ENDOTHELIAL CELL-ACTIVITY IN EXPERIMENTAL-HYPERTENSION - EFFECTS OF HEMODYNAMIC FACTORS

The cause of the increased endothelial cell proliferative activity found in experimental hypertension in the rat is not clear. In this experiment the part played by altered vascular hemodynamics was explored in a model in which part of the aorta was subjected to a high blood pressure and the other not. Hypertension was produced by the application of a tight ligature to the aorta between the levels of the two renal arteries, the mechanism being interference with the blood supply to the more distally placed kidney. Because the aorta is constricted, the segment above the ligature is subjected to high blood pressure and the segment below it to lowered pressure, although both segments are exposed to humoral factors such as renin and angiotensin II. Aortic endothelial cells were labeled with tritiated thymidine and cell replication and cell density studies carried out using en face monolayer preparations of endothelium. It was found that endothelial cell replication was considerably increased at 7 days following induction of hypertension in segments of aorta above the ligature but not in the segment below the ligature. The increased activity was short-lived and had returned to normal levels at 4 weeks. Cell density was increased above the ligature at both 1 and 4 weeks following induction of hypertension. The changes are consistent with the idea that the increased cell replication and consequent increased cell density above the ligature were initiated by the increased stretching of the aortic wall attending the development of hypertension.