ENDOTHELIAL INJURY IN TRANSGENIC (MREN-2)27 HYPERTENSIVE RATS

Transgenic [(mRen-2)27] rats develop severe hypertension as the result of transfection with the mouse Ren-2 gene. This study tested the hypo thesis that hypertensive [(mRen-2)27] rats have increased endothelial dysfunction by examining the extent of vascular endothelial cell injur y and turnover within the thoracic aorta of age-matched female transge ne positive [Tg(+)] and transgene negative [Tg(-)] littermates, Transg enic hypertensive rats had arterial pressures significantly higher tha n Tg(-) animals, but no differences in heart rate or body weight. The extent of endothelial cell injury was estimated in Hautchen preparatio ns of thoracic aorta endothelium by counting cells immunostained for t he presence of cytoplasmic immunoglobulin G (IgG) at sites with or wit hout intercostal artery branches. Both Tg(+) and Tg(-) littermates had a gi eater percentage of injured endothelial cells at branch sites th an at nonbranch aorta (P < .01). However, the number of vascular endot helial cells staining positively for IgG was significantly higher in h ypertensive rats both at sites away from (P < .05) and in the immediat e vicinity of (P < .1) the orifices of intercostal arteries. En face p reparations of the thoracic aorta were also examined for cells incorpo rating 5-bromo-2'-deoxyuridine (BrdU) to estimate the percentage of en dothelial cells undergoing replication. There was no difference in end othelial cell replication at either branch or nonbranch sites between hypertensive and normotensive rats. However, the percentage of endothe lial cells undergoing replication at branch sites in both Tg(+) and Tg (-) rats was significantly greater than at nonbranch sites (P < .01). These data provide the first demonstration for the effects of high blo od pressure on the vascular endothelium of a monogenetic model of hype rtension produced by increased activity of the renin-angiotensin syste m. The divergent effects of this form of hypertension on vascular endo thelial injury and endothelial turnover suggest that the decrease in t he reparative capacity of the vascular endothelium induced by the comb ination of hypertension and associated angiotensinemia may contribute to the endothelial dysfunction accompanying vascular remodeling. (C) 1 997 American Journal of Hypertension, Ltd.