OBJECTIVETo investigate the mechanisms by which hypertension occurs in D(3) dopamine receptor null mice (D(3)-/-).

METHODSSeveral parameters, including blood pressure, renal sodium excretion, D(3) receptor protein and mRNA expression, plasma renin activity, norepinephrine concentration and AT(1) receptor expression were checked in D(3)-/- mice and their littermate wild type mice (D(3)+/+). Moreover, the vasorelaxant effect of D(3) receptor stimulation was measured with ex-vivo mesenteric artery isolated from Wistar-Kyoto rats.

RESULTSBlood pressure was higher in D(3)-/- mice compared with that in D(3)+/+ mice, salt-loading had no effect on blood pressure in both groups, at the last period, sodium excretion was lower in D(3)-/- mice as compared with D(3)+/+ mice, renal renin activity and AT(1) receptor expression were higher in D(3) -/- [corrected] mice than in D(3) +/+ [corrected] mice. In contrast, no difference of renal norepinephrine was found in two groups. When using angiotensin II subtype-1 receptor antagonist, the systolic blood pressure declined for a longer duration in mutant mice than in wild-type mice. Vaso-relaxation was found in ex-vivo isolated mesenteric artery when D(3) receptor was stimulated.

CONCLUSIONSElevation of blood pressure in D(3)-/- mice might be related with impaired renal sodium excretion and vaso-relaxation in resistance artery.