MYOCARDIAL REMODELING IN HYPERTENSIVE REN-2 TRANSGENIC RATS

Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin. We determined the extent of left ventricul ar remodeling present in Ren-2 rats at 16 weeks of age by measuring bl ood pressure, ratio of heart weight to body weight, left ventricular w all thickness, passive (diastolic) left ventricular compliance, and le ft ventricular collagen content using hydroxyproline and collagen area fraction. Changes in perivascular fibronectin and collagen type I and III were examined with immunohistochemistry. Blood pressure values at time of death were 244+/-15 mm Hg for Ren-2 rats (mean+/-SD, n=5). Ra tios of heart weight to body weight (grams per kilogram) for Ren-2 ani mals were 4.1+/-0.2 versus 3.1+/-0.1 for controls (n=6, P<.001). Wall thickness values for control animals were 2.6+/-0.1 versus 4.1+/-0.4 m m for Ren-2 animals (P<.001). Left ventricular Ren-2 hydroxyproline me asurements were significantly decreased (3.4+/-0.2 versus 4.7+/-0.9 mg /g dry wt for controls). Significant decreases of approximately 30% we re also observed in collagen area fraction in Ren-2 rats. Immunohistoc hemical and picrosirius red staining indicated increased amounts of pe rivascular fibrosis in all Ren-2 animals (when compared with controls) with enhanced levels of perivascular fibronectin and type I and type III collagen proteins. Left ventricular compliance measurements indica ted a decrease in left ventricular volume for all left ventricular pre ssures (P=.07). In conclusion, Ren-2 animals at 16 weeks of age demons trated a substantial degree of cardiac hypertrophy that was accompanie d by perivascular but not diffuse fibrosis and a stiffened left ventri cle.