METHODS

In this experiment, we would have preferred to test perfusion pressures both higher and lower than normal. However, when a clip is allowed partially to constrict one renal artery in a rat for 24 hours, no increase in juxtaglomerular granulation occurs in the clipped kidney at the end of the 24 hours, even though such an increase usually occurs after a few weeks. This experiment sug-gested that lowering the perfusion pressurewould not produce any detectable changes within the space of a four hour perfusion experiment. Hence, we were prompted to compare perfusion pressures slightly below normal with distinctly high perfusion pressures. The design of our perfusion apparatus is illustrated diagrammatically in Figure 1. A normal male Wistar rat (A) provided oxygenated and" biochemically supported" blood through its carotid artery (B) to some Tygon tubing (C) which ran through a Sigmamotor® pump (D). The pump could be regulated to increase or decrease the pressure of blood flowing into the Tygon tubing distal to it, which was connected to the renal artery ofan isolated normal rat kidney (E). The isolated kidney was always obtained from a normal male Wistar rat and was removed in such a way that it never had more than 15 seconds of ischemia during the" hooking-up" period before being placed in thewarm chamber (F). This warm chamber contained a space which just fitted the kidney and served* This investigation was supported by a grant from the American Heart Association and by Grant No. H 2008 from the National Heart Institute, United States Public Health Service. to maintain it at body temperature. The isolated kidney was wrapped in a Saran® plastic film to reduce evaporation and to prevent any contact with the potentially toxic heavy metals of the warm chamber. A side arm in the tubing between the pump and the kidney was connected to a mercury manometer (G) which was monitored con-tinuously to determine whether the pump required any adjustment to maintain a given constant perfusion pressure. The blood leaving the isolated kidney via the renal vein went through polyethylene tubing to a miniature Murphy drip apparatus (H), which provided an esti-mate of the magnitude of flow. From there, it returned through some more polyethylene tubing to the jugular vein of the original rat (I). Heparin was added to the circulating blood to prevent clotting. The" blood donor" rat (A) was anesthetized with Nembutal®. His trachea was cannulated to prevent any airway obstruction. The perfusions lasted from one to four hours. Sixteen kidneys were perfused at about 85 mm. Hg, a level on the low side of normal but one at which renal autoregulation is considered to be intact (2). These perfusions at a relatively low pressure were com-pared with 21 other experiments where the perfusion pressure varied between 167 and 192 mm. Hg. When the isolated kidney intended for perfusion was first obtained, the opposite kidney was also removed and subsequently sectioned. The juxtaglomerular indices in both kidneys were estimated using the Hartroft method (3) as employed in our laboratory (1). Six different sections from each kidney were counted and then aver-aged, thereby increasing our precision two and one-half