Hyperhomocysteinemia leads to adverse cardiac remodeling in hypertensive rats.
Hyperhomocysteinemia (Hhe), linked to cardiovascular disease by epidemiological studies, may be an important factor in adverse cardiac remodeling in hypertension. Specifically, convergence of myocardial and vascular alterations promoted by Hhe and hypertension may exacerbate cardiac remodeling and myocardial dysfunction. We studied male spontaneously hypertensive rats fed one of three diets: control, intermediate Hhe inducing, or severe Hhe inducing. After 10 wk of dietary intervention, cardiac function was assessed in vitro, and cardiac and coronary arteriolar remodeling were monitored by histomorphometric, immunohistochemical, and biochemical techniques. Results showed that Hhe induced diastolic dysfunction, as characterized by the diastolic pressure-volume curve, without significant changes in baseline systolic function. Perivascular collagen levels were increased by Hhe, and there was an increase in left ventricular hydroxyproline levels. Myocyte size was not affected. Coronary arteriolar wall thickness increased with Hhe due to smooth muscle hyperplasia. Mast cells increased in parallel with Hhe and collagen accumulation. In summary, 10 wk of Hhe caused coronary arteriolar remodeling, myocardial collagen deposition, and diastolic dysfunction in hypertensive rats.
Joseph
Jacob
J
Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock 72205, USA. josephjacob@uams.edu
Washington
Abeer
A
Joseph
Lija
L
Koehler
Laura
L
Fink
Louis M
LM
Hauer-Jensen
Martin
M
Kennedy
Richard H
RH
D000818:Animals; D001160:Arterioles / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000473:pathology; D003971:Diastole; D004195:Disease Models, Animal; D005526:Food, Formulated; D006321:Heart / Q000503:physiopathology*; D006909:Hydroxyproline / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D003094:Collagen; D006909:Hydroxyproline