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...

Isolated rat kidneys respond to elevations of perfusion pressure with an increase in glomerular filtration rate (GFR), filtration fraction (FF), and sodium excretion (UNaV) and a fall in fractional sodium reabsorption (FRNa). Significant linear correlations exist between each of these dependent variables and the renal artery pressure (P). In control kidneys, pressure natriuresis is seen to result both from an increase in filtered sodium load and a decrease in FRNa. In kidneys treated with indomethacin in doses which curtail the release into the perfusate of prostaglandin E2 (PGE2) and the prostacyclin metabolite, 6-keto-PGF1 alpha, the regression lines relating GFR, FF, and UNaV to P are shifted to the right. Thus, prostaglandin-inhibited kidneys require higher pressures than control kidneys to maintain comparable rates of filtration and sodium excretion. Total renal vascular resistance (RVR) is also higher in inhibited kidneys. These findings suggest that in the isolated perfused rat kidney, prostaglandins promote pressure natriuresis by maintaining afferent arteriolar dilation. Their inhibition leads to afferent constriction, which raises RVR, lowers FF and GFR, and reduces sodium excretion.

Total mineralocorticoid activity in human serum was assessed by the rat renal slice receptor assay (RRA). RRA values were compared to RIA-derived aldosterone (aldo) equivalents. Our data demonstrate that in normal subjects, mineralocorticoid receptor-binding steroids can be almost totally accounted for by immunoreactive deoxycorticosterone, corticosterone, cortisol, and aldo (RRA, 4.73 +/- 1.34 ng/ml aldo; RIA, 3.91 +/- 1.52 ng/ml aldo equivalents), while in 8 patients with dexamethasone-suppressible hyperaldosteronism (DSH), RRA values were greater than RIA values in the basal state (RRA, 7.57 +/- 0.75; RIA, 3.24 +/- 0.34; P less than 0.01). DSH patients had a RRA to RIA ratio after ACTH stimulation similar to the ratio in these patients in the basal state (basal, 2.34; ACTH-stimulated, 2.04). During dexamethasone treatment, RRA values fell markedly (1.82 +/- 0.26). Thus, total mineralocorticoid activity, as measured by RRA in DSH patients, was greater than RIA-measurable deoxycorticosterone, corticosterone, cortisol, and aldo, indicating the presence of an unidentified steroid which is dexamethasone suppressible and ACTH stimulable.