Familial hypertension, glomerular hemodynamic alterations, and dysregulation of tubulo-glomerular feedback (TGFB) have all been associated with the development of chronic renal failure. In the present study we evaluated renal and glomerular hemodynamics and TGFB responses in healthy kidney donors either with or without familial hypertension, before and after nephrectomy. Para-amino-hippurate plasma clearance (CPAH) and inulin plasma clearance (CInu) were measured in 15 kidney donors before and 1 year after nephrectomy. All subjects were normotensive and were kept in a sodium-replete state. Both clearances were measured after 40 min of constant infusion of PAH and Inu, as well as 20, 30, 50, and 60 min after the intravenous administration of acetazolamide (5 mg/kg). Glomerular hemodynamics were calculated by means of the Gomez formulae. Nephrectomy caused the expected decreases in CPAH and CInu and increase in the filtration fraction (all P < .0001). The decrease in renal resistances of the remaining kidney was greater at the afferent (-24%, P = .0075) than at the efferent arteriolar level (-17%, P < .0001). The TGFB activation was not altered by nephrectomy or by familial hypertension. Effective renal plasma flow (ERPF) decrease after TGFB activation appeared earlier than glomerular filtration rate (GFR) decrease before (P = .01), but not after, nephrectomy (P = .48). The presence of familial hypertension was associated with increased glomerular pressure (P = .0004). This study suggests that uninephrectomy in healthy human subjects causes a greater decrease in afferent arteriolar resistances, but that TGFB responses are not quantitatively altered. Familial hypertension is associated with a tendency toward higher glomerular pressures.

Genetic factors are clearly involved in the pathogenesis of essential hypertension in man. In at least three rat models of genetic hypertension it is possible to transplant the hypertension with the kidney. To see whether or not the same is true for humans, we carried out a 2-year retrospective study of 50 selected recipients of a cadaver kidney. We correlated the following factors by multivariate statistical analyses: presence or absence of hypertension in the family of donor and recipients; donor’s and recipient’s age; mean blood pressure (MBP) and antihypertensive therapy (AHT) score during dialysis; months of dialysis and body surface before transplantation; body weight, plasma creatinine, prednisone dosage and cumulative rejections with MBP and AHT score at various time intervals after transplantation. The results obtained showed that, considering the recipients coming from normotensive families, the AHT score after transplantation was significantly greater (p < 0.05 1st and p < 0.0l 2nd year) in the patients receiving a kidney removed from donors with hypertensive families than in the patients receiving a kidney removed from donors with normotensive families. This difference was not present when the recipients coming from hypertensive parents were considered. AHT score after transplantation is also correlated with AHT score on dialysis (p < 0.01 1st and 2nd year), body weight (p < 0.02 1st and p < 0.01 2nd year), cumulative rejections (p < 0.025 1st and 2nd year) and inverse MBP after dialysis (p < 0.025 2nd year).

SUMMARY The suggestion has been made that the Okamoto strain of spontaneously hypertensive rats (SHR) shares some features with a subgroup of patients with essential hypertension, called nonmodulators. One feature of nonmodulators is a renal blood flow response to angiotensin II (ANG II) that is blunted on a high salt diet; the blunted renal vascular response is corrected by converting enzyme inhibition. Renal blood flow (electromagnetic flowmeter) and pressor responses to graded ANG II doses (5-300 ng) were assessed in 24 SHR and 24 Wistar-Kyoto rats (WKY) ingesting 1.6% Na. In comparison to WKY, blood pressure was higher in SHR (155 ± 4 vs 106 ± 2 mm Hg; p<0.001), renal blood flow was lower (6.9 ± 0.5 vs 8.2 ± 0.4 ml/min/g; p<0.05), and the pressor response to ANG II was enhanced, (p<0.0005) but the renal vascular response was blunted ( p < 0.005). Captopril (1-30 mg/kg) reduced blood pressure more in SHR than in WKY but increased renal blood flow similarly in both strains. The blunted renal vascular response to ANG II in SHR was reversed by captopril, but inhibition of converting enzyme in the kidney did not parallel systemic inhibition. Maximum blockade of converting enzyme in the kidney appears to require a larger captopril dose than is required for systemic inhibition. These results suggest that the renal blood supply in SHR also shares some of the characteristics of nonmodulators and that the action of captopril on the renal blood flow probably reflects reversal of inappropriate intrarenal ANG II formation. (Hypertension 9: 591-597, 1987) KEY WORDS • sodium • angiotensin I * angiotensin II • converting enzyme inhibition renal blood flow • captopril A MONG the lines of evidence implicating the / \ kidney in the pathogenesis of hypertension a A. \ . particularly compelling observation involves the results of renal transplantation. In three unrelated strains of rats programmed genetically to develop hypertension, transplantation of a kidney from a hypertensive donor to a normotensive recipient raises the recipient's blood pressure.1 " 3 Conversely, removal of the kidneys from a hypertensive rat and replacement with a kidney from a normotensive donor prevents or

In normotensive donors with a normal compensatory response to nephrectomy, baseline renal reactivity to angiotensin II can influence renal and glomerular hemodynamics 1 year after nephrectomy.