Natriuretic peptide receptors A and B have different cellular distributions in rat kidney

Ritter, Detlef; Dean, Alan D.; Gluck, Stephen L.; Greenwald, James E.

doi:10.1038/ki.1995.474

Cited by 34 publications

(27 citation statements)

References 28 publications

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“…CNP is inactivated by NEP, and therefore local CNP may be degraded before arrival in the lumen of the collecting duct, offering a plausible explanation for its weak natriuretic effect. 29 In summary, we demonstrated that CNP expression tends to be higher immediately after ligation and declined at later time points. A high level of CNP may contribute to the elevated expression of NPR-B in the early phase of UUO.…”

Section: Discussionmentioning

confidence: 93%

Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy

Zhao

Wang

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction: C-type natriuretic peptide (CNP) selectively binds to the guanylyl cyclase coupled natriuretic peptide receptor (NPR)-B and exerts more potent antihypertrophic and antifibrotic properties. Elimination of CNP occurs mainly by neutral endopeptidase (NEP) and NPR-C. Methods:We established a rat model of unilateral ureteral obstruction (UUO) to examine the continuous change of the CNP expression and to assess the correlations of NPR-B, NPR-C, NEP with CNP in the obstructed kidneys. Results: The expressions of CNP mRNA and protein in the obstructed kidneys tended to be higher immediately after ligation and declined at later time points compared to sham-operated rats, measured by real-time polymerase chain reaction (PCR) and western blot analysis. Subsequent correlation analysis indicated that CNP mRNA was positively correlated with p<0.05). In addition, the increased expression of NPR-C (r=−0.943 and −0.837 for mRNA and protein respectively, p<0.05) and NEP (r=−0.687 and −0.823 for mRNA and protein respectively, p<0.05) were accompanied by a significant decline in CNP. Conclusions: A high level of CNP may contribute to the elevated expression of NPR-B in the early phase of UUO. More interestingly, paradoxical expressions of NPR-C and NEP may account for the decline of CNP in the obstructed kidneys.

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Section: Discussionmentioning

confidence: 93%

Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy

Zhao

Wang

et al. 2013

J Renin Angiotensin Aldosterone Syst

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“…The latter hypothesis may explain why renal NPR-Bs are not detectable with autoradiography 50 or radioreceptor-binding assay. 53 In addition, Ritter et al 52 found that the cellular distribution of NPR-Bs is quite different from that of NPRAs. NPR-As were detected in glomeruli, thin limbs of Henle loop, cortical collecting ducts, and inner medullary collecting duct.…”

Section: Discussionmentioning

confidence: 99%

“…This is in keeping with the evidence that within the kidney, CNP stimulates less cGMP generation than does ANP, 49,50 even if NPR-Bs are expressed in the kidney. 49,51,52 This blunted response may be due to either an intrinsically low guanylate cyclase activity of NPR-B or a low number of these receptors. The latter hypothesis may explain why renal NPR-Bs are not detectable with autoradiography 50 or radioreceptor-binding assay.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose C-Type Natriuretic Peptide Does Not Affect Cardiac and Renal Function in Humans

et al. 1998

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Abstract-In experimental animals, C-type natriuretic peptide (CNP) has vasodilating, hypotensive, and natriuretic activities.The role of circulating CNP in the overall regulation of cardiac and renal function in humans is less defined, in both health and disease. We measured cardiac volumes, diastolic and systolic functions, systemic (Doppler echocardiography) and renal hemodynamics, intrarenal sodium handling (lithium clearance method), plasma and urinary cGMP, plasma renin concentration, and plasma aldosterone level in six healthy volunteers (mean age, 33Ϯ3 years) receiving CNP (2 and 4 pmol/kg per minute for 1 hour each) in a single-blind, placebo-controlled, random-order, crossover study. During CNP infusion, plasma CNP increased from 1.17Ϯ0.23 to 41.52Ϯ4.61 pmol/L (ie, 4-to 10-fold higher levels than those observed in disease states) without affecting plasma and urinary cGMP, cardiac volumes, dynamics of left and right heart filling, cardiac output, arterial pressure, renal hemodynamics, intrarenal sodium handling, sodium excretion, or plasma levels of renin and aldosterone. The finding that increments in plasma CNP within the pathophysiological range have no effects on systemic hemodynamics, renal function, or the renin-angiotensin system do not support the hypothesis that CNP may act as a circulating hormone in humans. (Hypertension. 1998;31:802-808.)Key Words: echocardiography Ⅲ hemodynamics Ⅲ systole Ⅲ diastole Ⅲ natriuretic peptides T he natriuretic peptide system consists of at least three structurally homologous peptides: ANP, BNP, and CNP. ANP and BNP are cardiac hormones that contribute to the overall regulation of cardiovascular homeostasis and fluid volume due to their natriuretic, vasodilating, and renin-aldosterone-inhibiting actions.1,2 CNP, first isolated in porcine brain, 3 is a 22-amino acid peptide that shares a high homology with ANP and BNP within the ring structure but lacks the carboxyl-terminal extension. 3Outside the central nervous system, CNP is mainly produced by the vascular endothelium, [4][5][6] in which it is thought to act as a local paracrine factor for the control of vascular tone. Endothelial production of CNP is remarkably augmented by various cytokines and growth factors such as transforming growth factor-␤ and tumor necrosis factor-␣, suggesting that CNP may be of pathophysiological relevance in various vascular disorders.7 Like the other natriuretic peptides, CNP is detectable in plasma of healthy subjects, although at much lower concentrations than ANP and BNP. 4,8 -13 Plasma CNP levels are increased in patients with chronic renal failure, 9,10 septic shock, 11 and cor pulmonale, 12 raising the possibility that CNP may be a circulating hormone involved in the regulation of cardiovascular function. CNP exerts its biological effects by selectively activating the NPR-B, 14,15 leading to an increase in cGMP in target cells. In experimental animals, the administration of CNP induces vasodilation of both arteries and veins 16 ; reduces cardiac filling pressures, 17 CO,18,1...

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“…17 GC-A is abundantly expressed in blood vessels and the heart 17 ; within the kidney, it is localized in glomeruli, thin limbs of Henle's loop, cortical collecting ducts, and inner medullary collecting ducts. 18 In glomeruli, GC-A is expressed in mesangial cells and podocytes. 18 GC-A-deficient mice show chronic salt-independent elevation of BP by approximately 15-30 mmHg 19 and cardiac hypertrophy, 20 with virtually no natriuretic or diuretic response to acute volume expansion.…”

mentioning

confidence: 99%

“…18 In glomeruli, GC-A is expressed in mesangial cells and podocytes. 18 GC-A-deficient mice show chronic salt-independent elevation of BP by approximately 15-30 mmHg 19 and cardiac hypertrophy, 20 with virtually no natriuretic or diuretic response to acute volume expansion. 21 These studies clearly demonstrate essential roles for natriuretic peptide/GC-A signaling in BP regulation and acute volume handling through the kidney, but the role of GC-A in podocyte injury remains elusive.…”

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confidence: 99%

Natriuretic Peptide Receptor Guanylyl Cyclase-A Protects Podocytes from Aldosterone-Induced Glomerular Injury

Ogawa

Mukoyama

Yokoi

et al. 2012

Journal of the American Society of Nephrology

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Natriuretic peptides produced by the heart in response to cardiac overload exert cardioprotective and renoprotective effects by eliciting natriuresis, reducing BP, and inhibiting cell proliferation and fibrosis. These peptides also antagonize the renin-angiotensin-aldosterone system, but whether this mechanism contributes to their renoprotective effect is unknown. Here, we examined the kidneys of mice lacking the guanylyl cyclase-A (GC-A) receptor for natriuretic peptides under conditions of high aldosterone and high dietary salt. After 4 weeks of administering aldosterone and a high-salt diet, GC-A knockout mice, but not wild-type mice, exhibited accelerated hypertension with massive proteinuria. Aldosterone-infused GC-A knockout mice had marked mesangial expansion, segmental sclerosis, severe podocyte injury, and increased oxidative stress. Reducing the BP with hydralazine failed to lessen such changes; in contrast, blockade of the renin-angiotensin-aldosterone system markedly reduced albuminuria, ameliorated podocyte injury, and reduced oxidative stress. Furthermore, treatment with the antioxidant tempol significantly reduced albuminuria and abrogated the histologic changes. In cultured podocytes, natriuretic peptides inhibited aldosterone-induced mitogen-activated protein kinase phosphorylation. Taken together, these results suggest that renoprotective properties of the endogenous natriuretic peptide/GC-A system may result from the local inhibition of the renin-angiotensin-aldosterone system and oxidative stress in podocytes.

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Natriuretic peptide receptors A and B have different cellular distributions in rat kidney

Cited by 34 publications

References 28 publications

Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy

Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy

Low-Dose C-Type Natriuretic Peptide Does Not Affect Cardiac and Renal Function in Humans

Natriuretic Peptide Receptor Guanylyl Cyclase-A Protects Podocytes from Aldosterone-Induced Glomerular Injury

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