Four-Hour Atrial Natriuretic Peptide Infusion in Conscious Rats: Effects on Urinary Volume, Sodium, and Cyclic GMP

Ht, Campbell; Bo, Lightfoot; Ah, Sklar

doi:10.3181/00379727-189-42813

Cited by 8 publications

(13 citation statements)

References 27 publications

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“…However, as mentioned above, ANP induced increased plasma membrane AQP2 expression. Moreover, the time course of ANP effects on diuresis and water excretion indicate that the effect is transient (6). Thus aldosterone-induced increased ANP secretion is not likely to be involved in the decreased apical AQP2 expression observed in the present study; 2) PGE 2 has been demonstrated to play an important role in antagonizing the effect of vasopressin on osmotic water permeability in the renal collecting duct.…”

Section: Discussionmentioning

confidence: 45%

Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

Nielsen¹,

Kwon²,

Prætorius³

et al. 2006

American Journal of Physiology-Renal Physiology

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increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus. Am J Physiol Renal Physiol 290: F438 -F449, 2006. First published September 13, 2005 doi:10.1152/ajprenal.00158.2005.-Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 Ϯ 14 ml/24 h), whereas spironolactone decreased (74 Ϯ 11 ml/24 h) urine production compared with rats treated with lithium only (120 Ϯ 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.aldosterone; connecting tubule; collecting duct; water metabolism; aquaporin 2 ALDOSTERONE AND VASOPRESSIN are two essential hormones in the regulation of body fluid homeostasis. Under normal conditions, renal water reabsorption is controlled through vasopressinmediated regulation of the water permeability in the renal connecting tubule (CNT) and collecting ducts (11,22). This occurs through a V 2 -receptor-mediated activation of the adenylate cyclase, leading to increased cAMP accumulation and protein kinase A (PKA) activation, promoting intracellular trafficking of the water channel aquaporin 2 (AQP2) to the apical plasma membrane and increased AQP2 protein expression (11,14,33). Aldosterone regulates sodium reabsorption in part through the mineralocorticoid receptor-mediated increase of the ␣-subunit of the epithelial sodium channel ENaC and increased ENaC traff...

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Section: Discussionmentioning

confidence: 45%

Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

Nielsen¹,

Kwon²,

Prætorius³

et al. 2006

American Journal of Physiology-Renal Physiology

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“…19 Prolonged infusion of ANP in rats was associated with increased natriuresis and diuresis during the first hour, which returned to baseline after 2 hours of infusion. 25 Urinary excretion of cGMP, the second messenger of ANP, remained elevated during ANP infusion, suggesting that the diminishing natriuretic and diuretic effects in response to ANP are independent of cGMP signaling. In addition, a transient increase in natriuresis and diuresis after prolonged ANP infusion was confirmed in healthy men.…”

Section: Discussionmentioning

confidence: 96%

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension

et al. 2017

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S alt-sensitive hypertension (SSH) is characterized by an increase in blood pressure (BP) in response to sodium load and is associated with an increased risk of cardiovascular events. [1][2][3] Owing to high dietary salt intake and genetic predisposition, salt sensitivity of BP is of particular clinical relevance in Asian populations. [4][5][6][7][8] Considering its pathophysiology, thiazide-type diuretics are the preferred antihypertensive agents for patients with SSH.9-11 However, conditions such as hyponatremia and hypokalemia caused by thiazide-type diuretics often contribute to morbidity and mortality, if left unrecognized. Hence, antihypertensive agents that improve urinary sodium excretion without altering electrolyte concentrations would be a better therapeutic option for patients with SSH. Among multiple pathophysiological mechanisms, a relative deficiency of atrial natriuretic peptide (ANP) is considered to result in sodium retention and a suboptimal vasodilatory response to sodium loading observed in patients with SSH.12-15 The renin-angiotensin-aldosterone system (RAAS) also plays a role in the pathogenesis of SSH by modulating renal sodium reabsorption.16 Therefore, enhancing the activity of natriuretic peptides along with inhibition of the RAAS may be an effective, Abstract-Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, doubleblind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6-and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: −20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulato...

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“…Furthermore, acute ANP infusions significantly increased urinary sodium excretion and peaked 15 min after the onset of ANP infusion and declined gradually after the peak but remained elevated compared with control (42). Of note, several studies have shown that diuresis and natriuresis induced by ANP are transient when ANP is given as continuous infusions or as repeated bolus injections in humans and animals because resistance to the diuretic and natriuretic actions of ANP develops after relatively brief periods of ANP infusion (7,13,41). This phenomenon may be related to the mechanism that the subcellular localization of ENaC increases after 90 min of ANP infusion (42).…”

Section: Discussionmentioning

confidence: 96%

ANP-mediated inhibition of distal nephron fractional sodium reabsorption in wild-type and mice overexpressing natriuretic peptide receptor

Zhao

Pandey

Navar

2010

American Journal of Physiology-Renal Physiology

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Atrial natriuretic peptide (ANP) elicits natriuresis; however, the relative contributions of proximal and distal nephron segments to the overall ANP-induced natriuresis have remained uncertain. This study was performed to characterize the effects of ANP on distal nephron sodium reabsorption determined after blockade of the two major distal nephron sodium transporters with amiloride (5 microg/g body wt) plus bendroflumethiazide (12 microg/g body wt) in male anesthetized C57/BL6 and natriuretic peptide receptor-A gene (Npr1) targeted four-copy mice. The lower dose of ANP (0.1 ng x g body wt(-1) x min(-1), n = 6) increased distal sodium delivery (DSD, 2.4 +/- 0.4 vs. 1.6 +/- 0.2 mueq/min, P < 0.05) but did not change fractional reabsorption of DSD compared with control (86.3 +/- 2.0 vs. 83.9 +/- 3.6%, P > 0.05), thus limiting the magnitude of the natriuresis. In contrast, the higher dose (0.2 ng x g body wt(-1) x min(-1), n = 6) increased DSD (2.8 +/- 0.3 mueq/min, P < 0.01) and also decreased fractional reabsorption of DSD (67.4 +/- 4.5%, P < 0.01), which markedly augmented the natriuresis. In Npr1 gene-duplicated four-copy mice (n = 6), the lower dose of ANP increased urinary sodium excretion (0.6 +/- 0.1 vs. 0.3 +/- 0.1 mueq/min, P < 0.05) and decreased fractional reabsorption of DSD compared with control (72.2 +/- 3.4%, P < 0.05) at similar mean arterial pressures (91 +/- 6 vs. 92 +/- 3 mmHg, P > 0.05). These results provide in vivo evidence that ANP-mediated increases in DSD alone exert modest effects on sodium excretion and that inhibition of fractional reabsorption of distal sodium delivery is requisite for the augmented natriuresis in response to the higher dose of ANP or in Npr1 gene-duplicated mice.

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Four-Hour Atrial Natriuretic Peptide Infusion in Conscious Rats: Effects on Urinary Volume, Sodium, and Cyclic GMP

Cited by 8 publications

References 27 publications

Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension

ANP-mediated inhibition of distal nephron fractional sodium reabsorption in wild-type and mice overexpressing natriuretic peptide receptor

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