ANP Concentrations Research Articles

Abstract 058: Transforming Growth Factor β1 Antagonizes Npr1 Expression and Vascular Signaling: Role of Transcription Factor δEF1 Transforming Growth Factor β1 Antagonizes Npr1 Expression and Vascular Signaling: Role of Transcription Factor δEF1

The objective of the present study was to examine the repressive effect of transforming growth factor beta 1 (TGF-β1) in the regulation of Npr1 (coding for guanylyl cyclase/natriuretic peptide receptor-A; GC-A/NPRA) gene expression and vascular signaling. The rat thoracic aortic vascular smooth muscle cells (RTASMC) and denuded aortic rings were cultured in Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum and treated with TGF-β1 in a time-and dose-dependent manner. Treatment with TGF-β1 decreased NPRA mRNA and protein levels by 62% (0.42 ± 0.05 vs. control, 0.9 ± 0.02, p < 0.01) and 55% (9603 ± 860 vs. control, 22211 ± 1449, p < 0.01), respectively. TGF-β1 treatment significantly increased delta EF1 (δEF1) protein expression by 2.4-fold (907.9 ± 36.5. vs. control, 378.5 ± 10.3; p < 0.001) and enhanced its recruitment to Npr1 promoter. TGF-β1-treated RTASMCs and denuded aortic rings showed significant increases in α-smooth muscle actin (α-SMA) and collagen type 1 alpha 2 (COL1A2) protein expression, which were markedly attenuated by ANP treatments. The TGF-β1-pretreated cells showed 2.6-fold increase in α-SMA (control, 1523 ± 143, TGF-β1, 3997 ± 182 and TGF-β1 + ANP, 2172 ± 135) and 3.4-fold increase in COL1A2 (control, 1250 ± 77, TGF-β1, 4234 ± 110 and TGF-β1 + ANP, 1546 ± 57), respectively. In ex vivo experiments of denuded-aortic rings, TGF-β1 decreased Npr1 mRNA and protein levels by 62% (0.39 ± 0.06 vs. control 1.10 ± 0.01) and 70% (2609 ± 69 vs. control 5775 ± 123), respectively, and significantly (p < 0.0) increased the expression of TGF-β1-responsive proteins, namely α-SMA (2.6-fold) and COL1A2 (3.1-fold). Treatment with increasing concentrations of ANP (IC50=6x10 -9 M), relaxed denuded aortic rings contracted with prostaglandin F2α (PGF2α); however, pretreatment with TGF-β1 significantly attenuated ANP-mediated vascular relaxation after PFG2α contraction (ANP-treated, 68.68 ± 9.4 vs. TGF-β1 + ANP-treated 88.85 ± 4.7). The endothelium-intact vessels were not affected by TGF-β1 incubation. Together, the present results suggest that an antagonistic cascade exists between TGF-β1 pathways and ANP/NPRA signaling, which might be critical in the vascular remodeling and regulation of hypertension and cardiovascular homeostasis.

Changes of adrenomedullin and natriuretic peptides in patients with adrenal medullary hyperplasia prior to and following pharmacological therapy and adrenalectomy.

The aim of the present study was to investigate the pathophysiological functions of adrenomedullin (ADM), atrial and brain natriuretic peptides (ANP and BNP) in patients with adrenal medullary hyperplasia (AMH). Plasma ADM, ANP and BNP concentrations were measured in 20 patients with AMH, 35 patients with essential hypertension (EH), and 40 healthy control subjects. Following effective antihypertensive therapy, the values in AMH and EH patients were measured again and laparoscopic adrenalectomy was performed for AMH patients. At 2 weeks after surgery, the three peptides were measured again. The AMH patients had higher plasma concentrations of ADM, ANP and BNP compared with the EH and control subjects. There were significant differences in the values of ADM, ANP and BNP between adrenal vein and inferior vena cava and between AMH and contralateral adrenal vein. Plasma ADM concentration was correlated with serum epinephrine and norepinephrine and urine vanillylmandelic acid, in addition to systolic and diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and ANP and BNP values in the AMH group. Following antihypertensive treatment, ADM, ANP and BNP were significantly decreased in EH patients, but remained unchanged in AMH subjects. However, these concentrations significantly decreased following surgery. Therefore, the present results suggest that ADM, ANP and BNP may be involved in regulating adrenal medulla functions.

Prognostic Value of Adrenomedullin and Natriuretic Peptides in Uroseptic Patients Induced by Ureteroscopy

The aim of this paper is to investigate whether urosepsis is related to irrigation pressure of ureteroscopy (URS) and evaluate the prognostic value of adrenomedullin (ADM) and atrial and brain natriuretic peptides (ANP and BNP) in URS-induced uroseptic patients. From July 2008 to October 2013, we enrolled 332 patients with untreated unilateral ureteral obstruction (UUO). The UUO group included three subgroups of, respectively, 118, 132, and 82 patients who underwent URS under intermittent stable irrigation pressure of, respectively, 80, 120, and 160 mmHg. The plasma concentrations of ADM, ANP, and BNP were measured in all subjects. URS was performed for all UUO patients; the values of the three peptides were measured again after URS. Irrigation pressure and stone size were independent risk factors of urosepsis. After URS, the plasma concentrations of ADM, ANP, and BNP were significantly higher in uroseptic patients. Moreover, the concentrations were significantly higher depending on the disease severity. Plasma concentrations of the three peptides were correlated with plasma ET concentration in the uroseptic patients. The areas under receiver operating characteristic (ROC) curve of ADM, ANP, and BNP for predicting urosepsis were 0.811, 0.728, and 0.764, respectively. In conclusion, ADM, along with ANP and BNP, is valuable for prognosis in urosepsis secondary to URS which is associated with irrigation pressure.

Relationship between Adiponectin Gene Polymorphisms and Late-Onset Alzheimer's Disease.

In recent years, researchers have found that adiponectin (ANP) plays an important role in the pathogenesis of Alzheimer's disease (AD), and low serum concentrations of ANP are associated with AD. Higher plasma ANP level have a protective effect against the development of cognitive decline, suggesting that ANP may affect AD onset. Meanwhile, accumulating evidence supports the crucial role of ANP in the pathogenesis of AD. To study the relationship between ANP gene polymorphisms (rs266729, -11377C>G and rs1501299, G276T) and late-onset AD (LOAD), we carried out a case-control study that included 201 LOAD patients and 257 healthy control subjects. Statistically significant differences were detected in the genotype and allelotype frequency distributions of rs266729 and rs1501299 between the LOAD group and the control group, with a noticeable increase in the G and T allelotype frequency distributions in the LOAD group (P < 0.05). Logistic regression analysis using recessive model and additive model revealed that the rs266729 GG and rs1501299 TT genotypes are associated with a greater risk of LOAD. Haplotype analysis identified four haplotypes: CG, CT, GG, and GT. The frequencies of the CT and GG haplotypes were not significantly different (P > 0.05) between the LOAD group and control group, whereas the CG and GT haplotypes were significantly different (P < 0.05), suggesting a negative correlation between the CG haplotype and LOAD onset (OR = 0.74, 95% CI = 0.57–0.96, P = 0.022), and a positive correlation between the GT haplotype and LOAD onset (OR = 2.29, 95% CI = 1.42–3.68, P = 0.005). Therefore, we speculated that the rs266729 and rs1501299 of ANP gene polymorphisms and the GT and CG haplotypes were associated with LOAD.

Plasma concentrations of adrenomedullin and natriuretic peptides in patients with essential hypertension.

This study was designed to assess any changes in the plasma concentrations of adrenomedullin (ADM) and atrial and brain natriuretic peptide (ANP and BNP, respectively), and to investigate their pathophysiological roles in patients with essential hypertension (EH). The plasma ADM, ANP and BNP concentrations were measured in 64 patients with untreated EH and 35 normotensive control subjects. After 4 weeks of effective antihypertensive therapy with oral drugs for the hypertensive patients, the plasma concentrations of ADM, ANP and BNP in the hypertensive patients were measured again. The plasma concentrations of ADM, ANP and BNP were significantly higher in the hypertensive patients than those in the control subjects, and the concentrations increased with the clinical stage. Furthermore, the hypertensive patients exhibited increased mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr) and decreased glomerular filtration rates (GFRs) compared with the control subjects. The plasma ADM concentration was not only correlated with BUN, Scr and the GFR, but was also associated with the MAP and the plasma levels of ANP and BNP. Following effective antihypertensive therapy with oral medication for 4 weeks, the plasma concentrations of ADM, ANP and BNP were significantly, but not sharply, decreased. In conclusion, ADM, along with ANP and BNP, may be involved in the mechanisms acting against a further increase in blood pressure and may be useful biomarkers for the diagnosis and treatment of hypertensive patients.

Statin therapy and bone marrow CD34 + cell frequency in type 2 diabetes mellitus: A cross-sectional study

monitoring of AF recurrence by means of dual-chamber pacemaker diagnostic functions. All measurements of biomarkers' levels were performedusing the immunoenzymatic ELISAmethod,which is associated with less limitations compared to radioimmunologic assay used in most other studies [5]. The limitation of the study, however, was the small number of patients with no AF recurrence after CV, and the lack of LV diastolic function assessment. Almost 70% of patients were treated with ACEI or ARBs, which might have affected neurohumoral factors' levels. In conclusion, BNP level is increased in patients with preserved LV systolic function and persistent AF. Sinus rhythm restoration results in a significant decrease of BNP concentration; however an increased BNP level on the 7th day after CV of ≥700 fmol/ml is an independent predictor of AF recurrence. This observation could be of importance in patientswith persistent AF inwhom there is no clear decision considering the choice of further strategy of AF treatment: rhythm control or rate control. Neither baseline ANP, ALD, or ET-1 concentration, nor their changes within 7 days after conversion to sinus rhythm have prognostic value to predict AF relapse during 12-month observation.

Incomplete recovery of mechanical and endocrine left atrial functions one month after electrical cardioversion for persistent atrial fibrillation: a pilot study

BackgroundRestoration of the mechanical and endocrine functions of the left atrium remains controversial after electrical cardioversion treatment for persistent atrial fibrillation. The objective of the prospective study was to describe the recovery of the endocrine and mechanical functions of the left atrium.MethodsEvaluation of left atrium recovery after electrical cardioversion by the new speckle-tracking echocardiography technique and proANP measurement.ResultsTwenty patients suffering from persistent atrial fibrillation with no alteration of left ventricular ejection fraction were prospectively evaluated at baseline and then one month later by echocardiography, measuring left atrial volume and left atrial deformation (MPALS), as well as the proANP and BNP concentrations. One month after cardioversion 10 patients remained in sinus rhythm and 10 showed recurrent atrial fibrillation. No significant differences between the two groups in terms of clinical, echocardiographic and endocrine parameters were observed at baseline evaluation. We observed a significant reduction of left atrial volume only in the sinus group, whereas restoration of the left atrial deformation was only partial (18%) in that group. By contrast, we registered no significant changes in ANP concentration at one month in either the sinus or the atrial fibrillation groups.ConclusionThese results suggest that restoration of left atrium mechanical function is only partial one month after treatment of persistent atrial fibrillation by electrical cardioversion, whereas a significant reduction of left atrial volume was noted, explaining the remaining high level of ANP in the sinus group.

Angiotensin AT2 receptor agonist stimulates high stretch induced- ANP secretion via PI3K/NO/sGC/PKG/pathway

Angiotensin II (Ang II) type 1 receptor (AT1R) mediates the major cardiovascular effects of Ang II. However, the effects mediated via AT2R are still controversial. The aim of the present study is to define the effect of AT2R agonist CGP42112A (CGP) on high stretch-induced ANP secretion and its mechanism using in vitro and in vivo experiments. CGP (0.01, 0.1 and 1μM) stimulated high stretch-induced ANP secretion and concentration from isolated perfused rat atria. However, atrial contractility and the translocation of extracellular fluid did not change. The augmented effect of CGP (0.1μM) on high stretch-induced ANP secretion was attenuated by the pretreatment with AT2R antagonist or inhibitor for phosphoinositol 3-kinase (PI3K), nitric oxide (NO), soluble guanylyl cyclase (sGC), or protein kinase G (PKG). However, antagonist for AT1R or Mas receptor did not influence CGP-induced ANP secretion. In vivo study, acute infusion of CGP for 10min increased plasma ANP level without blood pressure change. In renal hypertensive rat atria, AT2R mRNA and protein levels were up-regulated and the response of plasma ANP level to CGP infusion in renal hypertensive rats augmented. The pretreatment with AT2R antagonist for 10min followed by CGP infusion attenuated an increased plasma ANP level induced by CGP. However, pretreatment with AT1R or Mas receptor antagonist unaffected CGP-induced increase in plasma ANP level. Therefore, we suggest that AT2R agonist CGP stimulates high stretch-induced ANP secretion through PI3K/NO/sGC/PKG pathway and these effects are augmented in renal hypertensive rats.

Atrial natriuretic peptide and cardiac troponin I concentrations in healthy Warmblood horses and in Warmblood horses with mitral regurgitation at rest and after exercise

ObjectiveAtrial natriuretic peptide (ANP) and cardiac troponin I (cTnI) serve as biomarkers for increased cardiac pressure/volume loading and for myocardial stress or damage. The objective was to describe the time course of plasma ANP concentrations (CpANP) and plasma cTnI concentrations (CpcTnI) in horses with mitral regurgitation (MR) compared to healthy horses at rest and after exercise, and to describe the relationship of CpANP with cardiac dimensions and intracardiac pressures. Animals15 healthy Warmblood horses and 7 Warmblood horses with MR. MethodsCardiac dimensions at rest were measured using echocardiography. All horses underwent standardized treadmill exercise. Biomarker concentrations and intracardiac pressures were measured at rest and after exercise. Hypotheses were tested using statistical methods. The level of significance was P < 0.05. ResultsHorses with MR showed increased left atrial (LA) and left ventricular (LV) dimensions but similar exercise capacity compared to healthy horses. Pulmonary capillary wedge pressures (PCWP) and CpANP increased with exercise. Horses with MR had higher PCWP and higher CpANP at rest and after exercise compared to healthy horses, with the maximum difference in CpANP reached 10 min after exercise. CpANP was significantly related to PCWP and – although inconsistently and only in healthy horses – to echocardiographic indices of LA and LV size and function. CpcTnI was low throughout the study in both groups. ConclusionsCpANP is increased in horses with MR and is related to LA pressures and to left heart dimensions. MR is not necessarily associated with exercise intolerance and exercise-induced myocardial stress or damage.

Stimulation of ANP secretion by Angiotensin‐(1–9) via Angiotensin Type 2 Receptor

Renin‐angiotensin system (RAS) plays an essential role in cardiovascular homeostasis. The peptide hormone angiotensin II (Ang II), generated by angiotensin converting enzyme (ACE), mainly regulates cardiovascular system via its receptors. More recently, we have reported that Ang‐(1–7) stimulates ANP secretion via Mas receptor. However, Ang‐(1–9), converted from Ang I by ACE 2, is still unknown. The aim of the present study is to determine whether Ang‐(1–9) stimulates ANP secretion using isolated perfused beating atria and to find out its signaling pathway. Ang‐(1–9) augmented ANP secretion and concentration in a dose‐dependent manner. Ang‐(1–9)‐induced ANP secretion (about 60% increase by 3 uM) was attenuated by the pretreatment with Ang II type 2 receptor (AT2R) antagonist but not by AT1R or Mas receptor antagonist. In addition, pretreatment with inhibitors of phosphatidylinositol 3 kinase(PI3K), protein kinase B (Akt), endothelial nitric oxide synthase (eNOS) or guanylyl cyclase (GC), blocked the attenuation of ANP secretion by Ang‐(1–9). However, Ang‐(1–9) did not influence atrial contractility and ECF translocation. These results suggest that Ang‐(1–9) stimulates ANP secretion via AT2R, PI3K, Akt, eNOs, GC pathway. We try to do further study to find out the signaling mechanism involved these responses.Supported by the National Research Foundation (2012–0009322 )

A crossover comparison of urinary albumin excretion as a new surrogate marker for cardiovascular disease among 4 types of calcium channel blockers

BackgroundAt the intervention for cardiovascular disease (CVD), albuminuria is a new pivotal target. Calcium channel blocker (CCB) is one of the most expected agents. Currently CCBs have been classified by delivery system, half-life and channel types. We tested anti-albuminuric effect among 4 types of CCBs. MethodsSubjects were 50 hypertensives (SBP/DBP 164.7±17.1/92.3±12.2mmHg, s-Cr 0.81±0.37mg/dl, urinary albumin excretion (UAE) 69.4 (33.5–142.6) mg/gCr). Four CCBs were administered in a crossover setting: nifedipine CR, a long biological half-life L type by controlled release; cilnidipine, an N/L type; efonidipine, a T/L type; and amlodipine, a long biological half-life L type. ResultsComparable BP reductions were obtained. UAE at endpoints ware as follows (mg/gCr, *P<0.01): nifedipine CR 30.8 (17.3–81.1),* cilnidipine 33.9 (18.0–67.7),* efonidipine 51.0 (21.2–129.8), amlodipine 40.6 (18.7–94.7). By all agents, significant augmentations were observed in PRA, angiotensin I and angiotensin II (AngII). AngII at cilnidipine was significantly lower than that at amlodipine. PAC at cilnidipine and efonidipine was significantly lower than that at amlodipine. Nifedipine CR significantly reduced ANP concentration. ConclusionsIt is revealed that only nifedipine CR and cilnidipine could reduce albuminuria statistically. Thus, it is suggested that the 2 CCBs might be favorable for organ protection in hypertensives.

Research on Changes on Blood Plasma ANP of Female Boxer during Training

Objective: In order to prepare for the national competition, change on blood plasma ANP of female boxer in training period was tested. Methods: In six weeks preparing for the training period, test blood plasma ANP on Monday morning in the first, third, fifth, seventh weeks respectively. Results: The analysis revealed: (1) The basis ANP was in lower limit of normal values, with in-depth training, ANP increased gradually, and the levels were significant differences (P&lt;0.01); (2) Subjects grouped according to athletic performance , there was positive correlation between plasma ANP concentration and years of specialized training on elite athletes, correlation coefficient was 0.82, but plasma ANP concentration was not relevant with years of specialized training in general athletes. Conclusions: The longer the training period, the more adaptable remodeling made in heart endocrine capacity, and the higher ANP concentration in resting state.

Oxidative stress augments the secretion of atrial natriuretic peptide in isolated rat atria

Reactive oxygen species (ROS) play a role in cardiovascular diseases such as hypertension and heart failure. The objective of the present study was to investigate the role of endogenous ROS in atrial hemodynamics and ANP secretion in isolated perfused beating rat atria. Pyrogallol (a generator of superoxide anion, 0.1, 1mM) or hydrogen peroxide (0.1, 1, 10, 30mM) was perfused into atria paced at 1.2Hz. Pyrogallol and hydrogen peroxide stimulated ANP secretion and concentration in a dose-dependent manner and dramatically decreased atrial contractility and translocation of extracellular fluid. The stimulatory effect of pyrogallol and hydrogen peroxide on ANP secretion was attenuated by the pretreatment with ascorbic acid (an antioxidant; 1mM) and cariporide (an inhibitor of the Na(+)/H(+) exchanger; 1μM) but negative inotropic effect was not changed. U120 (a MAPK(erk) pathway inhibitor; 10μM) attenuated the stimulatory effect of hydrogen peroxide on ANP secretion. However, U120 augmented negative inotropic effect and stimulatory effect of ANP concentration induced by pyrogallol. Antioxidant such as N-acetyl cystein, gallate, propyl gallate, or ellagic acid did not cause any significant changes in atrial parameters. These results suggest that intracellular - formed ROS stimulates ANP secretion partly through activation of MAPK(erk) pathway and Na(+)/H(+) exchanger.

Natriuretic peptide levels in intrauterine growth-restricted fetuses with absent and reversed end-diastolic flow of the umbilical artery in relation to ductus venosus flow velocities

To determine if changes in natriuretic peptide levels [propeptide of atrial natriuretic peptide (proANP) and N-terminal propeptide of brain natriuretic peptide (NT-proBNP)] can be demonstrated in fetuses with serious growth restriction and Doppler ultrasonographic findings of hemodynamic compromise. Natriuretic peptides of the umbilical vein (proANP and NT-proBNP), arterial and venous blood gases, as well as lactate levels of the umbilical vein were determined in 38 appropriate for gestational age (AGA) fetuses, and 24 intrauterine growth-restricted (IUGR) fetuses with absent (zero-flow) and 17 IUGR fetuses with reversed end-diastolic flow (reverse-flow) of the umbilical artery. A continuous increase in natriuretic peptides in the presence of progressive deterioration was shown. ANP concentrations were significantly lower in the AGA group (mean 818 fmol/mL; range 508-991 fmol/mL) than the zero-flow group (mean 19,680 fmol/mL; range 13,680-25,080 fmol/mL) and the reverse-flow group (mean 33,880 fmol/mL; range 24,365-41,786 fmol/mL). Significant differences were further demonstrated in BNP concentrations of the AGA group (mean 32 fmol/L; range 25-38 fmol/L), zero-flow group (mean 1191 fmol/L; range 908-1655 fmol/L), and reverse-flow group (mean 3063 fmol/L; range 1281-4968 fmol/L). Additionally, significant differences in lactate concentrations were observed for the three groups: AGA, 2.6 mmol/L (range 2-3 mmol/L); zero-flow group, 4.1 mmol/L (range 3.3-5 mmol/L); and reverse-flow group, 7.7 mmol/L (range 5.9-13.7 mmol/L). Increased ANP levels correlated with the arterial base excess and lactate concentrations, as well as with the flow velocities in the ductus venosus during atrial contraction (a-wave), and both ductus venosus indices (S-a)/D and (S-a)/V(mean). No correlations were established for BNP. As components of a compensatory mechanism, natriuretic peptides exert an influence on the cardiovascular function of the fetus.

Renal Actions of Neutral Endopeptidase Inhibition in Rats with Chronic Heart Failure

Problem statement: We aim to evaluate the effects of acute and chronic inhibition of Neutral EndoPeptidase (NEP), by ONO-9902, on plasma and renal NEP gene expression, hemodynamic and renal parameters in rats with Chronic Heart Failure (CHF) following left Coronary Artery Ligation (CAL). Approach: Forty eight male Sprague-Dawley rats (220-240 g) were divided into sham and CAL groups. Myocardial infarction was induced by left CAL. All rats were further subdivided into untreated and orally treated with ONO-9902 (300 mg kg-1 day-1) from the 1st to 6th weeks after the operation. At the 1st and 6th weeks after the operation, gene expression of plasma and renal NEP, plasma ANP, cGMP and aldosterone concentrations, urine volume, Na and ANP excretion, creatinine clearance and renal cGMP generation were measured. Results: CAL leads to sodium and water retention, increased renal NEP gene expression, plasma ANP and aldosterone and decreased renal cGMP generation and plasma NEP gene expression. Acute treatment of CAL rats by ONO-9902, at the 1st week after the operation, inhibited plasma and renal NEP gene expression with increased plasma ANP, which caused diuresis, natriuresis and increased renal cGMP generation. Moreover, chronic treatment of those rats by ONO-9902 decreased plasma and renal NEP gene expression, plasma aldosterone, increased plasma ANP but non significantly, and caused diuresis, natriuresis with increased renal cGMP generation. GFR was not significantly changed before or after treatment. Conclusion: Chronic treatment with NEP inhibitor decreases Na and water retention in rats with CHF by enhancing ANP action and suppressing aldosterone secretion. So, ONO-9902 may offer a new therapeutic approach in patients with CHF.

Natriuretic pro-peptides in idiopathic intracranial hypertension

Idiopathic intracranial hypertension is a disorder of unknown pathogenesis. Natriuretic peptides may be involved in intracranial pressure regulation, but cerebrospinal fluid (CNS) and plasma concentrations in this disorder are unknown. We evaluated venous and intrathecal concentrations of ANP, BNP and CNP precursor peptides in 40 patients with idiopathic intracranial hypertension and in 20 controls. Natriuretic pro-peptides were quantitated using processing-independent assays. In CSF, no differences in peptide concentrations between patients and controls were found (proANP: 239 ± 23 vs 231 ± 22 pmol/L, proBNP: < 2 pmol/L in all, proCNP: 1079 ± 318 vs 1138 ± 323 pmol/L). In plasma, proCNP was lower in IIH compared with controls (35.3 ± 4.8 pmol/L vs 43.8 ± 5.9 pmol/L, p < 0.0001). Moreover, plasma proBNP was significantly lower in patients compared with controls (47.1 ± 21.4 pmol/L vs 59.2 ± 22.0 pmol/L, p = 0.045). There were no associations between peptide concentrations and ICP and BMI, respectively. Plasma proANP and proCNP increased during 3 months follow-up ( p = 0.01 and p = 0.006), n = 12. We suggest that decreased plasma proCNP concentration in idiopathic intracranial hypertension may reflect endothelial dysregulation of vascular tone and may be a marker in this disease. Further studies of proCNP and endothelial function are needed to establish such role.

A CROSS-OVER COMPARISON OF ANTI-ALBUMINURIC EFFECTS AMONG 4 TYPES CALCIUM CHANNEL BLOCKERS ON CHRONIC KIDNEY DISEASE: PP.33.310

Background and Objectives: At the intervention for hypertension with chronic kidney disease (CKD), albuminuria is one of the pivotal targets as well as strict blood pressure (BP) control for organ protection. Calcium channel blocker (CCB) is one of the most expected agents for CKD. Currently CCBs have been classified by half-life, drug delivery system and channel types. We tested anti-albuminuric effect and humoral factors level of 4 types of CCBs in CKD. Methods: Subjects were 50 hypertensives with CKD (male/female 22/28, age 69.8±10.8yrs, SBP/DBP 164.7±17.1/92.3±12.2 mmHg, s-Cr 0.81±0.37 mg/dl, urinary albumin excretion (UAE) 69.4 (33.5–142.6) mg/gCr). CCBs were administered for 12 weeks in a crossover manner. Tested agents were nifedipine CR, a long biological half-life L type CCB with controlled release system, cilnidipine, an N/L type CCB, efonidipine, a T/L type CCB and amlodipine, a long biological half-life L type CCB with trans-membrane approach. Results: Comparable BP reductions were obtained. UAE at endpoints ware as follow (mg/gCr, *P < 0.05): nifedipine CR 30.8 (17.3–81.1),* cilnidipine 33.9 (18.0–67.7),* efonidipine 51.0 (21.2–129.8), amlodipine 40.6 (18.7–94.7). By all agents, significant augmentations were observed in PRA, angiotensin I and angiotensin II (AngII). AngII at cilnidipine was significantly lower than that at amlodipine. PAC at cilnidipine and efonidipine was significantly lower than that at amlodipine. Nifedipine CR significantly reduced ANP concentration. Conclusions: It is revealed for the first time that, although all tested drugs reduced UAE, only nifedipine CR and cilnidipine could reach statistical difference. Thus, it is suggested that, in respect of albuminuria reduction, the 2 CCBs might be favorable for organ protection in CKD.

Optimal water intake for the elderly: prevention of hypotremia

Aim The prevalence of hyponatremia in the elderly is quite high due to the rising of ADH and ANP concentrations which are part of eight physiologic changes. The complications are quite specific, among others, increased risk of bone fracture, declining of conciousness, and convulsion. The frequent cause of hyponatremia is high water intake. To achieve the optimal water intake designated as the highest water intake that did not cause hyponatremia and hypovolemia.

Long‐term postinfarction melatonin administration alters the expression of DHPR, RyR2, SERCA2, and MT2 and elevates the ANP level in the rat left ventricle

We investigated the effect of 2 wk continuous postinfarction subcutaneous melatonin supply on the expression of the rat left ventricular (LV) dihydropyridine receptor (DHPR), ryanodine receptor (RyR(2)), and sarco-endoplasmic reticulum Ca(2+)-ATPase2 (SERCA2), as they are fundamental proteins in cardiac contractility. The levels of plasma and LV atrial (ANP) and brain natriuretic peptide and melatonin were also measured, as was the expression of LV MT(1) and MT(2) receptors and pineal arylalkylamine N-acetyltransferase. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery and vehicle or melatonin (4.5 mg/kg per day) was administered by subcutaneous osmotic pumps. Echocardiography, real-time quantitative reverse transcription-polymerase chain reaction, and western blotting were used to analyze the samples. Echocardiography revealed that MI induced serious systolic LV dysfunction. The expression of DHPR, RyR(2), and SERCA2 mRNAs was significantly lower in the LVs of melatonin-treated MI rats compared with vehicle-treated rats (P < 0.01 for DHPR and P < 0.05 for RyR(2) and SERCA2). Melatonin also elevated the amount of LV MT(2) receptors to 1.9-fold (P < 0.05) and the concentration of LV ANP to over fivefold (P < 0.05) compared with vehicle rats after MI. Therefore, the results suggest that melatonin may influence the cardiac contractility after MI by regulating the expression of DHPR, RyR(2), and SERCA2, and melatonin receptors, particularly MT(2)s, might contribute to the postinfarction cardioprotective actions of melatonin. Furthermore, the finding of the relationship between melatonin and ANP suggests a novel mechanism for melatonin in protecting the heart after MI.

Atrial fibrillation ablation: beyond electro-mechanical matters

Since atrial fibrillation is the most frequent arrhythmia in the western world (with a predictable increase in the future, due to aging), treatment strategy has gained outstanding interest also for social and economic implications.1 Recently, Sacher et al. 2 focused on endocrine and mechanical implications of sinus rhythm (SR) restoration after radiofrequency ablation (RFA). The SR was associated with decrease in ANP and BNP coupled with an improvement in mechanical cardiac function in patients with and without impaired left ventricular ejection fraction (LVEF) after RFA. However, some observations are needed: (i) ANP and BNP concentrations drop the day after RFA despite volume …