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The impaired fibrinolytic capacity in hypertension is unaffected by acute blood pressure lowering

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Abstract

The endogenous fibrinolytic system and the ability of the endothelium to release tissue-plasminogen activator (t-PA) play a pivotal role to protect humans from atherothrombotic events. We have recently reported that the decreased capacity for t-PA release in hypertension is restored with chronic blood pressure lowering. Thus, we explored if acute blood pressure lowering has the same effect. The capacity for acute t-PA release was investigated in the perfused-forearm model during stimulation by intra-arterial substance P 8 pmol/min in hypertensive subjects. The procedure was then repeated during acute blood pressure lowering (n = 9) induced by sodium nitroprusside (SNP) infusion or during placebo infusion (n = 3). SNP lowered mean arterial pressure from 108.6 (2.6) to 83.0 (2.6) (mean and SEM) mmHg (P < 0.001). Substance P induced significant increase in t-PA release during both high- and low-pressure conditions (P < 0.01, ANOVA). Peak t-PA release rate was 199 (77) and 167 (41) (mean and SEM) ng/min/l tissue, and accumulated t-PA release was 2,395 (750) and 2,394 (473) ng, during high- and low-pressure conditions, respectively. t-PA release and hemodynamic responses were almost identical during high- and low-pressure conditions (P = ns, for all). Acute blood pressure lowering does not restore stimulated t-PA release from the endothelium in hypertensive subjects. These findings are in contrast to previously described effects of chronic blood pressure treatment. Although data need to be confirmed in a larger study, they suggest that high blood pressure decreases the cellular t-PA pool rather than interferes with release mechanisms of the protein.

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Acknowledgments

This study was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Hypertension Society, the Swedish Medical Association, the Göteborg Medical Society and King Gustaf V:s and Queen Victoria Foundation. We also want to thank laboratory technician H.K. for excellent assistance.

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The authors have no conflicts of interest to state.

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Authors and Affiliations

  1. The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Wilhelm Ridderstråle, Ott Saluveer, Maria Carlström, Sverker Jern & Thórdís J. Hrafnkelsdóttir

  2. Department of Education, Research and Quality, Landspitali University Hospital and the University of Iceland, Reykjavik, Iceland

    Thórdís J. Hrafnkelsdóttir

  3. The Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Bruna stråket 16, SE 413 45, Gothenburg, Sweden

    Ott Saluveer

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  1. Wilhelm Ridderstråle
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  2. Ott Saluveer
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  3. Maria Carlström
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  4. Sverker Jern
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  5. Thórdís J. Hrafnkelsdóttir
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Correspondence to Ott Saluveer.

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Ridderstråle, W., Saluveer, O., Carlström, M. et al. The impaired fibrinolytic capacity in hypertension is unaffected by acute blood pressure lowering. J Thromb Thrombolysis 32, 399–404 (2011). https://doi.org/10.1007/s11239-011-0595-4

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