Influence Of Atrial Natriuretic Peptide Research Articles

Atrial Natriuretic Peptide Promotes Neurite Outgrowth and Survival of Cochlear Spiral Ganglion Neurons in vitro Through NPR-A/cGMP/PKG Signaling.

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3’,5’-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptors (NPRs) by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats

Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old rats (n=12). To determine whether this is a restorable deficit, the influence of atrial natriuretic peptide (ANP), either by infusion or blockade of its breakdown, was studied. ANP infusion was previously shown to enhance Bezold-Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute) also occurs in old rats (increased by 60+/-18% (Bezold-Jarisch reflex) and 91+/-15% (ramp baroreflex; P<0.05). Direct vagal stimulation in anesthetized animals showed that the target for ANP was not the cardiac vagus itself in old rats (n=7), although in young rats only, we confirmed the published finding that ANP enhances vagal bradycardia (by 58+/-14%, n=7). Neutral endopeptidase 24.11 degrades ANP and several other peptides. The neutral endopeptidase inhibitor candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex bradycardia in old rats (n=6) to levels similar to those in young neutral endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex control of heart rate is thus a feature of normal aging, and this deficit may be ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.

Immunomodulatory and Cytoprotective Function of Atrial Natriuretic Peptide

The atrial natriuretic peptide (ANP) was described as a peptide hormone synthesized and secreted by heart atria. It plays an important role in the regulation of volume homeostasis; however, the functions of ANP are not restricted to cardiovascular effects. The biological profile of ANP is much broader than originally thought. This article focuses on the immunomodulatory and anti-inflammatory functions of ANP addressing; for example, the influence of ANP on macrophage functions. Another important aspect of ANP reviewed here is its cytoprotective potential. The beneficial effect of ANP in preventing cell damage caused by ischemia and reperfusion warrants special attention. The therapeutic potential of ANP in organ preservation could be important for transplantation medicine.

Atrial natriuretic peptide secretion and body fluid balance after bilateral atrial appendectomy by the maze procedure

Objectives: One of the earliest recognized postoperative complications of the maze procedure was the fluid retention in the immediate postoperative period. Routine postoperative administration of diuretics markedly reduces the frequency and severity of the fluid retention. However, the cause of the abnormal fluid balance is still uncertain. Methods: We evaluated 24 patients: 15 patients underwent the maze procedure (maze group) and 9 patients did not (nonmaze group). Blood samples were obtained before and in the time course after operation for atrial natriuretic peptide measurement. To evaluate the influence of atrial natriuretic peptide on the body fluid balance, we also measured the amount of body fluid balance and the total doses of furosemide and dopamine administered after operation. To examine the effect of the maze procedure on atrial natriuretic peptide secretion in chronic phase, we measured plasma atrial natriuretic peptide levels during dynamic exercise in 21 patients who had undergone cardiac operations 2 years before. Results: Plasma atrial natriuretic peptide levels in the nonmaze group significantly increased after operation. In contrast, plasma atrial natriuretic peptide levels in the maze group did not increase, and these levels were significantly lower than in the nonmaze group. Although significantly greater doses of furosemide and dopamine were administered to the maze group than to the nonmaze group, the body fluid balance in the maze group was comparable with that in the nonmaze group in the early postoperative period. The response of atrial natriuretic peptide secretion by exercise was significantly attenuated in the maze group ( n = 12) compared with the nonmaze group ( n = 9) even 2 years after surgery, although there were no significant differences in heart rate or blood pressure during exercise between two groups. Conclusions: These results suggest that the maze procedure attenuates atrial natriuretic peptide secretion in the early postoperative period and persists in chronic phase. This attenuated atrial natriuretic peptide secretion may reduce the ability of the kidneys to handle fluid load early after surgery. (J Thorac Cardiovasc Surg 1998;116:213-9)

Influence of atrial natriuretic peptide on thymocyte development in fetal thymic organ culture

The aim of the present study was to examine the effect of atrial natriuretic peptide (ANP) on T-cell development. The addition of ANP (10 −6–10 −10 M, 7 days) to organ cultures of 14 day old fetal mouse thymuses (FTOC) resulted in a decreased cell yield (up to 65% of the amount in control cultures). Flow cytometric analysis revealed a decrease (up to 35%) in the percentage of the CD4 +CD8 + thymocytes accompanied by an increase (100%) of the CD4 −CD8 − cell population in FTOC incubated with ANP. Exposure of FTOC to ANP furthermore decreases the percentage of CD5 expressing cells and increases the mean size of thymocytes estimated by monitoring their forward scatter intensity (flow cytometry). Thus, ANP seems to affect maturation and differentiation of thymocytes.

The influence of atrial natriuretic peptide on fibrinolitic properties of rats' blood

The influence of atrial natriuretic peptide on fibrinolitic properties of rats' blood

Nonuniform enhancement of baroreflex sensitivity by atrial natriuretic peptide in conscious rats and dogs.

The influence of atrial natriuretic peptide (ANP) on the blood pressure (BP)-heart rate (HR) baroreflex was studied in conscious chronically instrumented dogs and rats. In both species, sigmoid steady-state baroreflex curves were constructed from the baroreflex changes in HR to alternating slow injections of vasopressor and vasodepressor drugs. When this method was used in dogs, ANP caused a small but significant (P < 0.05) enhancement of the sensitivity (22 +/- 10%) and curvature (26 +/- 10%) of the baroreflex, which was without a change in HR range. In rats, ANP had no significant effect on any baroreflex parameter derived from steady-state curves. By contrast, in the same rats, fast reflex HR responses to rapid increases in BP (ramp) exposed a substantial (81 +/- 21%) ANP-induced enhancement of baroreflex sensitivity. Contribution from arterial vs. nonarterial afferents to the baroreflex is not uniform between these two techniques (steady state reflects largely arterial baroreceptor input, ramp evokes a greater proportion of cardiopulmonary afferent activation). The present study demonstrated that baroreceptor HR reflex responses to ANP depend on the baroreflex techniques employed and probably exposed a selectivity by ANP for nonarterial baroreflex pathways.

Influence of atrial natriuretic peptide on cyclic nucleotides and amylase release in rat parotid salivary gland in vitro

Atrial natriuretic peptide (ANP), sodium nitroprusside and hydroxylamine increased cGMP accumulation in rat parotid acinar cells both in the presence and absence of forskolin but in a different manner. On the other hand, ANP decreased forskolin-stimulated cAMP accumulation, although sodium nitroprusside and hydroxylamine had no effect on cAMP accumulation. Amylase release stimulated by forskolin, dibutyryl-cAMP or isoproterenol was depressed by ANP, whereas sodium nitroprusside and hydroxylamine did not evoke the inhibition of forskolin-stimulated amylase release. These results suggest that the inhibition of cAMP accumulation and of amylase release by ANP were not mediated via cGMP produced by guanylate cyclase-A.

Influence of ANP on sympathetic nerve activity and chronotropic regulation of the heart.

Hypotension caused by atrial natriuretic peptide (ANP) is often not accompanied by the anticipated increases in heart rate or sympathetic nerve activity. The sympathetic inhibitory action of ANP occurs in cardiac and noncardiac sympathetic nerves, and has been demonstrated in conscious or anesthetized animals as well as in humans. The sympathetic inhibition by ANP occurs after atropinization but is abolished after vagotomy. Thus, ANP alters sympathetic nerve activity by influencing cardiopulmonary baroreceptors, which in turn is mediated by vagal afferents. In addition to the effects of ANP on cardiopulmonary baroreceptors, ANP affects arterial baroreceptors. ANP dilates the ascending aorta where some of the arterial baroreceptors are located, causing resetting of these arterial baroreceptors. When ANP is microinjected into the cerebroventricle or nucleus tractus solitarii, it causes inhibition of sympathetic nerve activity. It has been shown that ANP inhibits sympathetic ganglionic transmission and augments cardiac parasympathetic effects on heart rate. Thus, ANP may play important roles in cardiovascular regulation by influencing sympathetic nerve activity and heart rate in addition to the direct vasodilating and renal effects.

Angiotensin II-induced proliferation of cultured murine mesangial cells: inhibitory role of atrial natriuretic peptide.

Angiotensin II (ANG II), as a single factor, induces proliferation in a cultured murine mesangial cell line (MMC). This study was undertaken to evaluate a possible influence of atrial natriuretic peptide (ANP) on this ANG II-induced proliferation. ANP (10(-7) M) for 2 min significantly increased intracellular cGMP levels in MMC. This increase in cGMP was totally abolished when cells were preincubated for 5 min with 10(-7) M ANG II. Stimulation of intracellular cGMP formation by sodium nitroprusside was also decreased in the presence of ANG II. The ANG II-mediated inhibition of ANP-stimulated intracellular cGMP levels was blocked by Dupont 753, suggesting signal transduction through ANG II receptors of the AT1 class. ANP (10(-7) M) for 24 h completely abolished the ANG II-induced proliferation in MMC. However, 10(-7) M ANP had no significant effect on mitogenesis induced by platelet-derived growth factor or epidermal growth factor. Furthermore, ANP reduced the ANG II-stimulated expression of the proliferating cell nuclear antigen, a cofactor of polymerase delta that is active in the S-phase of the cell cycle. The addition of 10(-3) M N-monobutyryl-guanosine 3':5'-cyclic monophosphate or 8-bromo-guanosine 3':5'-cyclic monophosphate also blocked the ANG II-induced proliferation. ANP (10(-7)) M for 24 h had no significant influence on the expression (number and dissociation constant) of ANG II receptors as determined by binding assays. These results suggest that, besides the previously shown vasoconstrictive and vasodilating effects, complex interactions between ANG II and ANP exist that can modulate mesangial cell growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Peptide and the Baroreflex Control of Circulation

An emerging role for atrial natriuretic peptide (ANP) as a modulator of baroreflex function is suggested by a number of experimental observations. In several animal species and in humans, ANP appears to reset the baroreflex control of heart rate in a way that favors bradycardia and opposes cardioacceleration. In addition, ANP interferes with the reflexes originating from cardiopulmonary receptors in the control of vascular tone. The modulation of baroreflexes by ANP seems to be related, at least in part, to the interaction of the atrial peptide with the effects of angiotensin II. This influence of ANP on the baroreflex control of circulation may be important in short-term cardiovascular adaptations, and may have particular relevance to conditions characterized by volume overload and impaired baroreflex function, such as certain forms of hypertension and congestive heart failure.

Influence of atrial natriuretic peptide on mammalian large intestine

Atrial natriuretic peptide is distributed in a number of organs including the large intestine. Atrial natriuretic peptide has potent diuretic and natriuretic properties and appears to play a central role in fluid and electrolyte homeostasis by an action on the kidney. We examined the influence of atrial natriuretic peptide on mammalian colon because this organ is also intimately involved in homeostasis. Segments of the distal colons of male Sprague-Dawley rats were stripped of muscle layers and mounted in flux chambers. Atrial natriuretic peptide, when added to the serosal side of the mucosa, in concentrations ranging from 10−8–10−5 M, caused a rapid, concentration-dependent increase in short-circuit current, transmucosal electrical potential difference, and conductance. The response to atrial natriuretic peptide was inhibited by (a) chloride-free solution on the serosal surface; (b) pretreatment of the tissues with the chloride channel blocker, diphenylamine-2-carboxylate (10−3 M mucosally); (c) pretreatment with d,l-verapamil (10−4 M mucosally and serosally); (d) calcium-free solution on the serosal surface; (e) pretreatment with tetrodotoxin (10−7 M to serosal surface); and (f) pretreatment with atropine (10−5 M serosally). However, the response to atrial natriuretic peptide was not influenced by pretreatment with amiloride (10−4 M to mucosal and serosal surfaces) or piroxicam (10−5 M serosally). Atrial natriuretic peptide did not elicit an increase in shortcircuit current and potential difference across T84 cells derived from a human colonic carcinoma cell line, suggesting that the response to atrial natriuretic peptide is not due to a direct effect on colonocytes. These findings suggest that atrial natriuretic peptide acts by a calcium-mediated secretory mechanism involving cholinergic nerves and is likely to be involved in the endogenous neurohumoral regulation of ion transport in the mammalian colon.