which manufactures nebivolol.