Arterial blood pressure and renal sodium excretion in dopamine D3 receptor knockout mice

Abstract

Alterstions in the dopaminergic system may contribute to the development of hypertension. Recently, it has been reported that pentobarbital-anesthetized mice with deficient dopamine D3 receptors showed renin-dependent elevation in blood pressure. In a series of experiments, we evaluated the contribution of the dopamine D3 receptor to the renal sodium excretion and arterial blood pressure behavior in conscious as well as anesthetized dopemine D3 receptor knockout (-/-) mica. The blood pressure measuring study was designed as a cross-over trial to investigate the influence of different sodium loads. The animals were fed a normal salt diet (0.6% NaCl, NS) for 1 week and afterwards a low (0.2% NaCl, LS) or a high salt diet (4.6% NaCl, HS) for 2 weeks. After the third week, the animals were switched to the corresponding protocol. Systolic blood pressure in conscious (-/-) mice measured by tail-cuff plethysmography was not different from that of wild-type (+/+) animals, irrespective of the time course or the salt diet. In another experiment, challenge of an acute sodium loading per gavage in conscious D3 receptor (-/-) and (+/+) animals on HS or NS diet did not show significant differences in renal sodium excretion between the two genotypes. Additionally, animals were fed an NS diet for 1 week and an HS diet for another week. As expected, sodium excretion significantly increased after the change from the NS to the HS diet. A slightly lower urinary sodium excretion was observed when comparing D3 receptor (-/-) mice to their corresponding (+/+) mica, both on an HS diet. Clearance experiments with anesthetized D3 receptor (-/-) and (+/ +) mice were performed to investigate the renal sodium excretion capacity, when exposed to a moderate volume expansion (VE). Urinary sodium excretion increased in response to the VE; however, no difference were observed between the two genotypes. Taking these results together, we conclude that in the present animal model renal dopamine D3 receptors are not significantly involved in the regulation of blood pressure associated with a deficiency in renal sodium elimination.