The renal urodilatin system: clinical implications

Forssmann, Wolf‐Georg; Meyer, Markus; Forssmann, Kristin

doi:10.1016/s0008-6363(01)00331-5

Cited by 100 publications

(49 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ANP has been approved in Japan for the management of acute decompensated CHF (7), whereas BNP has been approved for the same indication in the U.S. (10). Uro is currently in phase II clinical trails in Europe for the same clinical indication (13). Our current studies support the conclusion that in our model of overt CHF, renal resistance to natriuretic peptides in increasing rank order is BNP Ͻ Uro Ͻ ANP.…”

Section: Discussionsupporting

confidence: 74%

Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure

Chen¹,

Cataliotti²,

Schirger³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure. Am J Physiol Regul Integr Comp Physiol 288: R1093-R1097, 2005. First published December 30, 2004; doi:10.1152/ajpregu.00682.2004.-A hallmark of overt congestive heart failure (CHF) is attenuated cGMP production by endogenous atrial natriuretic peptide (ANP) with renal resistance to ANP. ANP and brain natriuretic peptides (BNP) are of myocardial origin, whereas urodilatin (Uro) is thought to be derived from kidney. All three peptides are agonists to the natriuretic peptide-A receptor. Our objective was to compare the cardiorenal and humoral actions of ANP, BNP, and Uro in experimental overt CHF. We determined cardiorenal and humoral actions of 90 min of intravenous equimolar infusion of ANP, BNP, and Uro (2 and 10 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) in three separate groups of anesthetized dogs with rapid ventricular pacinginduced overt CHF (240 beats/min for 10 days). BNP resulted in increases in urinary sodium excretion (UNaV) (2.2 Ϯ 0.7 to 164 Ϯ 76 eq/min, P Ͻ 0.05) and glomerular filtration rate (GFR) (27 Ϯ 4 to 52 Ϯ 11 ml/min, P Ͻ 0.05) that were greater than those with Uro (P Ͻ 0.05), whereas ANP did not result in increases in UNaV or GFR. Increases in plasma cGMP (25 Ϯ 2 to 38 Ϯ 2 pmol/ml, P Ͻ 0.05) and urinary cGMP excretion with BNP (1,618 Ϯ 151 to 6,124 Ϯ 995 pmol/min, P Ͻ 0.05) were similar to those with Uro; however, there was no change with ANP. Cardiac filling pressures were reduced in all three groups. These studies also support the conclusion that in experimental overt CHF, renal resistance to natriuretic peptides in increasing rank order is BNP Ͻ Uro Ͻ ANP.

show abstract

Section: Discussionsupporting

confidence: 74%

Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure

Chen¹,

Cataliotti²,

Schirger³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Cells of the distal nephron have been shown to harbor proANP gene transcripts and ANP immunoreactivity (50), and ANP immunoreactivity has been identified in the urine (51). Urinary ANP, termed urodilatin, is a product of the renal ANP gene with a 4-amino-acid N-terminal extension (supplied from the proANP precursor) linked to the core ANP peptide (52). As shown in Figure 10F, expression of proANP mRNA in the inner medulla is increased following 24 hours of water restriction, as is the excretion of urodilatin in urine ( Figure 10G) (urodilatin concentration in urine: control, 4.37 ± 0.64 pg/μl vs. dehydrated, 9.33 ± 1.01 pg/μl; P < 0.01), suggesting that locally generated ligand as well as increased expression of the NPR-A receptor (see above) contribute to the increased urinary excretion of sodium in the acutely dehydrated state.…”

Section: Figurementioning

confidence: 99%

Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents

Chen¹,

Grigsby²,

Law³

et al. 2009

J. Clin. Invest.

199

View full text Add to dashboard Cite

In various mammalian species, including humans, water restriction leads to an acute increase in urinary sodium excretion. This process, known as dehydration natriuresis, helps prevent further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. Serum-and glucocorticoid-inducible kinase (Sgk1), which is expressed in the renal medulla, is regulated by extracellular tonicity. However, the mechanism of its regulation and the physiological role of hypertonicity-induced SGK1 gene expression remain unclear. Here, we identified a tonicity-responsive enhancer (TonE) upstream of the rat Sgk1 transcriptional start site. The transcription factor NFAT5 associated with TonE in a tonicity-dependent fashion in cultured rat renal medullary cells, and selective blockade of NFAT5 activity resulted in suppression of the osmotic induction of the Sgk1 promoter. In vivo, water restriction of rats or mice led to increased urine osmolality, increased Sgk1 expression, increased expression of the type A natriuretic peptide receptor (NPR-A), and dehydration natriuresis. In cultured rat renal medullary cells, siRNA-mediated Sgk1 knockdown blocked the osmotic induction of natriuretic peptide receptor 1 (Npr1) gene expression. Furthermore, Npr1 -/-mice were resistant to dehydration natriuresis, which suggests that Sgk1-dependent activation of the NPR-A pathway may contribute to this response. Collectively, these findings define a specific mechanistic pathway for the osmotic regulation of Sgk1 gene expression and suggest that Sgk1 may play an important role in promoting the physiological response of the kidney to elevations in extracellular tonicity. IntroductionPersistent hypertonicity, typically reflecting a high extracellular sodium concentration, stresses mammalian cells due to the ensuing osmotic efflux of water that shrinks the cells and concentrates their contents. Under most conditions, the concentration of extracellular sodium in mammals is controlled primarily through regulation of water metabolism. As extracellular sodium and plasma tonicity rise, the thirst mechanism is activated, and secretion of the neurohypophyseal hormone vasopressin into plasma increases. Vasopressin binds to its cognate receptors in the collecting duct of the kidney, resulting in increased water retention.Following short-term water restriction, several mammals demonstrate an acute increase in urinary sodium excretion that is independent of changes in water metabolism. This response, termed dehydration natriuresis (1-11), plays an important role in preventing further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. A similar natriuresis is seen following infusion of hypertonic saline (12). Investigations to date have suggested a role for central versus peripheral osmoreceptors and blood-borne versus neural effectors in contributing to dehydration-induced natriuresis; however, the precise mechanism(s) underlying this natriuresis remains undefined.

show abstract

“…Ularitide binds to natriuretic peptide receptors located on medullary collecting duct cells and vascular smooth muscle cells, which leads to increased diuresis, natriuresis, and arterial and venous vasodilation [67]. Clinically, ularitide has been shown to induce natriuresis and at the same time decrease plasma concentrations of renin, aldosterone, and angiotensin II [68,69].…”

Section: Ularitidementioning

confidence: 99%

Pharmacotherapy of Heart Failure

Vittalrao

Thanusubramanian

et al. 2018

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Heart failure (HF) is one of the major problems related to heart diseases in the modern era. Multiple comorbidities such as coronary artery disease, hypertension, diabetes mellitus, and anemia have a great contribution in the development of HF. It is primarily two types systolic and diastolic HF. Insufficient or decreased pumping of the heart is systolic HF, whereas diastolic HF is because of lack of ability of the heart to relax or increased muscle inflexibility. The pathophysiology of HF is due to enhanced activity of sympathetic system, renin angiotensin system, and structural changes in the wall of ventricle. The two definite targets of medical treatment in HF are as follows: (1) Alleviation of obstructive (or) decreased output manifestations and replenishment of cardiac function. The drugs used are frusemide, thiazides, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), amrinone/milrinone, dopamine/dobutamine, levosimendan, digoxin, hydralazine, nitroprusside, nitrate, bisoprolol, metoprolol, nebivolol, and carvedilol.(2) Prevention of advancement of HF and extension of patient survival -drugs used are β blockers, ACE inhibitors/ARBs, spironolactone, and eplerenone.

show abstract

The renal urodilatin system: clinical implications

Cited by 100 publications

References 93 publications

Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure

Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure

Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents

Pharmacotherapy of Heart Failure

Contact Info

Product

Resources

About