A new model of isolated systolic hypertension induced by chronic warfarin and vitamin K1 treatment.
BACKGROUND
Isolated systolic hypertension is the predominant form of hypertension in the elderly population. Reduction of arterial compliance appears to contribute to the elevation of pulse pressure (PP) and among potential mechanisms, gradual vascular calcification, fragmentation of elastic lamellae, and augmentation of rigid component like collagen could contribute to increase aortic stiffening. Few experimental models of the disease are currently available.


METHODS
To induce large artery calcification, rats were treated with warfarin and vitamin K(1) (WK) for 4 and 8 weeks, to inhibit the maturation of matrix Gla protein. The impact of chronic PP elevation was determined on large artery and cardiac remodeling and on aortic endothelial function.


RESULTS
The WK treatment led to aortic medial calcification and a proportional elevation of PP, attributable mainly to a selective elevation of systolic blood pressure. The chronic treatment also increased collagen, whereas elastin decreased in the aorta. Pulse wave velocity, an index of aortic stiffening, increased in rats treated with WK. However, indices of left ventricular and aortic hypertrophy and remodeling remained normal. In addition, the WK treatment did not modify the vasoconstriction to norepinephrine and endothelin-1, and the vasodilatory response to acetylcholine and sodium nitroprusside.


CONCLUSIONS
Chronic treatment with WK represents a new model of isolated systolic hypertension with several characteristics of the human disease. The relative ease to induce calcification in this model may help to foster more fundamental research, which is lacking in this type of hypertension.
Essalihi
Rachida
R
Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada.
Dao
Huy Hao
HH
Yamaguchi
Nobuharu
N
Moreau
Pierre
P
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000139:chemically induced; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004549:Elastin / Q000378:metabolism; D006439:Hemodynamics; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013599:Systole; D014652:Vascular Diseases / Q000139:chemically induced; D014666:Vasomotor System / Q000503:physiopathology; D010837:Vitamin K 1 / Q000008:administration & dosage*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D014859:Warfarin; D010837:Vitamin K 1; D003094:Collagen; D004549:Elastin; D012083:Renin; D002118:Calcium