Relationship between Urinary Dopamine Production and Natriuresis after Acute Intravascular Volume Expansion with Sodium Chloride in Dogs*

Abstract

The role of renal production of dopamine in mediating the natriuretic response to acute vascular volume expansion was investigated. The effect of infusion of 0.9% saline (30 ml/kg X h) over 2 h on urine excretion of sodium and catecholamines, as well as other hemodynamic and renal function parameters, was examined in seven dogs during control and carbidopa (1 mg/kg every 8 h for 24 h before saline infusion) treatment periods. Acute vascular volume expansion with saline resulted in a rise (P less than 0.01) in the renal excretion of dopamine and a depression (P less than 0.01) in renal excretion of norepinephrine which paralleled the natriuretic response to saline infusion. Epinephrine excretion was not altered by saline infusion. Carbidopa treatment was not associated with changes in left ventricular filling pressure, arterial blood pressure, glomerular filtration rate, renal blood flow, renal excretion of norepinephrine or epinephrine. However, carbidopa eliminated the increase in renal production of dopamine and markedly attenuated the natriuretic response to saline infusion. Since carbidopa blocks tissue conversion of dopa to dopamine, it appears that renal production of dopamine is an important mechanism mediating the natriuretic response to acute volume expansion.

Chronic regulation of the renal Na+/H+exchanger NHE3 by dopamine: translational and posttranslational mechanisms

“…Maneuvers that chronically disrupt DA-dependent natriuresis such as blockade of DA generation by inhibitors of aromatic amino acid decarboxylase (14,95), pharmacological antagonism of dopamine receptors (51,55,70,84,94), and genetic deletion of DA receptors (DR 1 through DR 5 in isolation) all lead to systemic hypertension with a plethora of renal and extrarenal pathophysiological changes (1, 10,19,58,75,114,118,120). Some degree of impaired natriuresis has been described in several although not all of the single DA receptor gene deletion models (10,98).…”

“…Renal DA generation is increased in response to acute saline infusion (55,95) and the renal natriuretic response to a Na ϩ load is attenuated by antagonists of the type I DA receptor (DR 1 ) (56). Chronic Na ϩ loading increases renal DA excretion and natriuresis in rodents and humans (44,105), and pharmacological or genetic disruption of the DA 1 or DA 2 receptors leads to impaired natriuresis and volume-dependent hypertension (116).…”

Acute regulation of renal Na+/H+ exchanger NHE3 by dopamine: role of protein phosphatase 2A

“…A multitude of cardiovascular, neurohumoral, and renal mechanisms may contribute to the phenotypes of these mice, but both D 1 -like and D 2 -like receptor deletions have been associated with sodium retention, extracellular fluid expansion, and salt-sensitive hypertension (1,6,42,54). The importance of the intrarenal autocrine/paracrine dopamine system in the natriuretic response to both acute and chronic sodium loading has also been demonstrated by pharmacological inhibition of the aromatic amino acid decarboxylase (8,53) and blockade of the renal dopamine receptors (28,29,39,47,49).…”

“…These studies demonstrate that PP2A is an integral and critical participant in the signal transduction pathway between dopamine receptor activation and NHE3 inhibition. natriuresis; sodium transport; signal transduction THE INTRARENAL AUTOCRINE/PARACRINE dopamine natriuretic system is critical for mammalian sodium homeostasis (5,8,28,29,37,39,47,49,53). The dopamine precursor 3,4-dihydroxy-Lphenylalanine (L-DOPA) is taken up from the glomerular filtrate and plasma into the proximal tubule (48, 50), decarboxylated to dopamine by the action of the cytoplasmic aromatic amino acid decarboxylase (61), and dopamine is extruded into the urinary lumen as well as the interstitial space (43,51,58).…”

Dopamine Acutely Stimulates Na+/H+Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles

“…In addition to its role in maintaining sodium homeostasis under normal conditions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), defects in the renal paracrine/ autocrine DA axis have been demonstrated and postulated to contribute to certain forms of polygenic hypertension in both rodents (77)(78)(79)(80)(81)(82)(83)(84)(85)(86) and humans (87)(88)(89)(90)(91)(92). In the proximal tubule where 50 -60% of NaCl and water is reabsorbed, DA inhibits the basolateral membrane Na ϩ ,K ϩ -ATPase (34 -38), which is the primary driving force for transepithelial Na ϩ absorption.…”