Renal response to infusion of dopamine precursors in anaesthetized rats

Abstract

In the present study the renal response to intravenous infusion of the catecholamine precursors l-dihydroxyphenylalanine (l-DOPA) or l-tyrosine was investigated in thiopentone sodium-anaesthetized Sprague-Dawley rats. Glomerular filtration rate (GFR) was assessed by renal clearance of inulin, urinary concentration of dopamine (U_DAV) by HPLC and sodium excretion (U_NaV) by flame photometry. We found that basal U_DAV was 6.5 ± 0.5 pmol/min per 100 g body weight (mean ± SEM). Intravenous infusion of l-tyrosine at 0.1–3.0 μmol/min dose dependently enhanced U_DAV (17 ± 3 to 144 ± 14 pmol/ min respectively) with higher doses of l-tyrosine resulting in no further increase in U_DAV. Compared with l-tyrosine administration significantly lower doses of l-DOPA (0.07 to 35 nmol/min) caused increases in U_DAV which were orders of magnitude higher (18 ± 1 to 7800 ± 470 pmol/min, respectively) and did not show saturation characteristics. GFR did not change in response to l-tyrosine or l-DOPA infusion. No variations in urinary flow rate or in U_NaV could be observed which were significantly correlated to changes in U_DAV. In contrast, intravenous infusion of dopamine at a dose of 6 nmol/min significantly increased GFR by 35 ± 6.2% and urinary flow rate by over 2-fold. Immunohistochemistry with light microscopy revealed no tyrosine hydroxylase in the kidney. Therefore, dopamine synthesis in the tubular cells mainly depends on the renal supply of l-DOPA. The unchanged GFR and U_NaV in spite of large variations of U_DAV argue against the hypothesis that intratubular dopamine plays a functional role in the regulation of hemodynamics or sodium transport in the kidney. Renal dopamine excretion may rather represent an effective pathway for the elimination of catecholamine precursors from the plasma.