Arterial blood pressure and renal sodium excretion in dopamine D3 receptor knockout mice.
Alterations in the dopaminergic system may contribute to the development of hypertension. Recently, it has been reported that pentobarbital-anesthetized mice with deficient dopamine D(3) receptors showed renin-dependent elevation in blood pressure. In a series of experiments, we evaluated the contribution of the dopamine D(3) receptor to the renal sodium excretion and arterial blood pressure behavior in conscious as well as anesthetized dopamine D(3) receptor knockout (-/-) mice. 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 D(3) 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 D(3) receptor (-/-) mice to their corresponding (+/+) mice, both on an HS diet. Clearance experiments with anesthetized D(3) 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 D(3) receptors are not significantly involved in the regulation of blood pressure associated with a deficiency in renal sodium elimination.
Staudacher
Torsten
T
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tübingen, Germany.
Pech
Bärbel
B
Tappe
Michael
M
Gross
Gerhard
G
Mühlbauer
Bernd
B
Luippold
Gerd
G
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D003243:Consciousness; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D010952:Plasma Substitutes / Q000494:pharmacology; D050637:Receptors, Dopamine D3 / Q000172:deficiency / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D013599:Systole; D013997:Time Factors
D010952:Plasma Substitutes; D050637:Receptors, Dopamine D3; D017673:Sodium Chloride, Dietary; D012965:Sodium Chloride