Disruption of the dopamine D5 receptor gene in mice increases BP and causes salt sensitivity. To determine the role of renal versus extrarenal D5 receptors in BP regulation, we performed cross-renal transplantation experiments. BP was similar between wild-type mice and wild-type mice transplanted with wild-type kidneys, indicating that the transplantation procedure did not affect BP. BP was lower among D5-/- mice transplanted with wild-type kidneys than D5-/- kidneys, demonstrating that the renal D5 receptors are important in BP control. BP was higher in wild-type mice transplanted with D5 -/- kidneys than wild-type kidneys but not significantly different from syngenic transplanted D5-/- mice, indicating the importance of the kidney in the development of hypertension. On a high-salt diet, all mice with D5-/- kidneys excreted less sodium than mice with wild-type kidneys. Transplantation of a wild-type kidney into a D5-/- mouse decreased the renal expression of AT 1 receptors and Nox-2. Conversely, transplantation of a D 5-/- kidney into a wild-type mouse increased the expression of both, suggesting that both renal and extrarenal factors are important in the regulation of AT1 receptor and Nox-2 expression. These results highlight the role of renal D5 receptors in BP homeostasis and the pathogenesis of hypertension.
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