Pathophysiological role of dopamine in the kidney: effects in diabetes mellitus and after contralateral nephrectomy.
Both insulin-dependent diabetes mellitus (IDDM) and unilateral nephrectomy (UNX) are associated with an increase in the glomerular filtration rate. Glomerular hyperfiltration has been linked to intraglomerular hypertension in both conditions, although it has only been linked to the development of nephropathy in diabetes. In this study, we examined the possibility of preventing diabetic nephropathy through early dopamine (DA) prodrugs treatment and we also investigated the participation of endogenous DA in the acute functional adaptation of the remaining kidney after UNX. In an animal model of IDDM (steptozotocin-treated Wistar rats), the early increase in the glomerular filtration rate was prevented by treatment with DA prodrugs (L-dopa or gludopa), an effect which was mimicked by fenoldopam (a D1 agonist) and suppressed by carbidopa and SCH 23390 (a D1 antagonist). An increase in endorenal DA synthesis and the subsequent stimulation of vascular D1 receptors appears to prevent early glomerular hyperfiltration in diabetic rats. However, in a long-term study lasting more than one year, streptozotocin-diabetic Wistar rats (unlike to diabetic Munich Wistar rats) failed to develop overt nephropathy characterized by albuminuria and systemic hypertension. During long-term treatment of diabetic rats with L-dopa, the renal availability of DA was diminished. The acute adaptation of the remaining kidney to UNX took the form of an early transient pressor effect with a moderate increase in the glomerular filtration rate and renal blood flow, and a marked decrease in tubular sodium reabsorption. SCH 23390 suppressed the hemodynamic and tubular responses to UNX, suggesting that endogenous DA plays a key role.
Institut de Pharmacologie, URA DO589 CNRS, Université Louis Pasteur, Faculté de Médecine, Strasbourg, France.
M
M
Barthelmebs
P
P
Mayer
A
A
Thomas
M
M
Grima
J L
JL
Imbs
D000222:Adaptation, Physiological; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000517:prevention & control* / Q000652:urine; D004298:Dopamine / Q000502:physiology* / Q000652:urine; D015259:Dopamine Agents / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000627:therapeutic use; D018818:Fenoldopam / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007980:Levodopa / Q000627:therapeutic use; D009392:Nephrectomy; D011355:Prodrugs / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011355:Prodrugs; D007980:Levodopa; D018818:Fenoldopam; D004298:Dopamine