Salt-sensitivity of blood pressure and decreased 11beta-hydroxysteroid dehydrogenase type 2 activity after renal transplantation.
BACKGROUND
High blood pressure (BP) predicts a poor long-term kidney graft outcome. The mechanisms for hypertension in renal graft recipients are only partly understood. There is evidence that BP is salt dependent in renal transplant recipients. We hypothesize that renal transplantation induces salt sensitivity by decreasing 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) activity.


METHODS
A syngenic uninephrectomized rat transplantation model (Lewis to Lewis) (n=7) was used to demonstrate salt sensitivity after transplantation. Sham-operated (n=5) and denervated rats (n=5) were used as controls. In all rats, BP was measured continuously by telemetry 24 hr a day, whereas the rats were set successively on a normal- (0.45% NaCl), high- (8% NaCl), low- (0.1% NaCl), and, again, normal-salt (0.45% NaCl) diet during a 6-day period to assess salt-related changes in mean arterial pressure (MAP). 11betaHSD2 activity was assessed by determining the ratio of corticosterone to dehydrocorticosterone metabolites (THB+5alphaTHB)/THA in urine.


RESULTS
After uninephrectomy and implantation of the telemetry device, MAP was comparable in rats assigned to undergo sham operation (100+/-3 mmHg), denervation (105+/-5 mmHg), or transplantation (102+/-6 mmHg). When animals were switched from the normal- to high-salt diet, the increase in MAP was more pronounced in the transplanted group (13.9+/-5.1 mmHg) than in those undergoing sham operation (5.1+/-1.7 mmHg, P<0.004) or denervation (7.1+/-1.8 mmHg, P<0.021). Urinary (THB+5alphaTHB)/THA increased more than 2-fold in the transplanted rats but remained stable in the sham-operated and denervated animals (P<0.0001), indicating reduced activity of 11betaHSD2.


CONCLUSIONS
Syngenic renal transplantation causes salt sensitivity with increased BP associated with a reduced activity of 11betaHSD2.
Schumacher
Martin
M
Division of Nephrology and Hypertension and Institute of Physiology, University of Fribourg, Switzerland.
Frey
Felix J
FJ
Montani
Jean-Pierre
JP
Dick
Bernhard
B
Frey
Brigitte M
BM
Ferrari
Paolo
P
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D006977:Hypertension, Renal / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017673:Sodium Chloride, Dietary / Q000494:pharmacology* / Q000652:urine
D017673:Sodium Chloride, Dietary; C096314:tetrahydro-11-dehydrocorticosterone; C003676:tetrahydrocorticosterone; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003345:Corticosterone