Objective To verify whether hypertension confers a hypercoagulable state in a hypertensive animal model Design The parameters of brood coagulation were compared between stroke-prone spontaneously hypertensive mts (SHR-SP) and Wistar-Kyoto (WKY) rats, Each rat group consisted of a younger subgroup at 8-12 weeks old (n = 12) and an older subgroup at 16-20 weeks old (n = 12). Methods Prothrombin time (PT), activated partial thromboplastin time (APTT), fluorogenic PT, fibrinogen, fibrin/fibrinogen degradation products (FDP), thrombin-anti-thrombin III complex (TAT), factor Xa activity, antithrombin III (AT-III), tissue factor pathway inhibitor (TFPI), protein C and C1 inhibitor were measured in both rat groups, Results There was no significant difference in FDP and TAT levels between SHR-SP and WHY rats even at 16-20 weeks when SHR-SP developed severe hypertensive vascular lesions, Contrary to expectations, fluorogenic PT and factor Xa activity were significantly lower in SHR-SP than in WHY rats. While there was no significant difference in AT-III, TFPI and protein C activities between SHR-SP and WKY rats, C1 inhibitor activity was significantly higher in SHR-SP than in WKY rats. The elevated CI inhibitor activity was inversely correlated with the reduced factor Xa activity. Gel-filtered fractionated plasma with C1 inhibitor activity had an inhibitory effect on the purified rat factor Xa, and immunodepletion of C1 inhibitor from the fractionated plasma attenuated the inhibitory effect. Conclusion These results suggest that SHR-SP get into a hypocoagulable state rather than a hypercoagulable state, and that the reduction of factor Xa activity in SHR-SP may be related to the elevation of C1 inhibitor activity, J Hypertens 2000, 18:901-909 (C) Lippincott Williams & Wilkins.
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Harvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
Guan, Jian
Clermont, Allen C.
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KalVista Pharmaceut Inc, Cambridge, MA USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
Clermont, Allen C.
Pham, Loc-Duyen
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Harvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
Pham, Loc-Duyen
Ustunkaya, Tuna
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Harvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
Ustunkaya, Tuna
Revenko, Alexey S.
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Ionis Pharmaceut Inc, Carlsbad, CA USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
Revenko, Alexey S.
MacLeod, A. Robert
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Ionis Pharmaceut Inc, Carlsbad, CA USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
MacLeod, A. Robert
Feener, Edward P.
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KalVista Pharmaceut Inc, Cambridge, MA USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA
Feener, Edward P.
Simao, Fabricio
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Harvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USAHarvard Med Sch, Joslin Diabet Ctr, Res Div, Vasc Cell Biol, One Joslin Pl, Boston, MA 02215 USA