Atrial Natriuretic Peptides, Right Atrial Infarction and Prognosis of Patients with Myocardial Infarction—A Single-Center Study

Atrial natriuretic peptide (ANP) is secreted in response to the stretching of the atrial wall. Atrial ischemia most likely impairs the ability of atrial myocytes to produce ANP. Atrial infarction (AI) is rarely diagnosed but not infrequently associated with myocardial infarction (MI). The aim of the study was to assess the association between AI and the prognostic value of N-terminal proANP (NT-proANP) in patients with MI treated with primary percutaneous coronary intervention (PCI). We evaluated data of 100 consecutive patients. Plasma levels of NT-proANP were measured by the ELISA method. ECG recordings were interpreted to diagnose AI according to Liu’s criteria. All patients were followed-up prospectively for 12 months for the manifestation of major adverse cardiovascular events (MACE), defined as unplanned coronary revascularization, stroke, reinfarction or all-cause death. AI was diagnosed in 36 patients. 14% of patients developed MACE. AI did not affect the incidence of MACE or any of its components, nor the patients’ prognosis. NT-proANP revealed to be a strong predictor of death but was not associated with other adverse events. Conclusions: AI in patients with MI treated with primary PCI is not connected with their prognosis nor affects the usefulness of NT-proANP in predicting death during the 12-month follow-up.

Secretion of Atrial Natriuretic Peptide (Anp), Heart Reconditioning and Remolding in Elite Endurance Trained Athletes

Aim / Objective: The aim of this study was to evaluate the effect of maximal exercise on the level of cardiac remolding and Atrial Natriuretic Peptide (ANP) in elite athletes as compared to sedentary healthy subjects and correlation of ANP with the adaptation of athlete’s heart and cardiac remodeling (if any) Place and Duration of Study: The present study was carried out at the Department of Physiology, Army Medical College, with collaboration of Armed Forces Institute of Cardiology (AFIC) Rawalpindi from June 2003 to May 2004. Methodology: A total number of 44 subjects were included in this study. These comprised of 22 elite endurance athletes and 22 healthy sedentary volunteers as controls. All subjects were examined clinically to rule out the cardiovascular and pulmonary diseases on the basis of medical history, physical examination, and echocardiography. All the selected subjects were examined on a Toshiba Power Vision 6000 echocardiograph for assessing and measuring their LV end-diastolic internal diameter (LVIDd), Diastolic interventricular septal thickness (IVSTd), diastolic posterior wall thickness (PWTd). The left ventricular mass was (LVM) was calculated by using the Devereux formula. They were subject to go for ergometer cycle exercise before breakfast. The Blood samples were drawn before and after exercise to assess the level of ANP in their samples. Results: It was found that LVIDd, IVSTd, PWTd, LVM were higher in athletes as compared to their age, sex and BMI matched controls. The ANP levels in athlete’s plasma were also high in post and pre exercise sample as compared to controls. Conclusion: Systolic blood pressure, Diastolic Blood Pressure and heart rate are lower in endurance elite athletes than matched sedentary controls. The maximal Exercise increases the level of Atrial Natriuretic Peptide (ANP) in elite athletes significantly as compared to sedentary healthy controls. There was a Positive correlations between ANP and LVIDd, IVSTd, PWTd, and LVM while there was negative correlation between ANP and heart rate, ANP and Blood pressure. However, none of correlation was found to be statistically significant. Keywords: Athlete’s Heart, ANP, Cardiac remodeling in athletes, Echocardiography of heart

Inhibition of endogenous ouabain by atrial natriuretic peptide is a guanylyl cyclase independent effect

Background Endogenous ouabain (EO) and atrial natriuretic peptide (ANP) are important in regulation of sodium and fluid balance. There is indirect evidence that ANP may be involved in the regulation of endogenous cardenolides. Methods H295R are human adrenocortical cells known to release EO. Cells were treated with ANP at physiologic concentrations or vehicle (0.1% DMSO), with or without guanylyl cyclase inhibitor 1,2,4 oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cyclic guanosine monophosphate (cGMP), the intracellular second messenger of ANP, was measured by a chemiluminescent immunoassay and EO was measured by radioimmunoassay of C18 extracted samples. Results EO secretion is inhibited by ANP treatment, with the most prolonged inhibition (90 min vs ≤ 60 min) occurring at physiologic ANP concentrations (50 pg/mL). Inhibition of guanylyl cyclase with ODQ, also reduces EO secretion. The inhibitory effects on EO release in response to cotreatment with ANP and ODQ appeared to be additive. Conclusions ANP inhibits basal EO secretion, and it is unlikely that this is mediated through ANP-A or ANP-B receptors (the most common natriuretic peptide receptors) or their cGMP second messenger; the underlying mechanisms involved are not revealed in the current studies. The role of ANP in the control of EO synthesis and secretion in vivo requires further investigation.

Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide

Background Atrial natriuretic peptide (ANP) is a cardiovascular and metabolic hormone that has been identified recently as being associated with chronic kidney disease (CKD) without diabetes. Cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin (ADP) contribute to the development of type 2 diabetes (T2DM). The aim here was to investigate the relationships of ANP with cytokine levels and clinical variables in T2DM nephropathy patients. Methods A total of 81 participants with T2DM were recruited, including 37 patients with normoalbuminuria, 23 patients with microalbuminuria and 21 patients with macroalbuminuria. Serum concentrations of ANP and cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANP and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANP and the severity and presence of albuminuria. Results The macroalbuminuria patients exhibited higher plasma levels of ANP, TNF-α, IL-6, and ADP; higher serum creatinine (Cr) and blood urea nitrogen (BUN); and longer duration of diabetes mellitus (DM) than the patients with normoalbuminuria and microalbuminuria. Plasma ANP level was significantly associated with TNF-α (r = 0.876, p < 0.001), IL-6 (r = 0.816, p < 0.001) and ADP (r = 0.772, p < 0.001), independent of the duration of DM or the BUN concentration. Conclusion ANP is higher in type 2 diabetes mellitus nephropathy subjects, especially those who have macroalbuminuria, which is associated with compensatory responses to inflammation.

First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension

M-atrial natriuretic peptide (MANP) is a novel ANP (atrial natriuretic peptide) analog engineered to be an innovative particulate GC-A (guanylyl cyclase A) receptor activator. The rationale for its design was to develop a best-in-class GC-A activator with enhanced cGMP activating, natriuretic, aldosterone-suppressing, and blood pressure–lowering actions, compared with endogenous ANP, for the treatment of hypertension. Here, we report the first-in-human study on the safety, tolerability, neurohumoral, renal, and blood pressure–lowering properties of MANP in hypertension subjects. This was an open-label sequential single ascending dose design in which all subjects stopped all antihypertensive agents for 14 days before receiving a single subcutaneous injection of MANP. MANP was safe, well tolerated, activated cGMP, induced natriuresis, reduced aldosterone, and decreased blood pressure at or below the maximal tolerated dose. Thus, MANP has a favorable safety profile and produced expected pharmacological effects in human hypertension. Our results support further investigations of MANP as a potential future blood pressure–lowering, natriuretic and aldosterone-suppressing drug for hypertension especially resistant hypertension.