Reduction of glomerular hyperfiltration by dopamine D(2)-like receptor blockade in experimental diabetes mellitus.
BACKGROUND
Dopamine D(2)-like receptors are involved in the physiological response of renal haemodynamics to amino-acid infusion. The present study was performed to investigate whether domperidone, a D(2)-like receptor antagonist, modulates the pathological hyperfiltration in experimental diabetes mellitus.


METHODS
Renal function was studied in anaesthetized rats 2 weeks after induction of moderate diabetes mellitus by streptozotocin, and in non-diabetic controls. Rats in both groups continuously received domperidone or vehicle via drinking water. Following infusion of Ringer's saline for measurement of baseline values, an i.v. amino-acid load was applied to investigate the renal functional reserve.


RESULTS
In vehicle-treated diabetic rats baseline glomerular filtration rate and renal plasma flow were significantly higher compared with controls (1.10+/- 0.04 vs. 0.83+/-0.02 (P<0.004) and 4.83+/-0.26 vs 3.32+/-0.24 ml/min/100 g body weight (bw) (P<0.001) respectively). Domperidone completely normalized glomerular filtration rate and renal plasma flow in diabetic rats to values observed in vehicle-treated controls (0.81+/-0.07 (P=0.740) and 3.35+/- 0.30 ml/min/100 g bw (P=0.889) respectively). In the clearance experiments, arterial blood pressure, urinary flow rate and sodium excretion did not significantly differ when comparing the four groups. However, in conscious rats, urinary flow rate and sodium excretion were significantly higher in diabetic rats compared with non-diabetic controls. In both non-diabetic groups, amino-acid infusion induced a significant glomerular hyperfiltration that was completely absent in diabetic rats, and restored by domperidone treatment. In conscious vehicle-treated diabetic rats urinary albumin excretion was enhanced (449.0+/-47.7 vs. 185.7+/- 18.1 microg/24 h in non-diabetic rats (P<0.001)) and significantly lowered in diabetic rats by domperidone treatment (109.8+/-15.4 microg/24 h (P<0.001)).


CONCLUSIONS
The data suggest that dopaminergic mechanisms are involved in the changes in renal haemodynamics during early experimental diabetes mellitus in rats.
Luippold
G
G
Department of Pharmacology, University of Tübingen, Tübingen, Germany.
Beilharz
M
M
Mühlbauer
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004294:Domperidone / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors
D001786:Blood Glucose; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004294:Domperidone