Sodium retention and hypertension after kidney transplantation in rats.

Abstract

The present study was designed to investigate the development of blood pressure and renal sodium handling in recipients of renal grafts from adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and borderline hypertensive F, hybrids bred from SHRSP and WKY rats. Unilaterally nephrectomized F, hybrids served as renal graft recipients. The second native kidney was removed 7 days after transplantation. Starting on the day of transplantation, renal graft recipients were put on a standard diet for 7 days followed by a low salt diet (0.18% salt) for 10 days and a high salt diet (1.8% salt) for another 14 days. In recipients of a renal graft from SHRSP donors, systolic blood pressure rose progressively from 140±4 mm Hg before to 190±7 mm Hg 4 weeks after transplantation. In contrast, in recipients of a renal graft from WKY rat donors, blood pressure fell during the same time from 139 ±7 mm Hg to 120 ±4 mm Hg. Blood pressure did not change significantly in recipients of a renal graft from F, hybrid donors (132±4 versus 138±7 mm Hg). With transition from a low salt to high salt diet, all rats exhibited renal sodium retention. The accumulating amount of sodium retained by the renal graft was significantly higher in recipients of an SHRSP kidney than in recipients of a WKY rat kidney at all days on the high salt diet. It was also higher in recipients of an SHRSP kidney versus recipients of an F, hybrid kidney on days 8 through 14 on the high salt diet and in recipients of an F, hybrid kidney versus recipients of a WKY rat kidney on days 1 through 5 on the high salt diet. On the low salt diet, urinary aldosterone excretion was lower in recipients of an SHRSP kidney compared with recipients of a WKY rat kidney. On the high salt diet, it was similar in both groups. Urinary corticosterone excretion was similar in both groups on the low salt diet and increased significantly on the high salt diet in recipients of an SHRSP kidney but not in recipients of a WKY rat kidney. At the end of the protocol, glomerular filtration rate, renal plasma flow, plasma sodium concentration, and fractional sodium excretion were not significantly different among groups. These results confirm our previous finding that recipients of a renal graft from SHRSP donors developed posttransplantation hypertension, whereas blood pressure actually decreased in recipients of a renal graft from WKY rat donors. In addition, the data demonstrate that posttransplantation hypertension in recipients of an SHRSP kidney is associated with increased renal sodium retention. (Hypertension 1993;21:724-730)

Transplantation of Enalapril-Treated Kidneys Confers Persistent Lowering of Arterial Pressure in SHR

“…Previously, the development of hypertension in hybrid normotensive rats transplanted with SHR kidneys was interpreted as primarily being a consequence of the hypertensive genetic background of the donor kidney. [22][23][24][25][26] The present findings demonstrate that, despite the genetic background, the kidney-specific properties that confer hypertension are modifiable by drug treatment. That is, enalapril treatment has effectively modified the age-related changes in the SHR kidney, such that after transplantation, hypertension in the untreated recipient is reversed.…”

The Kidney as a Determinant of Genetic Hypertension

“…12,28 Our own work in SHRSP yielded inconsistent results. Transplantation of a WKY kidney to bilaterally nephrectomized F1 hybrids had no effect on blood pressure in 2 studies, 31,33 whereas it decreased blood pressure compared with presurgical levels, 32 uninephrectomized F1 hybrid controls, 27 or recipients of an F1 hybrid kidney 15 in other studies. This situation was, of course, highly unsatisfactory.…”

“…Possible mechanisms include: (1) the reninangiotensin-aldosterone system, (2) renal sodium and volume handling, (3) sympathorenal interactions, and (4) (enhanced) production or inadequate excretion of a hitherto unknown hypertensinogenic substance. In several studies, 15,18,27,30,33,34 we were able to demonstrate that the renin-angiotensin-aldosterone system is not stimulated in recipients of an SHRSP or SHR kidney. Interestingly, recipients of an SHRSP kidney had a lower 24-hour urinary aldosterone secretion, 15 and recipients of an SHR kidney had lower plasma aldosterone concentrations than recipients of a kidney from normotensive donors.…”

“…In several studies, 15,18,27,30,33,34 we were able to demonstrate that the renin-angiotensin-aldosterone system is not stimulated in recipients of an SHRSP or SHR kidney. Interestingly, recipients of an SHRSP kidney had a lower 24-hour urinary aldosterone secretion, 15 and recipients of an SHR kidney had lower plasma aldosterone concentrations than recipients of a kidney from normotensive donors. 18 From these and other observations, we hypothesized that recipients of an SHRSP or SHR kidney, respectively, may have a primary defect in renal sodium handling.…”

“…In fact, when we challenged our rats with a dietary sodium load, recipients of an SHRSP kidney showed a decreased renal capacity to excrete the load. 15 The salt retention hypothesis was further supported when we found that hypertension in genetically normotensive recipients of an SHRSP kidney was associated with renal sodium retention that began when the contralateral native kidney was removed (ie, 7 days after transplantation). 14 However, if sodium retention was a causal factor for the development of hypertension in recipients of an SHRSP kidney, it should: (1) precede hypertension, (2) still be demonstrable when intestinal sodium loss is appropriately accounted for, and (3) give rise to some kind of measurable volume expansion.…”