Is Dopamine a Physiological Natriuretic Hormone in the Dog?

Abstract

Both plasma and urinary dopamine and noradrenaline were measured as free and sulphate conjugates, by a radioenzymatic method, before and during extracellular volume expansion (ECVE) with hypo-, iso- or hyper-tonic fluid (usually sodium chloride solution) in dogs. During ECVE there was a decrease in plasma catecholamine concentration. For all cases except noradrenaline, this is probably due to a dilution phenomenon since when results were expressed as pg/mg of protein, ECVE had no effect. This change in noradrenaline accounted for the increase in the dopamine/noradrenaline ratio. As expected, there was an increase in the urinary excretion of dopamine during ECVE with both iso- and hyper-tonic fluid. This increase was not observed in the group of dogs given hypotonic fluid, although the increase of fractional excretion of sodium was of a similar order of magnitude. The increase in the urinary excretion of dopamine was apparently not affected by an increase in plasma sodium concentration and/or osmolality. The demonstrated dissociation between sodium and dopamine in urine does not support a physiological role for dopamine in renal handling of sodium during ECVE, and raises the question of its specificity.

Urinary Dopamine and Renal Handling of L–DOPA in Fasted Spontaneously Hypertensive Rats

“…Inhibition of Na + , K + -ATPase [4] and/or Na + -H + exchanger [5] were suggested as tubular mechanisms of the DA-induced natriuresis. However, several studies could not or only partially confirm this idea [6][7][8][9][10]. The reason for the conflicting data may be that the natriuretic effect of renal DA depends on certain conditions, like moderate sodium loading or slight volume expansion [6,11].…”

“…However, several studies could not or only partially confirm this idea [6][7][8][9][10]. The reason for the conflicting data may be that the natriuretic effect of renal DA depends on certain conditions, like moderate sodium loading or slight volume expansion [6,11]. A crucial role of the kidney in the pathogenesis of hypertension was suggested by observations in human kidney allograft recipients and transplantation studies in spontaneously hypertensive rats (SHR) [12,13].…”

Metoclopramide Does Not Affect Renal Function and Atrial Natriuretic Peptide Release in Response to Acute Saline Loading in Conscious Rats

“…Acute ECFV expan sion with i.v. saline infusion, a condition in which the renal sympathetic tone is consider ably suppressed [22], was shown to be accom panied by increased urinary DA excretion [5][6][7][8][9][10], As the plasma levels of DA remain unde tectable [22] or decrease [10] under these con ditions, the production of endogenous DA within the kidney must have increased [23]. In PCT cells, L-amino acid decarboxylase converts L-DOPA to DA [24,25], This locally formed DA is thought to inhibit Na-KATPase activity [26,27] in PCT cells [28,29] by involving DA-1 and/or DA-2 receptors [30] and to participate in proximal tubular fluid and Na absorption [31].…”

“…a decrease in colloid oncotic and increase in hydrostatic pressures within peritubular cap illaries [2,3], as well as to the release of natri uretic substances [4], Exogenous dopamine (DA) raises renal blood flow and GFR as well as renal Na excre tion. Since the natriuresis during ECFV ex pansion is accompanied by a rise in urinary DA excretion [5][6][7][8][9], it is argued that renal DA acts as a natriuretic factor [10], possibly in a paracrine fashion [11], In fact, Pelayo et al [12] showed in the rat that m-flupenthixol, a predominant DA-1 receptor antagonist, blunts the natriuresis of acute Ringer infu sion, and Krishna et al [13] demonstrated in man that metoclopramide (MCP), a predomi nant DA-2 receptor antagonist, attenuates the natriuresis that follows head-out water im mersion. Moreover, it was claimed that in the rat DA mediates the renal effects of atrial natriuretic peptide (ANP) [14] released from the heart atria in response to an acute fluid load [15], Both, DA-1 and DA-2 receptor subtypes have been identified in the kidney [16,17] and may thus play a role in renal hemody namic and functional adaptations to changes in Na balance.…”

Effects of an Intravenous Infusion of Noradrenaline on the Plasma Concentration of Free and Sulfoconjugated Catecholamines in Anesthetized Dogs

“…1984;Dunne et al. 1984;Cuche et al, 1983Cuche et al, , 1985, Thus, sulfate conjugation is usually considered as a metabolic pathway for inacti vating CA and making their elimination eas ier. This is likely to be incomplete because the organism has a sulfatase system.…”