Differentiation of Noradrenergic and Dopaminergic Nerves in the Rat Kidney: Evidence Against Significant Dopaminergic Innervation

Abstract

In the rat kidney catecholaminergic nerve elements were identified by fluorescence histochemistry in perivascular plexuses around corticula arteries and juxtaglomerular arterioles and in medullary vascular bundles. Fluorescence was abolished in all areas 24 h after treatment with 6-hydroxydopamine (6-OHDA; 150 mg/kg i.v.). Protection of noradrenergic endings from destruction by 6-OHDA was afforded by pretreatment with desipramine (DMI; 25 mg/kg i.p.) which restored fluorescence towards control levels. By semiquantitative analysis fluorescence was identical in juxtaglomerular regions but slightly reduced around larger vessels in (DMI + 6-OHDA)-treated rats when compared to controls. Changes in tissue noradrenaline content, but not dopamine content, paralleled the changes in nerve fluorescence. Noradrenaline content was 4.10 pmol/mg protein (s.e.m. = 0.22, n = 32) in controls and was reduced by 90% to 0.40 pmol/mg (s.e.m. = 0.05, n = 23) in 6-OHDA-treated and by 26% to 3.01 pmol/mg (s.e.m. = 0.21, n = 23) in (DMI + 6-OHDA)-treated rats. Kidney dopamine content was 0.38 pmol/mg protein (s.e.m. = 0.05, n = 32) in controls and was reduced by 55% to 0.18 pmol/mg (s.e.m. = 0.02, n = 17) in 6-OHDA-treated and by 53% to 0.17 pmol/mg (s.e.m. = 0.02, n = 23) in (DMI + 6-OHDA)-treated rats. The renin response to haemorrhage was examined in pentobarbitone sodium-anaesthetized rats as a test of functional integrity of renal nerves in the three groups. Progressive 1 ml haemorrhages (to total blood loss of 4 ml, 1.3% body weight) resulted in similar increases in plasma renin activity in controls and (DMI + 6-OHDA)-treated animals but the response was significantly attenuated in 6-OHDA-treated rats. Renal catecholaminergic nerves appear to be predominantly noradrenergic. It is doubtful if a significant intrarenal dopaminergic system exists in the rat.

Differential effect of guanethidine on dopamine and norepinephrine in rat peripheral tissues

“…Studies using whole rat kidney found that about half of the total renal DA content was removed by denervation (McGrath et al, 1983;Stephenson et al, 1982) a finding which is in line with the 41% DA loss we have observed in the present report after destruction of noradrenergic nerves by guanethidine (Fig. 2).…”

Production and Excretion of Dopamine by the Isolated Perfused Rat Kidney

“…As the perfusion medium contained no endogenous dopamine or likely precursors (/-dopa, do pamine conjugates) the urinary dopamine must come from kidney dopamine or pre cursors. The levels of dopamine measured in the kidney (about 9 ng/gorl5 ng/kidney)are similar to those obtained by others [6,[24][25][26] and probably insufficient to ex plain the measured dopamine excretion (20 ng/kidney) even if all the tissue dopa mine was excreted in the urine and not removed by other mechanisms, such as me tabolism. Renal /-dopa seems a likely pre cursor for urinary dopamine given (a) its renal content (20 ng/g or 35 ng/kidney) sim ilar to that obtained by Dr. B. McGrath [pers.…”

“…It seems unlikely that dopamine was be ing produced in noradrenergic nerve tissue as (a) in these experiments 6-OH dopamine treatment reduced kidney noradrenaline content to levels where catecholamine fluo rescence is abolished [25] and to those levels seen with surgical denervation: all suggest ing (near) complete sympathectomy, and (b) /-dopa produced a similar increase in uri nary dopamine in chemically and surgically denervated kidneys.…”

“…Whether dopamine was being produced in dopaminergic nerve tissue is less clear, particularly given some doubt about the do paminergic innervation of kidney tubules, based on: (a) the low ratio of dopamine to noradrenaline in the kidney, which is con sistent with mainly noradrenergic, rather than dopaminergic, innervation [26]; (b) desipramine, which protects noradrenergic but not dopaminergic nerve endings from 6-OH dopamine, completely prevents the loss of fluorescence with 6-OH dopamine treat ment [25], However, neither of these argu ments exclude a quantitatively small dopa minergic innervation. It should be noted that there is no direct evidence for dopaminergic innervation of the kidney tubules and the evidence for vascular innervation is based largely on pharmacological studies [2], The localization of the kidney dopamine is also uncertain, although at least some may be intraneuronal (either noradrenergic or dopa minergic) as 6-OH dopamine reduces renal dopamine in some [6,26] but not all [26. and these studies] rats.…”

Effects of Dopamine on Renal Function in the Rat Isolated Perfused Kidney

“…The sources of this renal dopamine have been variously attributed to acid labile conjugates and free L-dopa circulating in plasma (Baines & Chan 1980;Brown & Allison 1981), spillover from noradrenergic endings (Baines & Morgunov 1980), renal dopaminergic endings (Bell er al. 1978;Dinnerstein et al 1979) or predominantly from non-neuronal tissue (Stephenson et al 1980;McGrath et al 1983). The demonstration of dopamine release into the urine of the isolated perfused kidney (controls) strongly suggests that the kidney is the major source of urinary dopamine rather than any extraction from plasma as the perfusate in this system contains no dopamine, dopamine conjugates or L-dgpa.…”