SUMMARY We used a cell-free, 5% albumin-containing bicarbonate saline solution to perfuse kidneys of salt-sensitive (S) and salt resistant (R) rats derived from Dahl's original strains. The animals had been maintained on diets whose salt content was either 8% ((+ )Na) or 0.4% ((-)Na). On these regimens only S( + )Na rats become hypertensive. Glomerular filtration rate (GFR), urinary sodium excretion (NaE), renal vascular resistance (RVR), and filtration fraction were measured as perfusate pressure (P) was increased in stepwise fashion from the 80-100 to the 140-160 mm Hg range. Pressure-GFR and pressure-natriuresis curves for the S( -)Na kidneys were displaced to the right of R, so that for any given value of P both GFR and NaE were significantly less for S( -)Na than for R kidneys. Kidneys from hypertensive (S( + )Na) animals had even more markedly impaired filtration and salt excretion. Although R and S( -)Na kidneys had nearly the same RVR at the lowest perfusate pressures, only the S kidney showed an autoregulatory rise in RVR as perfusate pressure was increased. 1 reported the development of two strains of rats having contrasting blood pressure responses to dietary salt. Rats of the salt-sensitive (S) strain regularly developed hypertension when maintained on a high salt diet, but remained normotensive when salt intake was low. Resistant (R) rats were normotensive regardless of their salt intake. Because of the impressive evidence that high salt intake leads to an elevated arterial blood pressure, 2 Dahl rats have been extensively studied as possiule models for human essential hypertension. The important findings to date are as follows: S rats have normal kidney function, do not show evidence of gross sodium excess even when maintained on a high salt diet, and, like hypertensive man, respond to a saline load with an "exaggerated natriuresis." 3 " 3 There is nevertheless considerable evidence that the kidney, and in particular its ability to excrete sodium, Received May 6, 1981; revision accepted December 28, 1981. is responsible for the development of salt hypertension in the Dahl rat. Dahl and coworkers 6 transplanted kidneys between S and R rats, and found that S kidneys conferred salt-sensitive hypertension on R rats, and conversely that R kidneys rendered S rats immune to the pressor effects of high salt intake. Later, Tobian et al. 7 showed that kidneys taken from normotensive S rats, when connected to the circulation of normal rats, required a higher perfusion pressure than R kidneys to excrete an equivalent amount of sodium. The kidneys showed, in other words, a rightward shift of their pressure-natriuresis curve. The S animals appear then to exemplify Guyton's hypothesis that hypertension represents an adaptive response on the part of the cardiovascular system to overcome a renal defect in salt excretion. 8Experimental findings by Girardin et al. 9 have recently cast some doubt on this satisfying and plausible hypothesis, however. Perfusing Dahl rat kidneys in an in vitro system, these worke...

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The organ clearance of insulin calculated from the rate of disappearance of immunoreactive insulin from the perfusate averages 0.76 ml.min-1.g kidneys wt-1, a value greater than the simultaneously measured glomerular filtration rate. Clearance does not fall when hormone concentration is as high as 7 X 10(-8) M (10,000 microunits/ml). Fifteen percent of the cleared insulin is excreted in the urine; the remainder is chemically modified and appears in the perfusate both as low molecular weight fragments and as high molecular weight species. In the process of clearing the hormone, kidney tissue accumulates both intact insulin and 125I-labeled insulin degradation products. the organ clearance of insulin is not curtailed when the glomerular filtration rate is sufficiently reduced (by lowering perfusate pressure) to cause urine flow to cease. Studies using hyperglycemic perfusates and kidneys taken from starving or streptozotocin-diabetic animals provided no evidence that the kidney plays a role in the regulation of plasma glucose by modulating the rate of insulin degradation.

Cation-sensitive glass electrodes have been used to measure Na and K concentrations in Necturus serum and in glomerular and proximal tubular fluid from Necturus kidney. It has been found that the ratio [Na]glomerulus/[Na]serum is 1.00 ± 0.02 and the ratio [Na]tubule/[Na]glomerulus is 0.99 ± 0.01 thus confirming previous measurements with the flame photometer which indicated that tubular Na concentration did not change as fluid moved along the proximal tubule in Necturus kidney. These results were also confirmed with cation electrodes placed in situ in the living animal. The K concentration in fluid collected from the most distal portion of the proximal tubule was found to be 1.8 ± 0.1 times more concentrated than that in the glomerulus, in agreement with a ratio of 1.6 ± 0.1 previously obtained on the basis of flame photometer measurements by Oken and Solomon.

Free water reabsorption (Twc) was measured in conscious dogs during a long-term, reasonably steady-state osmotic diuresis induced either by sodium salts or by urea. After 4 to 8 hr the original solute was partially replaced by urea or by sodium salts. Both the replacement of sodium salts by urea and the converse procedure were associated with an augmentation in Twc. During sodium diuresis Twc always fell during the first 2 or 3 hr, a change which appeared unrelated to glomerular filtration rate (GFR) or to osmolar clearance. During the course of urea diuresis Twc steadily increased and showed a positive correlation with GFR. A possible basis for such a correlation is discussed.