Renal effects of exogenous dopamine: modulation by renal nerves and dopamine receptor antagonists.
The modulation of the renal response to exogenous dopamine by renal denervation (DNX) and dopamine receptor antagonists was investigated in thiopental-anesthetized Sprague-Dawley rats. Experiments were performed after reaching stable systemic hemodynamics and urinary flow rate. These conditions were obtained with an infusion rate of approximately 1.2% of body weight per hour. In the vehicle group (VHC) i.v. infusion of dopamine (1, 3 and 9 microg kg(-1) min(-1) significantly increased glomerular filtration rate (GFR), assessed by renal clearance of [3H]inulin, by 14+/-1.5, 16+/-1.6 and 31+/-2.6%, respectively. Infusion of 1 and 3 microg kg(-1) min(-1) dopamine did not change systemic hemodynamics while the highest dose elevated heart rate, potentially contributing to the GFR increase. The specific D1 receptor antagonist SCH 23390 (10 microg kg(-l) min(-1) i.v.) did not affect the GFR response to dopamine infusion. In contrast, domperidone (DOM; 8 microg kg(-1) min(-1) i.v.), a specific, peripherally acting D2 antagonist, attenuated the glomerular hyperfiltration induced by the three doses of dopamine to 11+/-1.7, 13+/-2.2 and 16+/-2.6%, respectively. DNX diminished the GFR response to dopamine infusion to almost the same extent (11+/-2.8, 10+/-2.2 and 17+/-2.6%, respectively) as did DOM. When DNX animals were treated with DOM, the GFR responses to dopamine were further attenuated to non-significant increases. These additive effects of DOM and DNX suggest that two different mechanisms are involved. Both DNX and SCH 23390 decreased sodium excretion at baseline whereas DOM enhanced it. Under the present experimental condition, neither D1 nor D2 receptor blockade affected the natriuretic and diuretic response to dopamine. Whereas D1 receptors do not appear to be involved, both D2 receptors and renal nerves play a role in the renal hemodynamic response to dopamine, indicating involvement of both pre- and postsynaptical dopamine receptors.
Luippold
G
G
Department of Pharmacology, University of Tübingen, Germany.
Osswald
H
H
Mühlbauer
B
B
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003714:Denervation; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004294:Domperidone; D004298:Dopamine