Development of hyperfibrinogenemia in spontaneously hypertensive and hyperlipidemic rats: a potentially useful animal model as a complication of hypertension and hyperlipidemia.
According to current concepts, hypertension and hyperlipidemia cause vascular damage that leads to a hypercoagulative state. In this study, we investigated whether spontaneously hypertensive and hyperlipidemic rats (SHHR) can be a useful experimental model for complications in combined hypertension and hyperlipidemia, by comparing coagulative and fibrinolytic activities in SHHR with those in spontaneously hypertensive rats (SHR) and spontaneously hyperlipidemic rats (HLR). We measured coagulation and fibrinolysis markers in plasma and levels of fibrinogen and prothrombin mRNA in livers of eight-month-old male Wistar Kyoto rats (WKY), Sprague-Dawley rats (SD), SHR, HLR and SHHR. The plasma levels of fibrinogen in SHR, HLR and SHHR were significantly higher than those in WKY and SD, and were highest in SHHR. Higher plasma levels of antithrombin III and plasminogen were detected in increasing order in SHR, HLR and SHHR as compared to those in WKY and SD. Hepatic mRNA expressions of fibrinogen chains and prothrombin were enhanced in SHR, HLR and SHHR, resulting in increased plasma fibrinogen levels in SHHR. These results suggest that hypertension and hyperlipidemia can each cause hypercoagulation, with hyperlipidemia being a stronger factor than hypertension. Since a greater hypercoagulative state is a complication of combined hypertension and hyperlipidemia, the SHHR model is a good system for studying the early stage of atherosclerosis ensuing from hyperfibrinogenemia.
Gomibuchi
Hiroshi
H
Department of Pharmacology, Showa University School of Medicine, Tokyo 142-8555, Japan.
Okazaki
Masako
M
Iwai
Shinichi
S
Kumai
Toshio
T
Kobayashi
Shinichi
S
Oguchi
Katsuji
K
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications*; D006973:Hypertension / Q000097:blood / Q000150:complications*; D008297:Male; D010958:Plasminogen / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D019851:Thrombophilia / Q000209:etiology*
D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D010958:Plasminogen