Sympatho-inhibitory effects of r-l-glutamyl-l-dopa in conscious rabbits

Renal and total norepinephrine (NE) spillover rates were studied with [3H] NE kinetic method during graded r-l-glutamyl-l-dopa (gludopa) i.v. infusion in conscious rabbits. Mean arterial pressure (MAP) and heart rate (HR) remained constant during the experiment. Gludopa i.v. infusion at 25 and 100 micrograms.kg-1.min-1 produced marked increases in urinary dopamine (DA) excretion and renal DA content. Although renal venous DA rose after gludopa infusion, the arterial DA was not significantly altered. Arterial plasma gludopa and levodopa levels reached 0.9 +/- 0.5, 3.2 +/- 0.8 micrograms.ml-1 and 3.0 +/- 1.8, 10.1 +/- 5.1 ng.ml-1 at the lower and higher gludopa doses, respectively. Gludopa elicited a pronounced dose-related fall in renal NE spillover, which only accounted for about one half of the reduction in overall NE spillover rate. Renal NE content was doubled. These results indicated that gludopa decreased the renal and extrarenal NE spillover to plasma. This reduction may be mediated by intrarenally synthesized DA via presynaptic DA-2 and alpha-2 receptors, but could also be explained by some central sympatho-inhibitory mechanism.