DISRUPTION OF THE DOPAMINE D-3 RECEPTOR GENE PRODUCES RENIN-DEPENDENTHYPERTENSION

Since dopamine receptors are important in the regulation of renal and cardiovascular function, we studied the cardiovascular consequences of the disruption of the D-3 receptor, a member of the family of D-2-lik e receptors, expressed in renal proximal tubules and juxtaglomerular c ells. Systolic and diastolic blood pressures were higher (similar to 2 0 mmHg) in heterozygous and homozygous than in wild-type mice. An acut e saline load increased urine flow rate and sodium excretion to a simi lar extent in wild-type and heterozygous mice but the increase was att enuated in homozygous mice. Renal renin activity was much greater in h omozygous than in wild-type mice; values for heterozygous mice were in termediate, Blockade of angiotensin II subtype-1 receptors decreased s ystolic blood pressure for a longer duration in mutant than in wild-ty pe mice. Thus, disruption of the D3 receptor increases renal renin pro duction and produces renal sodium retention and renin-dependent hypert ension.