Letter by Brown and Pretorius Regarding Article, “Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients”

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HomeCirculationVol. 120, No. 19Letter by Brown and Pretorius Regarding Article, “Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Brown and Pretorius Regarding Article, “Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients” Nancy J. Brown Mias Pretorius Nancy J. BrownNancy J. Brown Vanderbilt University School of Medicine, Division of Clinical Pharmacology, Department of Medicine, Nashville, TN Search for more papers by this author Mias PretoriusMias Pretorius Vanderbilt University School of Medicine, Department of Anesthesia, Nashville, TN Search for more papers by this author Originally published10 Nov 2009https://doi.org/10.1161/CIRCULATIONAHA.109.874743Circulation. 2009;120:e159To 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 FundingThis work was supported by National Institutes of Health grants HL065193, HL060906, and HL085740.DisclosuresDr Brown receives grant support from Forest Pharmaceuticals, which manufactures nebivolol. References 1 Giannarelli C, Virdis A, De Negri F, De NF, Magagna A, Duranti E, Salvetti A, Taddei S. Effect of sulfaphenazole on tissue plasminogen activator release in normotensive subjects and hypertensive patients. Circulation. 2009; 119: 1625–1633.LinkGoogle Scholar2 Smith DT, Hoetzer GL, Greiner JJ, Stauffer BL, DeSouza CA. Endothelial release of tissue-type plasminogen activator in the human forearm: role of nitric oxide. J Cardiovasc Pharmacol. 2003; 42: 311–314.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 10, 2009Vol 120, Issue 19 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.109.874743PMID: 19901200 Originally publishedNovember 10, 2009 PDF download Advertisement SubjectsClinical StudiesEndothelium/Vascular Type/Nitric OxideThrombosis