Title

Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension

Document Type

Journal Article

Publication Date

8-1-1998

Journal

Journal of Clinical Investigation

Volume

102

Issue

3

DOI

10.1172/JCI3685

Keywords

Catecholamines; D receptor gene 3; Dopamine receptor; Renin

Abstract

Since dopamine receptors are important in the regulation of renal and cardiovascular function, we studied the cardio-vascular 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 (~ 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.

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