natriuretic-peptide--c-type and Chronic-Disease

Acute kidney injury (AKI) refers to a sudden decline in renal function. A growing body of evidence demonstrates that AKI is a risk factor for the future development or accelerated progression of chronic kidney disease (CKD), whereas the actual distinction between AKI and CKD remains unknown. CNP is predominantly present in the kidney and possesses multiple renoprotective properties. Urinary CNP excretion tends to be high in AKI, whereas back to the baseline in CKD. The dynamic changes in urinary CNP excretion may help detect underlying renal injury and remodeling both acutely and chronically.

Topics: Acute Kidney Injury; Biomarkers; Chronic Disease; Creatinine; Cystatin C; Glomerular Filtration Rate; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-18; Lipocalin-2; Natriuretic Peptide, C-Type; Proportional Hazards Models

Natriuretic peptides (NPs) secreted by the heart in response to volume overload are pleiotropic molecules with vasodilating, diuretic, natriuretic, antiproliferative, and antifibrotic actions. Functioning of the NP system is altered in congestive heart failure (CHF), suggesting that support of the NP system might be beneficial in treatment of acute and chronic CHF. Several approaches alone or in combination with other pharmacologic therapies have been shown to enhance function of the NP system: direct administration of native and designer NPs, inhibition of degradation of NPs and their second messenger (cyclic guanosine monophosphate ), and stimulation of cGMP generation. Despite increasing numbers of studies using NPs in therapy of acute and chronic CHF, several controversies regarding safety, efficacy, and dosing of NPs need to be addressed. Moreover, further research is warranted to identify the stages and etiologies of CHF that may profit from NP therapy.

Topics: Acute Disease; Chronic Disease; Cyclic GMP; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Prognosis; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Heart failure (HF) is a disease of neurohumoral dysfunction and current pharmacological therapies for HF have not improved mortality rates, thus requiring additional new strategies. Waon therapy for HF patients may be a complementary strategy with peripheral vasodilation via nitric oxide. We hypothesized that Waon therapy would improve neurohumoral factors, such as natriuretic peptides (NP) and the renin-angiotensin-aldosterone system (RAAS) in HF.Methods and Results:Plasma samples were collected from patients enrolled in the WAON-CHF Study (Waon therapy (n=77) or control (n=73)) before and after the treatment. B-type NP (BNP), C-type NP (CNP), and aldosterone (Aldo) levels were measured by respective specific radioimmunoassays. Although clinical parameters significantly improved in the Waon group compared with the control group, BNP, Aldo, and CNP levels were not statistically different between groups. On subanalysis with patient variables, BNP levels were improved in the Waon group treated with angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker or spironolactone. In addition, Aldo levels were improved in the Waon group patients with diabetes mellitus, hypertension, and inotrope use, and CNP levels were improved in Waon group patients with estimated glomerular filtration rate <60 mL/min/1.73 m. Waon therapy may accelerate the favorable actions of RAAS modulators in HF. (WAON-CHF Study: UMIN000006705).

Topics: Aldosterone; Case-Control Studies; Chronic Disease; Complementary Therapies; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Renin-Angiotensin System

C-type natriuretic peptide (CNP) is structurally related to cardiac natriuretic peptides and is currently considered as an endothelium-derived hyperpolarizing factor. Endothelial dysfunction, commonly observed in chronic heart failure (HF) patients is positively affected by physical training.. To evaluate the effect of aerobic physical training on the expression of CNP, 90 HF patients on optimal pharmacological treatment (age 62+/-2 years, mean+/-SEM), randomly assigned in a 3 : 1 ratio to either control group (C, 19 patients) or home-based aerobic exercise-training program group (T, 71 patients), completed the protocol. Plasma assay of CNP, brain natriuretic peptide or B-type natriuretic peptide (BNP), and norepinephrine; echocardiogram; and cardiopulmonary-stress test were performed in all patients at enrollment and after 9 months.. At baseline, in both groups, CNP plasma level was significantly related to BNP (R=0.50), ejection fraction (R=0.43), and peak oxygen uptake (VO2, R=0.43, all P<0.001). After 9 months, trained patients showed an improvement in peak VO2 (P<0.001) and ejection fraction (P<0.05), whereas norepinephrine (P<0.05), BNP (P<0.001), and CNP (P<0.001) decreased. No changes occurred in group C. In group T, the decrease in CNP was significantly related to the increase in peak VO2 (R=0.31, P<0.01), and the relation between CNP and BNP was preserved at the end of the program (R=0.41, P<0.001).. Clinical and functional improvement after physical training in HF patients is associated with a decrease in adrenergic activation and in both CNP and BNP concentration. Changes in CNP plasma concentration after physical training might reflect an improvement in endothelial function.

Topics: Biomarkers; Cardiovascular Agents; Chronic Disease; Down-Regulation; Echocardiography; Exercise Test; Exercise Therapy; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Norepinephrine; Oxygen Consumption; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

C-type natriuretic peptide (CNP) is a vasodilator produced by the vascular endothelium. It shares structural and physiological properties with the cardiac hormones atrial natriuretic peptide and brain natriuretic peptide (BNP), but little is known about its pathophysiological role in chronic heart failure (CHF). We assessed the hypothesis that CNP is produced by the heart in patients with CHF.. Myocardial CNP production was determined (difference in plasma levels between the aortic root and coronary sinus [CS]) in 9 patients undergoing right and left heart catheterization as part of their CHF assessment (all male, age 59+/-9 years; New York Heart Association class 2.2+/-0.1; left ventricular ejection fraction 29+/-5%; creatinine 105+/-8 micro mol/L [all values mean+/-SEM]). BNP, established as originating from myocardium, was assessed from the same samples as a positive control. Analyses were performed by a blinded operator using a standard competitive radioimmunoassay kit (Peninsula Laboratories, Bachem Ltd UK). A step-up (29%) in plasma CNP concentration was found from the aorta to the CS (3.55+/-1.53 versus 4.59+/-1.54 pg/mL, respectively; P=0.035). The mean increase in CNP was 0.90+/-0.35 pg/mL (range 0.05 to 2.80 pg/mL). BNP levels increased by 57% from aorta to CS (86.0+/-20.5 versus 135.0+/-42.2 pg/mL; P=0.01). CS CNP levels correlated with mean pulmonary capillary wedge pressure (r=0.82, P=0.007).. We have shown that CNP is produced by the heart in patients with CHF. Although further evaluation is required to define its full pathophysiological role in this condition, CNP may represent an important new local mediator in the heart.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiac Catheterization; Chronic Disease; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Dysfunction, Left

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial natriuretic peptide (ANP). Although it has been suggested that CNP is released from the endothelium for the regulation of local vascular tone, no data are available concerning the vasodilatory response to CNP in humans.. Strain-gauge plethysmography was used to determine the vasodilatory effects of intra-arterially infused CNP compared with the effects of ANP infusion in 11 patients with chronic heart failure (CHF) and 11 age-matched healthy controls. Graded doses of CNP and ANP (8, 16, 32, and 48 pmol.min-1.dL-1 tissue volume) were administered randomly into the nondominant brachial artery, and forearm blood flow (FBF) was measured. No significant changes in systemic blood pressure and heart rate were found during the study. Both the absolute and percent FBF responses to ANP relative to the baseline value were significantly lower in CHF patients than in healthy controls (P < .01), whereas the responses to CNP were similar. The calculated forearm spillover of cyclic GMP (cGMP) was significantly lower in CHF patients receiving the highest dose of ANP (P < .02), whereas changes in cGMP spillover after the equimolar dose of CNP were significantly higher (P < .02), despite the lesser potency of CNP.. In patients with CHF the peripheral vasodilatory effect of ANP is attenuated, but CNP-induced peripheral vasorelaxation is preserved, with CNP being less potent for equimolar doses.

Topics: Atrial Natriuretic Factor; Blood Vessels; Cardiac Output, Low; Chronic Disease; Cyclic GMP; Female; Forearm; Humans; Injections, Intra-Arterial; Male; Middle Aged; Natriuretic Peptide, C-Type; Plethysmography; Proteins; Regional Blood Flow; Vascular Resistance; Vasodilation

The aim of this study was to evaluate the transcriptomic profiling of C-type natriuretic peptide (CNP) and of its specific receptor, NPR-B in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C). mRNA expression was evaluated by Real-Time PCR and total RNA was extracted from leukocytes of C (n=8) and of HF patients (NYHA I-II, n=7; NYHA III-IV, n=13) with PAXgene Blood RNA Kit. Significantly higher levels of CNP mRNA expression were found in HF patients as a function of clinical severity (C=0.23±0.058, NYHA I-II=0.47±0.18, NYHA III-IV=2.58±0.71, p=0.005 C vs NYHA III-IV, p=0.017 NYHA I-II vs NYHA III-IV) and NPR-B transcript levels resulted down-regulated in HF patients with higher NYHA class (C=2.2±0.61, NYHA I-II=2.76±0.46, NYHA III-IV=0.29±0.13, p=0.001 C vs NYHA III-IV, p<0.0001 NYHA I-II vs NYHA III-IV). A significant negative correlation between CNP and NPR-B mRNA expression (r=0.5, p=0.03) was also observed. These results suggest a co-regulation of NPR-B and CNP expression supporting the relevance of this receptor in human disease characterized by a marked inflammatory/immune component and suggesting the possibility of manipulating inflammation via pharmacological agents selective for this receptor.

Topics: Adult; Chronic Disease; Female; Gene Expression Profiling; Heart Failure; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Natriuretic Peptide, C-Type; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Severity of Illness Index

CNP (C-type natriuretic peptide) is a vasodilatory peptide produced by vascular endothelium and the human heart with a short half-life. CNP has been identified within the human kidney; however, few results are available on whether the human kidney is a systemic source of CNP. The aim of the present study was to establish whether CNP is secreted by the human kidney and if synthesis is blunted in CHF (chronic heart failure). A total of 20 male subjects (age, 57+/-2 years; mean+/-S.E.M.) undergoing CHF assessment (n=13) or investigation of paroxysmal supraventricular arrhythmia (normal left ventricular function in sinus rhythm during procedure) (n=7) were recruited. Renal CNP production was determined from concomitant plasma concentrations in the aorta and renal vein. When considering all subjects, a significant step-up in plasma CNP was found from the aorta to renal vein (3.0+/-0.3 compared with 8.3+/-2.4 pg/ml respectively; P=0.0045). The mean increase in CNP was 5.3+/-2.4 pg/ml (range, -0.9 to +45.3 pg/ml). In patients with CHF, the aortic concentration was 3.3+/-0.4 pg/ml compared with a renal vein concentration of 4.3+/-0.6 pg/ml (P=0.11). In those with normal left ventricular function, the respective values were 2.5+/-0.5 and 15.7+/-6.0 pg/ml (P=0.01). In conclusion, CNP is synthesized and secreted into the circulation by the normal human kidney, where it may have paracrine actions. Net renal secretion of CNP appears to be blunted in patients with CHF.

Topics: Aged; Aorta; Atrial Fibrillation; Chronic Disease; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, C-Type; Renal Veins; Ventricular Function, Left

C-type natriuretic peptide (CNP) significantly increases in chronic heart failure (CHF) patients as a function of clinical severity. Aim of this study was to evaluate in CHF patients the relationship between circulating CNP concentrations and echo-Doppler conventional indices of left ventricular (LV) function as well as less load independent parameters as dP/dt. LV ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) and LV dP/dt were evaluated together with plasma CNP levels in 38 patients with CHF and in 63 controls. CNP levels resulted significantly higher in CHF patients than in controls (7.19+/-0.59 pg/ml vs. 2.52+/-0.12 pg/ml, p<0.0001). A significant correlation between dP/dt and CNP levels (r=-0.61, p<0.0001) was observed. A good correlation with EF (r=-0.55, p<0.001) and a less significant relation with LVEDD (r=0.316, p<0.05) were also reported. When patients were divided according to dP/dt values a very significant difference in CNP levels was observed: Group I (<600, n=25) vs. Group II (>600, n=13): 8.46+/-0.69 and 4.75+/-0.75 pg/ml, respectively, p<0.001. This is the first study that reports a correlation between CNP and dP/dt in CHF patients, thus suggesting a possible role on cardiac contractility.

Topics: Chronic Disease; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Predictive Value of Tests; Reproducibility of Results; Severity of Illness Index; Ventricular Dysfunction, Left

Topics: Adult; Aged; Chronic Disease; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Plasma; Protein Precursors; Radioimmunoassay

We measured plasma concentrations of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively) and endothelin-1 in 20 patients with chronic respiratory diseases (CRD) to establish whether these peptides are increased in patient groups with CRD (group A, PaO2 > or = 60 mm Hg; group B, PaO2 < 60 mm Hg) and whether a correlation exists between the levels of natriuretic peptides or endothelin-1, and blood gas variables. In patients receiving long-term oxygen therapy (LTOT), plasma ANP, BNP, and endothelin-1 were compared before and after LTOT. We compared the levels of plasma ANP, BNP, and endothelin-1 in the presence or absence of right heart overloading (RHO) found in the ECG. Plasma ANP and BNP levels in group B patients were higher than those in group A and control subjects, and endothelin-1 in group B patients was higher than in control subjects. Inverse correlations were found between PaO2 and levels of plasma ANP, BNP, and endothelin-1. Plasma ANP, BNP, and endothelin-1 decreased significantly 25.4 days after LTOT. In 10 patients with RHO findings in the ECG, plasma ANP and BNP levels were significantly elevated compared with those in patients without RHO. These findings show that plasma ANP, BNP, and endothelin-1 are elevated according to the degree of hypoxemia, and they suggest that decreases in plasma ANP, BNP, and endothelin-1 may be used as indexes of the improvement by LTOT, and that plasma ANP and BNP may represent markers of RHO.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chronic Disease; Electrocardiography; Endothelins; Female; Heart; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Oxygen; Oxygen Inhalation Therapy; Proteins; Respiratory Tract Diseases