Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide

Goy, Michael F.; Oliver, Peter; Purdy, Kit E.; Knowles, Joshua W.; Fox, Jennifer E.; Mohler, Peter J.; Qian, Xun; Smithies, Oliver; Maeda, Nobuyo

doi:10.1042/0264-6021:3580379

Cited by 29 publications

(27 citation statements)

References 49 publications

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“…However, there is evidence that BNP may act locally as an anti-fibrotic factor (Ogawa et al 2001) and that some of the actions of BNP may be mediated by an NPR preferential to BNP over ANF (Goy et al 2001). …”

Section: Discussionmentioning

confidence: 99%

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Casco

Veinot

Bold

et al. 2002

J Histochem Cytochem.

113

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S U M M A R YThe natriuretic peptides (NPs) ANF, BNP, and CNP have potent anti-proliferative and anti-migratory effects on vascular smooth muscle cells (SMCs). These properties make NPs relevant to the study of human coronary atherosclerosis because vascular cell proliferation and migration are central to the pathophysiology of atherosclerosis. However, the existence and cytological distribution of NPs and their receptors in human coronary arteries remain undetermined. This has hampered the development of hypotheses regarding the possible role of NPs in human coronary disease. We determined the pattern of expression of NPs and their receptors (NPRs) in human coronary arteries with atherosclerotic lesions classified by standard histopathological criteria as fatty streak/early atherosclerotic lesions, intermediate plaques, or advanced lesions. The investigation was carried out using a combination of immunocytochemistry (ICC), in situ hybridization (ISH), and semiquantitative polymerase chain reaction (PCR). Both by ICC and ISH, ANF was found in the intimal and medial layers of all lesions. BNP was highly expressed in advanced lesions where it was particularly evident by a strong ISH signal but weak ICC staining. CNP was demonstrable in all types of lesions, giving a strong signal by ISH and ICC. This peptide was particularly demonstrable in the endothelium, as well as in the SMCs of the intima, media, and vasa vasorum of the adventitia and in macrophages. By ISH, NPR-A was not detectable in any of the lesions but both NPR-B and NPR-C were found in the intimal and the inner medial layers. By RT-PCR, mRNA levels of all NPs tended to be increased in macroscopically diseased arteries, but only the values for BNP were significantly so. No significant changes in NPR mRNA levels were detected by PCR. In general, the signal intensity given by the NPs and their receptors by ICC or ISH appeared dependent on the type of lesion, being strongest in intermediate plaques and decreasing with increasing severity of the lesion. This study constitutes the first demonstration of NPs and NPR mRNAs in human coronary arteries and supports the existence of an autocrine/paracrine NP system that is actively modulated during the progression of atherosclerotic coronary disease. This suggests that the coronary NP system is involved in the pathobiology of intimal plaque formation in humans and may be involved in vascular remodeling.

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Section: Discussionmentioning

confidence: 99%

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Casco

Veinot

Bold

et al. 2002

J Histochem Cytochem.

113

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“…(2) Some tissues of GC-A Ϫ/Ϫ mice (ie, the testis and adrenal gland) retain significant high-affinity cGMP responses to BNP. This residual response cannot be accounted for by GC-B or any other known mammalian membrane GC, 59 suggesting that an as-yetunidentified receptor may exist that specifically recognizes BNP.…”

Section: Vascular Effectsmentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

241

161

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Abstract-Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases. (Circ Res. 2003;93:700-709.)

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“…Results were standardized per milligram protein, as measured by the Lowry method described previously (12). Guanylyl cyclase activity (basal and BNP stimulated) was measured in membranes isolated from whole hearts (DN-NPRA, n ϭ 4 and WT-NPRA, n ϭ 4 mice) using methods previously described (9). The membrane fractions were divided into four aliquots.…”

Section: Methodsmentioning

confidence: 99%

“…Unfortunately, interpretation of in vivo studies has been confounded by concomitant alterations in load. Furthermore, the density of NPRA receptors on cardiomyocytes is far less than that in lung, kidney, or adrenal tissues (9), raising questions regarding the biological significance of cardiomyocyte NPRA. Holtwick et al (13) reported that mice with cardiac-specific disruption of the NPRA displayed impaired relaxation and an exaggerated hypertrophic response to pressure overload, suggesting that, indeed, cardiomyocyte NPRA modulates cardiac structure and function independently of load.…”

mentioning

confidence: 99%

Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload

Patel

Valencik

Pritchett

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload. Am J Physiol Heart Circ Physiol 289: H777-H784, 2005. First published March 18, 2005 doi:10.1152/ajpheart.00117.2005.-Atrial (ANP) and brain (BNP) natriuretic peptides are hormones of myocardial cell origin. These hormones bind to the natriuretic peptide A receptor (NPRA) throughout the body, stimulating cGMP production and playing a key role in blood pressure control. Because NPRA receptors are present on cardiomyocytes, we hypothesized that natriuretic peptides may have direct autocrine or paracrine effects on cardiomyocytes or adjacent cardiac cells. Because both natriuretic peptides and NPRA gene expression are upregulated in states of pressure overload, we speculated that the effects of the natriuretic peptides on cardiac structure and function would be most apparent after pressure overload. To attenuate cardiomyocyte NPRA activity, transgenic mice with cardiac specific expression of a dominant-negative (DN-NPRA) mutation (HCAT D 893A) in the NPRA receptor were created. Cardiac structure and function were assessed (avertin anesthesia) in the absence and presence of pressure overload produced by suprarenal aortic banding. In the absence of pressure overload, basal and BNP-stimulated guanylyl cyclase activity assessed in cardiac membrane fractions was reduced. However, systolic blood pressure, myocardial cGMP, log plasma ANP levels, and ventricular structure and function were similar in wild-type (WT-NPRA) and DN-NPRA mice. In the presence of pressure overload, myocardial cGMP levels were reduced, and ventricular hypertrophy, fibrosis, filling pressures, and mortality were increased in DN-NPRA compared with WT-NPRA mice. In addition to their hormonal effects, endogenous natriuretic peptides exert physiologically relevant autocrine and paracrine effects via cardiomyocyte NPRA receptors to modulate cardiac hypertrophy and fibrosis in response to pressure overload. natriuretic peptides; diastole; hypertrophy; fibrosis ATRIAL (ANP) AND BRAIN (BNP) natriuretic peptides (NP) are of cardiomyocyte origin and stimulate production of the intracellular second messenger cGMP via binding to the natriuretic peptide A receptor (NPRA). The natriuretic peptide B receptor (NPRB) preferentially binds C-type NP of endothelial cell origin. A third receptor [natriuretic peptide C receptor (NPRC)] is not linked to guanylyl cyclase and serves as a clearance receptor that, along with digestion by ubiquitous neutral endopeptidases, clears NP from the circulation (27).Transcripts for all three NP receptors are present in cardiomyocytes and fibroblasts (20), and upregulation of cardiomyocyte NPRA mRNA with hypertrophy has been reported (3). Indeed, in vitro (14,17,30,31,34,38,40) and in vivo (16, 28, 41) studies suggest that the NP and the NP second messenger cGMP have anti-hypertrophic, anti-fibrotic, and prolusitropic effects on the heart. Unfortunately, interpretation of in ...

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Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide

Cited by 29 publications

References 49 publications

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Natriuretic Peptide System Gene Expression in Human Coronary Arteries

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload

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