Do renal tubular dopamine receptors mediate dopamine-induced diuresis in the anesthetized cat?
The aim of this study was to investigate whether the pentobarbitone anesthetized cat is a suitable preparation in which to characterize renal tubular dopamine receptors. Intravenous infusion of dopamine (10-100 micrograms/kg/min) resulted in a dose-related increase in mean blood pressure (MBP), urine output, sodium excretion (UNaV), and fractional sodium excretion (FENa). This diuretic effect occurred despite little change in glomerular filtration rate, suggesting that it is a consequence of decreased tubular reabsorption. Dopamine (10-100 micrograms/kg/min, i.v.) also induced marked dose-related falls in renal vascular conductance; however, renal blood flow was not significantly reduced. The increases in MBP, urine output, UNaV, and FENa induced by dopamine (10-100 micrograms/kg/min, i.v.), were unaffected by pretreatment of cats with either the selective dopamine DA1 or DA2 receptor antagonists, SCH 23390 (30 micrograms/kg, i.v.), or domperidone (100 micrograms/kg, i.v.) respectively. In contrast, pretreatment of cats with the nonselective alpha-adrenoceptor antagonist, phentolamine (1 mg/kg, i.v.) prevented dopamine-induced increases in urine output and MBP. Infusion of the selective dopamine DA1 receptor agonist fenoldopam (0.01-10 micrograms/kg/min) into the left renal artery failed to increase left renal vascular conductance, or left kidney urine output, UNaV, or FENa. In conclusion, this study provides no evidence for the involvement of renal tubular dopamine receptors in dopamine-induced diuresis in anesthetized cats. Rather, the diuretic effect appears to be linked to stimulation of alpha-adrenoceptors.
Clark
K L
KL
Department of Peripheral Pharmacology, Glaxo Group Research Limited, Ware, Hertfordshire, England.
Robertson
M J
MJ
Drew
G M
GM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002415:Cats; D004231:Diuresis / Q000187:drug effects*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004347:Drug Interactions; D005260:Female; D018818:Fenoldopam; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000294:innervation*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D004294:Domperidone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam; D004298:Dopamine; D010646:Phentolamine