Abstract 1752: Cross-transplantation Studies Demonstrate the Role of Renal Dopamine D5 Receptors in Hypertension
We have already reported that disruption of the dopamine D5 receptor (D5R) gene in mice increases blood pressure (BP) and causes salt sensitivity. To determine the role of the renal D5R in the regulation of BP we performed cross-renal transplantation experiments. We studied four groups of mice:
D5+/+ kidney into D5−/− body (n = 9);
D5−/− kidney into D5+/+ body (n = 13); 3) D5−/− kidney into D5−/− body (n = 6); 4) D5−/− kidney into D5−/− body as controls (n = 7).
Studies were performed at least two weeks after transplantation. All mice had normal serum and urine creatinine levels, glomerular filtration rates were within the normal range, and there were no anatomical/histological abnormalities in the transplanted kidneys. Mice with D5−/− kidneys transplanted into D5−/− bodies had systolic BPs similar to those in D5−/− unmanipulated mice (98 ± 1 and 97 ± 3 mmHg [n = 6], respectively), indicating that the transplantation and its consequences (e.g., renal denervation) did not affect BP. Mice with D5−/− kidneys transplanted into D5−/− bodies had lower systolic BP than that observed in D5−/− kidneys to D5−/− bodies (109 ± 4 vs. 128 ± 3, p < 0.05). This indicates the importance of renal D5R in the regulation of BP. Mice with D5−/− kidneys transplanted into D5−/− bodies had higher systolic BP than those in mice with D5−/− kidneys transplanted to D5−/− bodies (117±3 vs. 98 ± 1; p < 0.05). This indicates the importance of the kidney in the development of hypertension. Mice with D5−/− kidneys transplanted into D5−/− bodies had systolic BP higher than that in the other groups and similar to unmanipulated D5−/− mice (128 ± 3 and 124 ± 2[n=6]). This indicates that D5R are involved in renal and extra-renal mechanisms that are important in the regulation of BP. Mice were also studied after salt loading (1 week, 6% NaCl). There was no increase in BP after salt loading in any of the groups, unlike the increase in BP in unmanipulated D5−/− mice, indicating that renal nerves are needed to impart salt sensitivity. When on high salt diet, mice with D5−/− kidneys whether they are in D5−/− or D5−/− bodies excreted less sodium than mice with D5−/− kidneys (2.1 ± 0.5 vs. 3.9 ± 0.6 mEq/mg creatinine, p < 0.03). Our results highlight the role of renal D5R in the regulation of BP as well as in the pathogenesis of hypertension.