Does hypertension confer a hypercoagulable state in stroke-prone spontaneously hypertensive rats?
OBJECTIVE
To verify whether hypertension confers a hypercoagulable state in a hypertensive animal model.


METHODS
The parameters of blood coagulation were compared between stroke-prone spontaneously hypertensive rats (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, anti-thrombin 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 WKY 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 WKY 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 C1 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


CONCLUSIONS
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.
Research Institute and National Cardiovascular Center, Suita, Osaka. tabumiya@ri.ncvc.go.jp
T
T
Abumiya
T
T
Sakata
K
K
Enjyoji
H
H
Kato
J
J
Kawai
T
T
Suzuki
J
J
Masuda
T
T
Sasaguri
J
J
Ogata
D000818:Animals; D001772:Blood Cell Count; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000150:complications / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D029968:Escherichia coli Proteins; D015951:Factor Xa / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D010314:Partial Thromboplastin Time; D011486:Protein C / Q000378:metabolism; D011517:Prothrombin Time; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000473:pathology
D002352:Carrier Proteins; D003174:Complement C1 Inactivator Proteins; D029968:Escherichia coli Proteins; D005338:Fibrin Fibrinogen Degradation Products; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor; C408585:twin-arginine translocase complex, E coli; D005340:Fibrinogen; D015951:Factor Xa