Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension.
Since dopamine receptors are important in the regulation of renal and cardiovascular function, we studied the cardiovascular consequences of the disruption of the D3 receptor, a member of the family of D2-like receptors, expressed in renal proximal tubules and juxtaglomerular cells. Systolic and diastolic blood pressures were higher (approximately 20 mmHg) in heterozygous and homozygous than in wild-type mice. An acute saline load increased urine flow rate and sodium excretion to a similar extent in wild-type and heterozygous mice but the increase was attenuated in homozygous mice. Renal renin activity was much greater in homozygous than in wild-type mice; values for heterozygous mice were intermediate. Blockade of angiotensin II subtype-1 receptors decreased systolic blood pressure for a longer duration in mutant than in wild-type mice. Thus, disruption of the D3 receptor increases renal renin production and produces renal sodium retention and renin-dependent hypertension.
Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007, USA.
L D
LD
Asico
C
C
Ladines
S
S
Fuchs
D
D
Accili
R M
RM
Carey
C
C
Semeraro
F
F
Pocchiari
R A
RA
Felder
G M
GM
Eisner
P A
PA
Jose
D000803:Angiotensin I / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D005838:Genotype; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D007606:Juxtaglomerular Apparatus / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009318:Natriuresis / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000235:genetics; D050637:Receptors, Dopamine D3; D012083:Renin / Q000097:blood / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; C493594:Drd3 protein, mouse; D011945:Receptors, Angiotensin; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012965:Sodium Chloride; D000803:Angiotensin I; D012083:Renin