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Lincoln R. Potter - One of the best experts on this subject based on the ideXlab platform.
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Determination of new phosphorylation sites within Natriuretic Peptide receptors using mass spectrometric methods
BMC Pharmacology, 2009Co-Authors: Andrea R. Yoder, Timothy J Griffin, Matthew D. Stone, Lincoln R. PotterAbstract:Background While it has long been know that phosphorylation of the kinase homology domain is a key regulatory mechanism of Natriuretic Peptide receptors, no biochemical proof for individual phosphorylation sites has been reported. Here, we describe biochemical verification of previously identified phosphorylation sites in both Natriuretic Peptide receptor A (NPR-A) and Natriuretic Peptide receptor B (NPR-B) as well as the identification of novel phosphorylation sites in both receptors.
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differential regulation of membrane guanylyl cyclases in congestive heart failure Natriuretic Peptide receptor npr b not npr a is the predominant Natriuretic Peptide receptor in the failing heart
Endocrinology, 2007Co-Authors: Deborah M Dickey, Darcy R Flora, Paula M Bryan, Yingjie Chen, Lincoln R. PotterAbstract:Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP) bind Natriuretic Peptide receptor (NPR)-A and decrease blood pressure and cardiac hypertrophy by elevating cGMP concentrations. Physiological responses to ANP and BNP are diminished in congestive heart failure (CHF) by an unknown mechanism. C-type Natriuretic Peptide (CNP) binding to NPR-B decreases cardiac hypertrophy, but the effect of CHF on NPR-B is unknown. Here, we measured ANP/NPR-A-dependent and CNP/NPR-B-dependent guanylyl cyclase activities in membranes from failing and nonfailing hearts. Transaortic banding of mice resulted in marked CHF as indicated by increased heart/body weight ratios, increased left ventricular diameters, and decreased ejection fractions. In nonfailed hearts, saturating ANP concentrations increased particulate guanylyl cyclase activity almost 10-fold, whereas saturating CNP concentrations increased activity 6.9-fold, or to about 70% of the ANP response. In contrast, in failed heart preparations, CNP elicited twice as much activity as ANP due to dramatic reductions in NPR-A activity without changes in NPR-B activity. For the first time, these data indicate that NPR-B activity represents a significant and previously unappreciated portion of the Natriuretic Peptide-dependent guanylyl cyclase activity in the normal heart and that NPR-B accounts for the majority of the Natriuretic Peptide-dependent activity in the failed heart. Based on these findings, we suggest that drugs that target both NPRs may be more beneficial than drugs like nesiritide (Natrecor) that target NPR-A alone.
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renal hyporesponsiveness to atrial Natriuretic Peptide in congestive heart failure results from reduced atrial Natriuretic Peptide receptor concentrations
American Journal of Physiology-renal Physiology, 2007Co-Authors: Paula M Bryan, Deborah M Dickey, Yingjie Chen, Lincoln R. PotterAbstract:Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide decrease blood pressure and cardiac hypertrophy by activating Natriuretic Peptide receptor A (NPR-A), a transmembrane guanylyl cyclase also known as guanylyl cyclase A. Inactivation of NPR-A is a potential mechanism for the renal hyporesponsiveness observed in congestive heart failure (CHF) but direct data supporting this hypothesis are lacking. We examined whether NPR-A activity was reduced in CHF, and if so, by what mechanism. In two separate trials, CHF was induced in mice by 8-wk transverse aortic constriction. Sham controls underwent surgery without constriction. The constricted animals developed severe heart failure as indicated by increased heart weight, increased left ventricular end diastolic and systolic diameters, and decreased left ventricular ejection fractions. Kidney membranes were assayed for guanylyl cyclase activity or used to purify NPR-A by sequential immunoprecipitation/SDS-PAGE. Maximal ANP-dependent guanylyl cyclase activities were reduced by 44 or 43% in kidney membranes from CHF animals in two independent trials. Basal cyclase activities were also reduced by 31% in the second trial. The amount of phosphorylated NPR-A was reduced by 25 or 24% in kidney membranes from CHF animals as well. SYPRO Ruby staining suggested that NPR-A protein levels were similar between treatments in the first trial. However, more accurate estimates of NPR-A protein levels by immunoprecipitation/Western analysis in the second trial indicated that NPR-A protein was reduced by 30%. We conclude that reduced NPR-A protein levels, not receptor dephosphorylation, explain the renal hyporesponsiveness to Natriuretic Peptides in CHF.
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atp independent activation of Natriuretic Peptide receptors
BMC Pharmacology, 2005Co-Authors: Laura K. Antos, Darcy R Flora, Sarah E Abbeyhosch, Lincoln R. PotterAbstract:Natriuretic Peptide receptor A (NPR-A) is an essential cardiovascular regulator that is stimulated by atrial Natriuretic Peptide and brain Natriuretic Peptide, whereas Natriuretic Peptide receptor B (NPR-B) stimulates long bone growth in a C-type Natriuretic Peptide-dependent manner. Many reports indicate that ATP is essential for NPR-A and NPR-B activation. Current models suggest that Natriuretic Peptide binding to receptor extracellular domains causes ATP binding to intracellular kinase homology domains, which derepresses adjacent catalytic domains. Here, we report 100-fold activation of Natriuretic Peptide receptors in the absence of ATP. Addition of a nonhydrolyzable ATP analog had no effect at early time periods (seconds) but increased cGMP production about two-fold after longer incubations (minutes), consistent with a stabilization, not activation, mechanism. These data indicate that ATP does not activate Natriuretic Peptide receptors. Instead, ATP increases activity primarily by maintaining proper receptor phosphorylation status, but also serves a previously unappreciated enzyme stabilizing function. from 2nd International Conference of cGMP Generators, Effectors and Therapeutic Implications Potsdam, Germany, 10–12 June, 2005
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phosphorylation dependent regulation of the guanylyl cyclase linked Natriuretic Peptide receptors
Peptides, 2005Co-Authors: Regine Potthast, Lincoln R. PotterAbstract:Natriuretic Peptides are a family of hormones/paracrine factors that regulate blood pressure, cardiovascular homeostasis and bone growth. The mammalian family consists of atrial Natriuretic Peptide (ANP), brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP). A family of three cell surface receptors mediates their physiologic effects. Two are receptor guanylyl cyclases known as NPR-A/GC-A and NPR-B/GC-B. Peptide binding to these enzymes stimulates the synthesis of the intracellular second messenger, cGMP, whereas a third receptor, NPR-C, lacks enzymatic activity and functions primarily as a clearance receptor. Here, we provide a brief review of how various desensitizing agents and/or conditions inhibit NPR-A and NPR-B by decreasing their phosphorylation state.
Kazuwa Nakao - One of the best experts on this subject based on the ideXlab platform.
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Natriuretic Peptide system an overview of studies using genetically engineered animal models
FEBS Journal, 2011Co-Authors: Ichiro Kishimoto, Kazuwa Nakao, Takeshi Tokudome, Kenji KangawaAbstract:The mammalian Natriuretic Peptide system, consisting of at least three ligands and three receptors, plays critical roles in health and disease. Examination of genetically engineered animal models has suggested the significance of the Natriuretic Peptide system in cardiovascular, renal and skeletal homeostasis. The present review focuses on the in vivo roles of the Natriuretic Peptide system as demonstrated in transgenic and knockout animal models.
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Natriuretic Peptide regulation of endochondral ossification evidence for possible roles of the c type Natriuretic Peptide guanylyl cyclase b pathway
Journal of Biological Chemistry, 1998Co-Authors: Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yoshihiro Ogawa, Michio Suda, Kiyoshi Tanaka, Kiyoshi Mori, Yoko Sakuma, Kohei Shiota, Kazuwa NakaoAbstract:Abstract The Natriuretic Peptide family consists of three structurally related endogenous ligands: atrial Natriuretic Peptide (ANP), brain Natriuretic Peptide (BNP), and C-type Natriuretic Peptide (CNP). The biological actions of Natriuretic Peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The Natriuretic Peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-Peptide GC-coupled Natriuretic Peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.
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c type Natriuretic Peptide as an autocrine paracrine regulator of osteoblast evidence for possible presence of bone Natriuretic Peptide system
Biochemical and Biophysical Research Communications, 1996Co-Authors: Michio Suda, Akihiro Yasoda, Yasato Komatsu, Yoshihiro Ogawa, Kiyoshi Tanaka, Mitsuo Fukushima, Koshi Natsui, Hiroshi Itoh, Kazuwa NakaoAbstract:Abstract C-type Natriuretic Peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial Natriuretic Peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [ 3 H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of “bone Natriuretic Peptide system.”
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increased plasma levels of brain Natriuretic Peptide in patients with acute myocardial infarction
Circulation, 1993Co-Authors: Etsuo Morita, Toshiyuki Matsumura, Michihisa Jougasaki, Michihiro Yoshimura, Hisao Ogawa, Masashi Mukoyama, Hirofumi Yasue, Kazuwa NakaoAbstract:BACKGROUNDBrain Natriuretic Peptide is a novel Natriuretic Peptide that is secreted predominantly from the ventricles, and its plasma levels have been shown to be markedly increased in patients with chronic congestive heart failure. This study was designed to examine the plasma levels of brain Natriuretic Peptide as well as atrial Natriuretic Peptide in patients with acute myocardial infarction.METHODS AND RESULTSWe examined the plasma levels of brain Natriuretic Peptide as well as atrial Natriuretic Peptide in 50 consecutive patients (36 men and 14 women; mean age, 66 years) with acute myocardial infarction over the time course of 4 weeks. The plasma level of brain Natriuretic Peptide was significantly increased on admission in patients with acute myocardial infarction compared with controls (92 +/- 28 versus 5.2 +/- 0.5 pg/mL, P < .01) and reached the peak level of 319 +/- 58 pg/mL at 16.4 +/- 0.7 hours after admission. Thereafter, the level decreased and then again increased, forming the second peak of...
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different secretion patterns of atrial Natriuretic Peptide and brain Natriuretic Peptide in patients with congestive heart failure
Circulation, 1993Co-Authors: Michihiro Yoshimura, Michihisa Jougasaki, Hisao Ogawa, Masashi Mukoyama, Kazuwa Nakao, Hirofumi Yasue, Ken Okumura, Hiroo ImuraAbstract:BACKGROUNDThe plasma levels of atrial Natriuretic Peptide (ANP) and brain Natriuretic Peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.METHODS AND RESULTSWe measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher...
Brian J Lipworth - One of the best experts on this subject based on the ideXlab platform.
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atrial Natriuretic Peptide and brain Natriuretic Peptide in cor pulmonale hemodynamic and endocrine effects
Chest, 1996Co-Authors: Robert I Cargill, Brian J LipworthAbstract:We have studied the hemodynamic and hormonal effects of atrial Natriuretic Peptide (ANP) and brain Natriuretic Peptide (BNP) in eight patients with cor pulmonale. Subjects were studied twice and were given a 20-min placebo infusion followed by either ANP or BNP (3 pmol/kg/min then 10 pmol/kg/min for 20 min each). Responses were measured after placebo infusion and following low-dose then high-dose ANP or BNP. Placebo infusion had no significant effects on either study day. Low-dose ANP and BNP significantly reduced mean pulmonary artery pressure (MPAP) from baseline by 3.7 mm Hg (95% confidence interval [CI], 1.4 to 6.1) and 3.0 mm Hg (95% CI, 0.6 to 5.4), respectively. High-dose ANP and BNP further reduced MPAP from baseline by 7.1 mm Hg (95% CI, 4.8 to 9.4) and 7.1 mm Hg (95% CI, 4.7 to 9.6), respectively. Effects on total pulmonary vascular resistance were similar. ANP and BNP had no confounding systemic hemodynamic effects. Plasma aldosterone was significantly suppressed from baseline by ANP: 156 pmol/L (95% CI, 93 to 220) after low dose, 275 pmol/L (95% CI, 207 to 343) after high dose; and by BNP: 92 pmol/L (95% CI, 30 to 153) after low dose, 159 pmol/L (95% CI, 98 to 220) after high dose. ANP and BNP produced dose-related pulmonary vasodilatation in patients with cor pulmonale, without worsening oxygen saturation or affecting systemic hemodynamics. ANP and BNP also exerted favorable neurohormonal effects by suppressing aldosterone.
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elevated levels of brain Natriuretic Peptide in acute hypoxaemic chronic obstructive pulmonary disease
Clinical Science, 1992Co-Authors: Chim C. Lang, Paul D Dhillon, J H Winter, W. J. Coutie, Allan D. Struthers, Brian J LipworthAbstract:1. Studies in vitro have recently shown that both atrial Natriuretic Peptide and brain Natriuretic Peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain Natriuretic Peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 +/- 0.4 kPa; arterial partial pressure of CO2, 6.9 +/- 0.1 kPa; forced expiratory volume in 1 s, 0.6 +/- 0.07 litre (27 +/- 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain Natriuretic Peptide and atrial Natriuretic Peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 +/- 4.1 pmol/l and 45.0 +/- 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 +/- 0.8 pmol/l and 8.0 +/- 3.5 pmol/l, respectively). Thus, plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain Natriuretic Peptide and the arterial partial pressure of O2 (r = -0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial Natriuretic Peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain Natriuretic Peptide or atrial Natriuretic Peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
J H Winter - One of the best experts on this subject based on the ideXlab platform.
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elevated levels of brain Natriuretic Peptide in acute hypoxaemic chronic obstructive pulmonary disease
Clinical Science, 1992Co-Authors: Chim C. Lang, Paul D Dhillon, W. J. Coutie, Allan D. Struthers, J H WinterAbstract:1. Studies in vitro have recently shown that both atrial Natriuretic Peptide and brain Natriuretic Peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain Natriuretic Peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O 2 , 6.2 ± 0.4 kPa; arterial partial pressure of CO 2 , 6.9 ± 0.1 kPa; forced expiratory volume in 1 s, 0.6 ± 0.07 litre (27 ± 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain Natriuretic Peptide and atrial Natriuretic Peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 ± 4.1 pmol/l and 45.0 ± 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 ± 0.8 pmol/l and 8.0 ± 3.5 pmol/l, respectively). Thus, plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain Natriuretic Peptide and the arterial partial pressure of O 2 ( r = −0.65, r 2 = 0.42, P = 0.03), but not between the plasma atrial Natriuretic Peptide level and the arterial partial pressure of O 2 ( r 2 = 0.07, not significant). The arterial partial pressure of CO 2 did not correlate with the plasma level of either brain Natriuretic Peptide or atrial Natriuretic Peptide. 4. Thus, plasma levels of brain Natriuretic Peptide were proportionately higher than those of atrial Natriuretic Peptide in patients with hypoxaemic chronic obstructive pulmonary disease. Unlike those of atrial Natriuretic Peptide, plasma levels of brain Natriuretic Peptide were correlated with the degree of hypoxaemia. Further studies are required to investigate the release and clearance of brain Natriuretic Peptide in chronic obstructive pulmonary disease, as well as its pulmonary vasodilator activity in vivo.
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elevated levels of brain Natriuretic Peptide in acute hypoxaemic chronic obstructive pulmonary disease
Clinical Science, 1992Co-Authors: Chim C. Lang, Paul D Dhillon, J H Winter, W. J. Coutie, Allan D. Struthers, Brian J LipworthAbstract:1. Studies in vitro have recently shown that both atrial Natriuretic Peptide and brain Natriuretic Peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain Natriuretic Peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 +/- 0.4 kPa; arterial partial pressure of CO2, 6.9 +/- 0.1 kPa; forced expiratory volume in 1 s, 0.6 +/- 0.07 litre (27 +/- 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain Natriuretic Peptide and atrial Natriuretic Peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 +/- 4.1 pmol/l and 45.0 +/- 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 +/- 0.8 pmol/l and 8.0 +/- 3.5 pmol/l, respectively). Thus, plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain Natriuretic Peptide and the arterial partial pressure of O2 (r = -0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial Natriuretic Peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain Natriuretic Peptide or atrial Natriuretic Peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Chim C. Lang - One of the best experts on this subject based on the ideXlab platform.
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elevated levels of brain Natriuretic Peptide in acute hypoxaemic chronic obstructive pulmonary disease
Clinical Science, 1992Co-Authors: Chim C. Lang, Paul D Dhillon, W. J. Coutie, Allan D. Struthers, J H WinterAbstract:1. Studies in vitro have recently shown that both atrial Natriuretic Peptide and brain Natriuretic Peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain Natriuretic Peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O 2 , 6.2 ± 0.4 kPa; arterial partial pressure of CO 2 , 6.9 ± 0.1 kPa; forced expiratory volume in 1 s, 0.6 ± 0.07 litre (27 ± 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain Natriuretic Peptide and atrial Natriuretic Peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 ± 4.1 pmol/l and 45.0 ± 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 ± 0.8 pmol/l and 8.0 ± 3.5 pmol/l, respectively). Thus, plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain Natriuretic Peptide and the arterial partial pressure of O 2 ( r = −0.65, r 2 = 0.42, P = 0.03), but not between the plasma atrial Natriuretic Peptide level and the arterial partial pressure of O 2 ( r 2 = 0.07, not significant). The arterial partial pressure of CO 2 did not correlate with the plasma level of either brain Natriuretic Peptide or atrial Natriuretic Peptide. 4. Thus, plasma levels of brain Natriuretic Peptide were proportionately higher than those of atrial Natriuretic Peptide in patients with hypoxaemic chronic obstructive pulmonary disease. Unlike those of atrial Natriuretic Peptide, plasma levels of brain Natriuretic Peptide were correlated with the degree of hypoxaemia. Further studies are required to investigate the release and clearance of brain Natriuretic Peptide in chronic obstructive pulmonary disease, as well as its pulmonary vasodilator activity in vivo.
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elevated levels of brain Natriuretic Peptide in acute hypoxaemic chronic obstructive pulmonary disease
Clinical Science, 1992Co-Authors: Chim C. Lang, Paul D Dhillon, J H Winter, W. J. Coutie, Allan D. Struthers, Brian J LipworthAbstract:1. Studies in vitro have recently shown that both atrial Natriuretic Peptide and brain Natriuretic Peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain Natriuretic Peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 +/- 0.4 kPa; arterial partial pressure of CO2, 6.9 +/- 0.1 kPa; forced expiratory volume in 1 s, 0.6 +/- 0.07 litre (27 +/- 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain Natriuretic Peptide and atrial Natriuretic Peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 +/- 4.1 pmol/l and 45.0 +/- 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 +/- 0.8 pmol/l and 8.0 +/- 3.5 pmol/l, respectively). Thus, plasma levels of brain Natriuretic Peptide and atrial Natriuretic Peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain Natriuretic Peptide and the arterial partial pressure of O2 (r = -0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial Natriuretic Peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain Natriuretic Peptide or atrial Natriuretic Peptide.(ABSTRACT TRUNCATED AT 250 WORDS)