Lack of renal dopamine D5 receptors promotes hypertension.
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.
Children's National Medical Center, Children's Research Institute, 111 Michigan Avenue NW, Washington, D.C., USA.
Laureano
L
Asico
Xiaojie
X
Zhang
Jifu
J
Jiang
David
D
Cabrera
Crisanto S
CS
Escano
David R
DR
Sibley
Xiaoyan
X
Wang
Yu
Y
Yang
Roslyn
R
Mannon
John E
JE
Jones
Ines
I
Armando
Pedro A
PA
Jose
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D008562:Membrane Glycoproteins; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; D050641:Receptors, Dopamine D5; D012964:Sodium; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases