Decrease In Atrial Natriuretic Peptide Research Articles

(R,S)-Ketamine Promotes Striatal Neurogenesis and Sensorimotor Recovery Through Improving Poststroke Depression–Mediated Decrease in Atrial Natriuretic Peptide

BackgroundPoststroke social isolation could worsen poststroke depression and dampen neurogenesis. (R,S)-ketamine has antidepressant and neuroprotective effects; however, its roles and mechanisms in social isolation–mediated depressive-like behaviors and sensorimotor recovery remain unclear. MethodsMice were subjected to transient middle cerebral artery occlusion, and then were pair-housed with ovariectomized female mice or were housed isolated (ISO) starting at 3 days postischemia. ISO mice received 2 weeks of (R,S)-ketamine treatment starting at 14 days postischemia. Primary ependymal epithelial cells and choroid plexus epithelial cells were cultured and treated with recombinant human atrial natriuretic peptide (ANP) protein. ResultsThe poststroke social isolation model was successfully established using middle cerebral artery occlusion combined with poststroke isolation, as demonstrated by a more prominent depression-like phenotype in ISO mice compared with pair-housed mice. (R,S)-ketamine reversed ISO-mediated depressive-like behaviors and increased ANP levels in the atrium. The depression-like phenotype was negatively correlated with ANP levels in both the atrium and plasma. Atrial GLP-1 and GLP-1 receptor signaling was essential to the promoting effects of (R,S)-ketamine on the synthesis and secretion of ANP from the atrium in ISO mice. (R,S)-ketamine also increased ANP and TGF-β1 levels in the choroid plexus of ISO mice. Recombinant human ANP increased TGF-β1 levels in both the primarily cultured ependymal epithelial cells and choroid plexus epithelial cells. Furthermore, (R,S)-ketamine increased TGF-β1 levels in the ischemic hemisphere and promoted striatal neurogenesis and sensorimotor recovery via ANP in ISO mice. Conclusions(R,S)-ketamine alleviated poststroke ISO-mediated depressive-like behaviors and thus promoted striatal neurogenesis and sensorimotor recovery via ANP.

Effect of aliskiren in chronic kidney disease patients with refractory hypertension undergoing hemodialysis: a randomized controlled multicenter study

Applying a direct renin inhibitor (DRI) to advanced stage chronic kidney disease (CKD) patients is a matter of controversy. The purpose of this study was to evaluate the effect of the DRI, aliskiren, in patients with therapy-resistant hypertension undergoing hemodialysis (HD). The study was a prospective, randomized multicenter trial exploring the antihypertensive effect of aliskiren in comparison with amlodipine, a calcium channel blocker, in patients undergoing HD. A total of 83 participants whose blood pressure (BP) had previously been treated with more than one antihypertensive agent and not having achieved the BP goal of <140/90 mmHg were randomly assigned to either aliskiren 150 mg or amlodipine 5 mg as an add-on therapy. A significant decrease in pre-dialysis clinic BP and home BP was found only in the amlodipine group and not in the aliskiren group. In contrast, there was a significant decrease in atrial natriuretic peptide (ANP) in the aliskiren group but not in the amlodipine group. N-terminal pro-B-type natriuretic hormone remained unchanged in both groups. Aliskiren significantly reduced angiotensin I and II, plasma renin activity, and increased plasma renin content. However, such changes were not observed in the amlodipine group. Amlodipine, not aliskiren, effectively reduces BP in CKD patients with refractory hypertension undergoing HD. Aliskiren suppresses the renin-angiotensin system and reduces ANP. Whether the DRI is beneficial in improving cardiovascular events in patients undergoing HD remains to be elucidated in future studies.

Abstract 1889: Cardiac Resynchronization Therapy With Biventricular Pacing Improves Renal Function in Heart Failure Patients With Reduced Glomerular Filtration Rate

Background: Renal dysfunction has emerged as an important independent prognostic factor in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony. We hypothesized that CRT would also improve glomerular filtration rate as estimated by the abbreviated MDRD equation (eGFR) in patients with reduced eGFR. Methods: This is a retrospective analysis of the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, which evaluated CRT in HF patients with NYHA class III–IV, ejection fraction ≤35%, QRS ≥130 ms, and stable medical regimen. Patients were evaluated before implantation and 6 months after randomization to control (CRT device OFF, n=225) or CRT (n=228). Patients were categorized according to their baseline eGFR: ≥90 (category A), 60≤eGFR&lt;90 (category B), and 30≤eGFR&lt;60 (category C) mL/min per 1.73m 2 . Changes in eGFR were also correlated with changes in other parameters in univariate analysis. Results: At baseline, reduced eGFR was associated with ischemic etiology, increased age, mitral regurgitation, and neurohumoral activation. CRT increased LV ejection fraction and decreased LV volumes and mitral regurgitation in all categories. Importantly, CRT improved eGFR (p=0.003) and reduced blood urea nitrogen (p=0.008) compared to control in category C, but not A (p=0.75/p=0.41) and B (p=0.43/p=0.89). In addition, only in category C did atrial natriuretic peptide decrease, suggesting reduced atrial distention and filling pressures with CRT in this group with impaired eGFR. In univariate analysis, changes in eGFR correlated weakly but significantly with changes in aldosterone (r=−0.22), plasma renin activity (r=−0.19, norepinephrine (r=−0.16), and mean blood pressure (r=+0.14), a pattern consistent with reduced neurohumoral activation due to increased systemic and renal perfusion pressure. Conclusions: CRT increased eGFR and reduced blood urea nitrogen in HF patients with reduced baseline eGFR. By improving cardiac function, CRT can indirectly improve renal function, underscoring the importance of cardiorenal interaction and providing another mechanism for the beneficial effects of CRT.

Lack of endothelial nitric oxide synthase decreases cardiomyocyte proliferation and delays cardiac maturation

We recently demonstrated that deficiency in endothelial nitric oxide synthase (eNOS) results in congenital septal defects and postnatal heart failure. The aim of this study was to investigate the role of eNOS in cardiomyocyte proliferation and maturation during postnatal development. Cultured eNOS knockout (eNOS(-/-)) cardiomyocytes displayed fewer cells and lower bromodeoxyuridine (BrdU) incorporation in vitro compared with wild-type (WT) cardiomyocytes (P < 0.05). Treatment with the nitric oxide (NO) donor diethylenetriamine NONOate increased BrdU incorporation and cell counts in eNOS(-/-) cardiomyocytes (P < 0.05). Inhibition of nitric oxide synthase activity using N(G)-nitro-L-arginine methyl ester decreased the level of BrdU incorporation and cell counts in WT cardiomyocytes (P < 0.05). Vascular endothelial growth factor (VEGF) increased the level of BrdU incorporation in cultured WT cardiomyocytes in a dose- and time-dependent manner (P < 0.05). Conversely, VEGF did not alter BrdU incorporation in eNOS(-/-) cardiomyocytes (P = not significant). Furthermore, deficiency in eNOS significantly decreased BrdU labeling indexes in neonatal hearts in vivo. Although WT hearts displayed a rapid decrease in atrial natriuretic peptide (ANP) expression in the first week of neonatal life, ANP expression in eNOS(-/-) hearts remain elevated. Our study demonstrated that NO production from eNOS is necessary for postnatal cardiomyocyte proliferation and maturation, suggesting that eNOS plays an important role during postnatal heart development.

Effects of mechanical ventilation on the kidney

Mechanical ventilation with positive airway pressure has an inhibitory effect on the kidney, which results in a decrease of renal water and sodium excretion. Physical, hormonal, and nervous factors are involved in this process. The increase of intrathoracic pressure results in a decrease of atrial transmural pressures, cardiac output, and mean arterial pressure. Low-pressure and high-pressure baroreceptors are unloaded, and plasma vasopressin concentrations and sympathetic activity increase. The decrease of renal perfusion and the increase of renal nerve sympathetic activity stimulate the renin-angiotensin system. Angiotensin II formation stimulates aldosterone production. Whether a decrease of atrial natriuretic peptide plays a major role is not yet clear. The resulting (physiologic) reaction of the kidney is an increased reabsorption of water and sodium. The effects are directly related to the increase of intrathoracic pressure (which also depends on the level of positive end-expiratory pressure). They can be partially attenuated by extracellular volume loading.

Hormonal response to restraint in rhesus monkeys

The purpose of this study was to characterize the hormonal responses to a restraining system in four adult male rhesus monkeys (Macaca mulatta) in preparation for a spaceflight project. After the monkeys were accustomed to food and water (Phase I), blood-volume-regulating hormones were measured during three phases: 10 days in a metabolic cage (Phase II), 16 days sitting in a restrained position in a specially designed metabolism chair (Phase III) and 10 days in metabolic cage (Phase IV). An increase of active renin (30%) and vasopressin (25%) was observed at the end of Phase III. A decrease of atrial natriuretic peptide (ANP), urodilatin, and sodium excretion occurred during the first days of Phase III. Catecholamines were unchanged. A dramatic increase (tenfold) in urinary excretion of growth hormone occurred during all of Phase III and at the beginning of Phase IV. These findings are similar to those found in man during isolation inactivity and during confinement stress.

Characteristics of ANP-binding sites in the adrenal capsules of term-pregnant rats

Significant increases of circulatory volume and plasma aldosterone levels are observed in pregnancy. We investigated whether a decrease of atrial natriuretic peptide (ANP) receptors in the adrenal zona glomerulosa (ZG) could explain the marked elevation of plasma aldosterone occuring during pregnancy. 125I-ANP binding was measured in competition experiments using rANP(1–28), ANP(4–23), a truncated analog which has high specificity for the ANP-C receptor, or a combination of both. Western blot experiments were also performed with an investigation into the effect of ANP on aldosterone secretion in adrenal capsule suspensions. 125I-ANP binding on adrenal ZG membranes was displaced by ANP(1–28) with an affinity ( K d) of 313 ± 39 and 323 ± 60 pM (NS) for pregnant and non-pregnant rats, respectively. The density of sites ( B max) decreased slightly but not significantly during pregnancy. Displacement experiments with ANP(4–23) demonstrated a B max of 137 and 134 fmol/mg of proteins (NS) for pregnant and non pregnant rats, respectively. Studies were performed to block the ANP-C site. Displacing the remaining 125I-ANP binding with ANP(1–28) led to an affinity constant and receptor density which were not significantly different between the two groups of rats. The results obtained with Western blots showed a single band of 123 kDa with no significant variations in ANP-R 1 receptors in the ZG during gestation. The sensitivity of potassium-, ACTH- or angiotensin II-stimulated aldosterone secretion to ANP was not altered by gestation. These data show that the apparent hyperaldosteronism found in normal term-pregnant rats is not the consequence of modifications in the affinity, number and properties of ANP receptor types or in the sensitivity of the aldosterone response to ANP.

Effects of sham hemodialysis on plasma levels of vasoactive peptides in patients with uremia.

Changes in plasma levels of vasoactive peptides during hemodialysis have mainly been attributed to changes in plasma volume and osmolality. This study investigated the effect of the extracorporeal circulation on plasma levels of vasoactive peptides, noradrenaline, and renin. Eleven stable hemodialysis patients were studied during sham dialysis for 60 min using a Cuprophan dialyzer (Alwall GFE11, Gambro AB, Lund, Sweden). With regard to vasoconstrictors, there was an increase in noradrenaline (NA) (13%, p < 0.05) and renin (PRA) (32%, p < 0.05), while arginine vasopressin and neuropeptide Y remained unaltered. Concerning vasodilators, an increase in substance P (SP) (23%, p < 0.05) and vasoactive intestinal peptide (VIP) (15%, p < 0.01) was observed, while a decrease in atrial natriuretic peptide (ANP) (17%, p < 0.05) and motilin (MOT) (24%, p < 0.01) occurred. Calcitonin gene related peptide and beta endorphin were unaltered. A decrease in blood pressure was observed, while heart rate remained unchanged. The authors conclude that the extracorporeal circulation, per se, affects plasma levels of vasoactive substances and influences vascular stability. The decrease in ANP and MOT might be due to adsorption to the dialysis membrane. The increase in some vasoconstrictors (NA, PRA) and vasodilators (SP, VIP) might be induced by the blood-artificial surface contact, or by other factors, e.g., heparin or cooling of the blood during the procedure.

Effect of frusemide on atrial natriuretic peptide, guanosine cyclic monophosphate, angiotensin II, aldosterone, vasopressin, prostaglandin E2 and blood volume in the nephrotic syndrome.

Blood volume, plasma concentrations of atrial natriuretic peptide, guanosine cyclic monophosphate (cGMP), angiotensin II, aldosterone and arginine vasopressin, and urinary excretion rate of prostaglandin E2, cGMP, sodium, and water were determined before and after intravenous administration of frusemide 0.75 mg/kg body-weight in nine patients with the nephrotic syndrome and 15 control subjects. The decrease in blood volume and the increase in urinary sodium and water excretion after fusemide were significantly reduced in the nephrotic patients compared with the controls. Atrial natriuretic peptide was reduced after frusemide both in patients (6.2 to 4.9 pmol/l, medians, P less than 0.05) and controls (5.9 to 4.8 pmol/l, P less than 0.01), but the nadir was delayed in the patients, and cGMP in plasma and urine was reduced only in the controls. The angiotensin II increase was delayed in the patients and aldosterone increased only in the controls. Basal urinary excretion of prostaglandin E2 was less in the nephrotic patients than in the controls (P less than 0.05), but after frusemide the prostaglandin E2 excretion rate increased in the patients (0.25 to 0.62 pmol/min, P less than 0.05), but not in the controls (0.46 to 0.39 pmol/min). In conclusion, reduced water and sodium excretion after frusemide in the nephrotic syndrome is accompanied by a diminished reduction of blood volume, a delayed decrease in atrial natriuretic peptide, and a blunted increase in angiotensin II and aldosterone compared with healthy subjects. Sodium excretion after frusemide may be more dependent on PGE2 production in nephrotic patients than in healthy subjects.

Atrial natriuretic peptide decrease during spontaneous breathing with continuous positive airway pressure in volume-expanded healthy volunteers: Frass M, Popovic R, Hartter E, et al: Crit Care Med 16:831–835, 1988

Atrial natriuretic peptide decrease during spontaneous breathing with continuous positive airway pressure in volume-expanded healthy volunteers: Frass M, Popovic R, Hartter E, et al: Crit Care Med 16:831–835, 1988