Clip-ablation. A model of experimental hypertension in the rat

A model of experimental hypertension has been developed in which the features of the two kidney-one clip and renal ablation models are combined in a single rat. It has been designated the clip-ablation model. It is produced by the placement of a silver clip with an opening of 0.13 mm on a branch of the left renal artery supplying one-third of that kidney, followed by right nephrectomy. In this way the effects of renin-dependent hypertension may be studied in glomeruli which are undergoing compensatory changes in response to reduction in renal mass. Clip-ablation rats were compared to rats with 1 1/3 reduction of renal mass at various intervals up to 28 days after operation. Systolic blood pressure rose with increasing time after operation in both groups with the increase being greater in the clip-ablation rats (177 +/- 10 mm Hg) as compared to the ablation rats (153 +/- 6 mm Hg) at 28 days. Plasma renin activity was increased slightly at 3 days in the ablation rats but had returned to normal levels by 28 days. By contrast, the plasma renin activity rose throughout the experimental period in the clip-ablation rats and attained a level of 32.3 +/- 8.0 ng/ml/hour by 28 days. Urine protein was significantly higher than normal only in the 28-day clip ablation rats (71.2 +/- 23.9 mg/24 hour). Glomerular damage index (GDI), a measure of glomerular injury, increased with longer intervals from operation in both experimental groups, paralleling the rise in systolic blood pressure. Beginning on day 14 and onward the GDI was always numerically higher in the clip-ablation rats than in the ablation rats. Stepwise multiple regression analysis indicated that the strongest predictor of GDI was the change in blood pressure. Plasma renin activity had an additional independent effect on GDI in the clip-ablation rats. The finding of more glomerular damage in the clip-ablation rats than in those with simple removal of comparable amounts of renal tissue is in contrast to the lesser amount of damage found in the two kidney-one clip model when compared with the model of removal of renal substance. It is likely that the compensatory hemodynamic changes in response to reduction in renal mass in the glomeruli of clip-ablation rats make them more vulnerable to injury when exposed to a renin-angiotensin induced hypertension.