A B S T R A C T Although dietary potassium deficiency (KD) results in an increase in plasma renin activity (PRA), the mechanism of this effect has not been elucidated. In the present study, isolated kidneys from normal rats or from rats made KD by diet were perfused at constant pressure (120 mm Hg) with a KrebsRinger-bicarbonate medium containing albumin. KD led to an increase in PRA (3.6 vs. 1.1 ng angiotensin I ml per h, P < 0.01), which was associated with a decrease in macula densa (MD) fluid delivery as estimated by urine flow (70 vs. 166 Iul/min per g, P < 0.005), and an increase in renal vascular resistance (RVR) as perfusion flow rate was decreased from 34 to 24 ml/min per g, P < 0.005. The increase in PRA was independent of the MD because PRA could not be suppressed when macula densa delivery was increased by perfusing KD kidneys with hypooncotic albumin. Moreover, when kidneys were made nonfiltering by perfusing with hyperoncotic albumin, PRA remained increased in KD kidneys (8.1 vs. 3.5 ng angiotensin I ml per h, P < 0.01) despite the absence of MD delivery. Because the increase in PRA in both filtering and nonfiltering KD kidneys was associated with an increase in RVR, filtering and nonfiltering kidneys were perfused with the vasodilator papaverine. Despite lower tissue K levels in KD kidneys (278 vs. 357 ,ueq/g, P < 0.01), RVR and PRA were normalized in both filtering and nonfiltering KD kidneys perfused with papaverine. In conclusion, PRA is increased in the KD isolated perfused kidney. This increase occurs independently of both the MD and of tissue K levels and is mediated by the renal vascular receptor.Portions of this work were presented at the 13th Annual