期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 22, 期 1, 页码 82-89出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2010050533
关键词
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资金
- National Institutes of Health [HL068686, HL023081, HL074940, HL092196, DK039308]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL074940, R37HL023081, R01HL023081, R01HL092196, P01HL068686] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK039308] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS002263, ZIANS003028] Funding Source: NIH RePORTER
Disruption of the dopamine D-5 receptor gene in mice increases BP and causes salt sensitivity. To determine the role of renal versus extrarenal D-5 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 D-5(-/-) mice transplanted with wild-type kidneys than D-5(-/-) kidneys, demonstrating that the renal D-5 receptors are important in BP control. BP was higher in wild-type mice transplanted with D-5(-/-) kidneys than wild-type kidneys but not significantly different from syngenic transplanted D-5(-/-) mice, indicating the importance of the kidney in the development of hypertension. On a high-salt diet, all mice with D-5(-/-) kidneys excreted less sodium than mice with wild-type kidneys. Transplantation of a wild-type kidney into a D-5(-/-) 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 AT(1) receptor and Nox-2 expression. These results highlight the role of renal D-5 receptors in BP homeostasis and the pathogenesis of hypertension.
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