Acute Volume Expansion and Salt-Loading Studies in Rats

Abstract

Differences have been postulated for the mechanism of natriuresis due to atrial natriuretic peptide (ANP), salt loading with high salt diet (HS) and acute volume expansion (AcVE), in particular between AcVE and ANP based on the observed synergism between the two. Therefore the effects of and the interaction between the three were investigated in rats. ANP and AcVE produced the same natriuresis in HS as in normal salt (NS) rats and, in both, the actions of ANP and AcVe were significantly additive showing similarity in mechanisms. Synergism [(AcVE + ANP) – AcVE] was, however, present only in the NS rats. Proximal tubular sodium transport was the same with AcVE and ANP+AcVE suggesting that synergism is a property of more distal nephron segments. In conscious HS rats, plasma ANP was significantly less but natriuresis was higher than in NS rats. ANP therefore probably has some causative role in the natriuresis of AcVE but none in that of HS loading. Urinary dopamine was significantly increased by HS and further increased by AcVE in both NS and HS rats, the relationship between dopamine and natriuresis being significantly positive (r² = 0.328) reaching equivalent levels in both NS and HS rats. Systemic benserazide prevented the increase in urinary dopamine but only attenuated the natriuresis of AcVE. We conclude that HS does not potentiate the natriuresis of AcVE or ANP, synergism between AcVE and ANP is not a proximal tubule event and dopamine accounts for significant natriuresis of VE in addition to other natriuretic factors.

Renal effects of dopamine and ANP in high volume expanded rats

“…It is also possible that the acute natriuretic response to ANP has been amplified by volume expansion, probably through an increase in distal delivery of fluid. Therefore, the results of this study would agree with published findings that demonstrated that during large volume expansion (15% body weight) factors other than those acting in the proximal tubule could play a significant role in more distal nephron segments to produce final natriuresis (32) such as the renal nerves, aldosterone, renninangiotensin system, vasopressin , prostaglandins and physical factors (9,20,28,34).…”

Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion

“…Even if there is a clear relationship between blood pressure and extracellular salt and volume, blood pressure changes during acute volume expansion remain quite controversial 4,21 . There is evidence indicating that saline loading produces an increase in arterial pressure in awake and anaesthetized dogs, whereas other studies have shown that arterial pressure is not altered in anaesthetized rats 1,3,22 . The diverse haemodynamic responses to extracellular volume expansion are probably caused by the different experimental conditions.…”

Dopamine and Renal Function and Blood Pressure Regulation

“…A protein load (115) or feeding (420) increases urinary dopamine that may be secondary to an increase in l -DOPA synthesis. Most studies have shown that a low sodium diet is associated with low urinary dopamine, while a high sodium diet is associated with increased urinary dopamine (9, 11, 40, 42, 43, 86, 214, 253, 352, 420, 443, 504, 577, 654). This may be related to increased spillover of l -DOPA into the arterial blood (214,229), although plasma l -DOPA levels are not increased with high sodium diet.…”

“…There is a clear interaction between dopamine receptors and ANP. The natriuretic response to ANP requires an intact renal dopamine system (263, 392, 481, 504, 574, 659). The natriuretic effect of ANP is abolished by D 1 R but not D 2 R antagonists (246, 316, 375, 393, 463) or carbidopa, an inhibitor of dopamine synthesis (309).…”