• Korean Journal of Veterinary Research
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• v.36 no.1
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• pp.65-74
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• 1996

Atrial Natriuretic Peptide(ANP) is a hormone with potent natriuretic, diuretic and relaxing properties of vascular smooth muscle. Specific chemical modulator responsible for the ANP secretion has not yet been found. Although atrial stretch of stretch-release is to be a major stimulus for the secretion of ANP, the precise mechano-molecular transduction mechanism responsible for its evoked secretion remains to be elucidated. It is interested to clarify the effect of superoxide anion in the stretch-induced ANP secretion. In order to investigate the effectg of $H_2O_2$ in the regulation of ANP secretion, a perfused model of left atrium of rats was used. The results obtained were as follows; 1. The ANP secretion and the extracellular fluid(ECF) translocation were accentuated by the effect of repetitive atrial distension-reduction volume at atrial pressure($4cmH_2O$). 2. The dilution curve showed to be in parallel between pure atriopeptin III (AP III) and perfusated buffer. 3. $H_2O_2(5{\times}10^{-4}M)$ accenturated a strectch-release induced increase of the ANP secretion. The amount of released ANP was significantly(p<0.01) increased. These results suggest that the superoxide anion may be involved in the regulatory mechanism of mechanically activated ANP release.

• Korean Journal of Veterinary Research
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• v.39 no.5
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• pp.930-937
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• 1999

Atrial natriuretic peptide(ANP) is a hormone with potent natriuretic, diuretic and relaxing properties on vascular smooth muscle. Specific chemical modulator in response for the ANP secretion has not been found yet. Therefore, we have investigated the role of $Ca^{2+}$ responsible for the regulation of ANP induced by protein kinase C(PKC) on mechanically stretch-induced ANP secretion in the rat atria. The results obtained were as follows ; 1. ANP secretion and ANP concentration were increased to more in $Ca^{2+}$-free buffer than in the Kreb-Henseleit buffer on mechanically stretch-induced ANP secretion(p < 0.05), but extracellular fluid translocation(ECF) was not significant. Phorbol 12-myristate 13-acetate(PMA, $10^{-7}M$) induced ANP secretion and ANP concentration in $Ca^{2+}$-free buffer shown to more accentuate on mechanically stretch-induced ANP secretion than in the $Ca^{2+}$-free buffer(p < 0.05), but ECF translocation was not significant. 2. In the presence of ryanodine($3{\times}10^{-6}M$), PMA($10^{-7}M$) induced ANP secretion and ANP concentration in the Kreb-Henseleit buffer were shown to more increase on mechanically stretch-induced ANP secretion than in the ryanodine($3{\times}10^{-6}M$) with the Kreb-Henseleit buffer(p < 0.05), but ECF translocation was not significant. 3. In the presence of ryanodine($3{\times}10^{-6}M$), PMA($10^{-7}M$) induced ANP secretion and ANP concentration in the $Ca^{2+}$-free buffer was shown to more increase on mechanically stretch-induced ANP secretion than in the ryanodine($3{\times}10^{-6}M$) with the $Ca^{2+}$-free buffer on mechanically induced ANP secretion(p < 0.05), but ECF translocation was not significant. The results suggest that PKC-induced ANP secretion may not be related to the change of $Ca^{2+}$ on mechanically induced ANP secretion in the rat atria.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.65-70
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• 1997

In order to investigate the effect of ANP on surfactant secretion from alveolar type II cell(AT II cell) during circulatory derangement in adult respiratory distress syndrome (ARDS), the secretion of surfactant from AT II cells was evaluated in purely isolated AT II cultures from rat lungs. For the simulation of sympathetic stimulation during circulatory derangement, primary AT II cultures were incubatedwith isoproterenol and IBMX. In this isoproterenol stimulated AT II cells, ANP were added in the media for the investigation of effect of ANP on surfactant secretion from AT II cells. For the evaluation of surfactant secretion, $[^3H]-methylcholine$ was incorporated and the level of radiolabelled choline chloride secreted from the cells was determined. As previously reported, isoproterenol and IBMX stimulated surfactant secretion from AT II cells. Isoproterenol showed synergistic increase of surfactant secretion with IBMX in AT II cells. In isoproterenol stimulated AT II cells, physiological level of ANP inhibited the secretion of surfactant in primary cultures of AT II cells. On the basis of these experimental it is suggested that, in association with ciculatory change during ARDS, increased secretion of ANP by the pulmonary edema, hypoxia and congestive heart heart failure might aggravate the symptoms of ARDS by reduction of surfactant secretion from AT II cells.

• Journal of Chest Surgery
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• v.33 no.5
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• pp.398-406
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• 2000

Background: Cardiac atrium is an endocrine gland secreting a family of natriuretic peptides. The secretion of atrial natriuretic peptide(ANP) had been shown to be controlled by variable factors. The change in atrial dynamics have been considered as one of the most prominent stimuli for the stimulation of ANP secretion. Hypoxic stress has been shown to increase cardiac ANP secretion. However, the mechanism by which hypoxia increases ANP secretion cardiac ANP secretions. However, the mechanism by which hypoxia increases ANP secretion has not to be defined. Therefore, the purpose of the present study was tow-fold: to develop a protocol to defined the effect of hypoxia on ANP secretion in perfused beating rabbit atria and to clarify the mechanism responsible for the accentuation by hypoxia of ANP secretion. Material and Method: Experiments have been done in perfused beating rabbit atria. ANP was measured by radioimmunoassay. Result: Hypoxic stimulus with nitrogen decreased atrial stroke volume. The decrease in atrial stroke volume recovered basal level during the period of recovery with oxygen. ANP secretion and the concentration of perfusate ANP in terms of extracellular fluid(ECF) translocation which reflects the rate of myocytic release of ANP were increased by hypoxia and returned to basal levels during the recovery. Changes in ECF translocation paralleled by hypoxia and returned to basal levels during the recovery. Changes in ECF translocation paralleled to that of atrial stroke volume. At the start of recovery in atrial storke volume, ECF tranalocation incrased for several minutes. The above responses were stable and reproducible. Glibenclamide treatment prevented the recovery in atrial stroke volume. Increments by hypoxia of ANP secretion and ANP concentration were suppressed by glibenclamide. Conclusion: These results indicate that hypoxia incrased atrial myocytic ANP release and that the mechanism responsible for the accentuation is partially related to the change in K+ATP channel activity.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.667-674
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• 2017

Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and from C-terminal by Ang converting enzyme (ACE) to generate several truncated angiotensin peptides (Angs). The truncated Angs have different biological effects but it remains unknown whether Ang-(4-8) is an active peptide. The present study was to investigate the effects of Ang-(4-8) on hemodynamics and atrial natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial stretch caused increases in atrial contractility by 60% and in ANP secretion by 70%. Ang-(4-8) (0.01, 0.1, and $1{\mu}M$) suppressed high stretch-induced ANP secretion in a dose-dependent manner. Ang-(4-8) ($0.1{\mu}M$)-induced suppression of ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1 receptor ($AT_1R$) but not by an antagonist of $AT_2R$ or $AT_4R$. Ang-(4-8)-induced suppression of ANP secretion was attenuated by the pretreatment with inhibitor of phospholipase (PLC), inositol triphosphate ($IP_3$) receptor, or nonspecific protein kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to Ang II. However, Ang-(4-8) $10{\mu}M$ caused an increased mean arterial pressure which was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8) suppresses high stretch-induced ANP secretion through the $AT_1R$ and $PLC/IP_3/PKC$ pathway. Ang-(4-8) is a biologically active peptide which functions as an inhibition mechanism of ANP secretion and an increment of blood pressure.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.125-133
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• 2022

Carbon monoxide (CO) is a known gaseous bioactive substance found across a wide array of body systems. The administration of low concentrations of CO has been found to exert an anti-inflammatory, anti-apoptotic, anti-hypertensive, and vaso-dilatory effect. To date, however, it has remained unknown whether CO influences atrial natriuretic peptide (ANP) secretion. This study explores the effect of CO on ANP secretion and its associated signaling pathway using isolated beating rat atria. Atrial perfusate was collected for 10 min for use as a control, after which high atrial stretch was induced by increasing the height of the outflow catheter. Carbon monoxide releasing molecule-2 (CORM-2; 10, 50, 100 μM) and hemin (HO-1 inducer; 0.1, 1, 50 μM), but not CORM-3 (10, 50, 100 μM), decreased high stretch-induced ANP secretion. However, zinc porphyrin (HO-1 inhibitor) did not affect ANP secretion. The order of potency for the suppression of ANP secretion was found to be hemin > CORM-2 >> CORM-3. The suppression of ANP secretion by CORM-2 was attenuated by pretreatment with 5-hydroxydecanoic acid, paxilline, and 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, but not by diltiazem, wortmannin, LY-294002, or NG-nitro-L-arginine methyl ester. Hypoxic conditions attenuated the suppressive effect of CORM-2 on ANP secretion. In sum, these results suggest that CORM-2 suppresses ANP secretion via mitochondrial K_ATP channels and large conductance Ca²⁺-activated K⁺ channels.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.393-401
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• 2000

To define the postnatal changes in ANP secretion in response to mechanical stretch and atrial compliance, experiments have been done in perfused nonbeating rabbit atria with different ages: 1-day, 1-, 2-, 3-, 4-, and 8-wk-old. In 1-day-old-rabbits, an increase in intraatrial pressure resulted in an increase in atrial volume, which was higher than that in 1-wk-old rabbits. Increases in atrial volume stimulated the secretion of ANP with concomitant translocation of extracellular fluid (ECF) into the atrial lumen. However, mechanically stimulated ECF translocation was lower in 1-day-old rabbits than that in 1-wk-old rabbits. Therefore, positive relationship between mechanically stimulated ECF translocation and ANP secretion was shifted upward in 1-day-old rabbits, as compared to 1-wk-old rabbits. Changes in atrial volume and ECF translocation were gradually increased with aging and reached the peak value at 4 wk. The stretch-induced ANP secretion in terms of ECF translocation (the interstitial ANP concentration) was also increased with aging and reached the peak value at 4 wk. The interstitial ANP concentration was dependent on the atrial content of ANP. These data suggest that the higher level of atrial ANP secretion is related to the postnatal changes in atrial volume and unidentified factor.

• The Korean Journal of Zoology
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• v.34 no.1
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• pp.8-19
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• 1991

Atrial natriuretic peptide(ANP)의 유리기전에 대한 특성을 알아보고자, 흰쥐의 적출심장 관류모형을 사용하여 연구한 바 다음과 같은 결과를 얻었다. 1. 심방을 확장시켰을 때 ANP의 유리는 촉진되었다. 그러나 과용량을 부하하면 확장기간보다 회복기간에 ANP의 유리가 현저하게 증가하였다. 2. Epinephrine과 phenylephrine을 주입하면 ANP의 유리 량이 증가했으나, isoproterenol을 주입하면 심박수와 우심방 내압이 현저하게 증가했는데도 ANP의 유리량은 오히려 감소하였다 3. 미주신경을 자극하면 심박수의 현저한 감소에도 불구하고 ANP의 유리량은 증가하였다. 이상과 같은 결과에서 볼 때 결론적으로, 심방의 용량부하에 의해 심방근의 신장수용체가 자극을 받아 ANP의 유리가 촉진되는 것은 분명하고, 심방근이 확장할 때 보다는 확장 후 다시 원래의 길이로 환원될 때 ANP가 유리될 것으로 사료된다. 그리고 ANP의 유리에 대한 adrenergic조절은 o-receptor가 관련되어 있으며 심박수와 심방내압이 ANP의 유리를 변화시키는 데는 반드시 필수적인 인자가 아닌 것으로 여겨진다. 또한 특히 미주신경의 자극으로도 ANP의 유리가 조절될 수 있다는 것이 본 연구를 통해 새로이 발견되었다.

• The Korean Journal of Physiology
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• v.27 no.1
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• pp.57-66
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• 1993

Effects of a voltage dependent calcium channel antagonist, nifedipine, on the responses of blood pressure, and secretion of atrial natriuretic peptide (ANP) and aldosterone to angiotensin II (Ang II) were compared in male Wistar and spontaneously hypertensive rats (SHR). A low, control or high sodium diet (2, 10 or 25 mmol Na/100 g diet) was fed for 6 weeks from the age of 6 weeks. On the morning of the experiment catheters were inserted under ether anesthesia in the femoral artery for pressure recording and blood sampling, and in the femoral vein for drug infusion. Ang II was infused at a rate of 250 ng/kg/min for 20 min. Nifedipine mixed with Ang II was infused at a rate of $16{\mu}g/kg/min$ for 20 min. Arterial blood samples were collected before and after infusion of Ang II with or without nifedipine. The control plasma level of aldosterone was inversely related to the amount of salt intake, whereas the plasma ANP level was not different between the salt groups. SHR showed a higher basal plasma ANP but a lower aldosterone concentration than Wistar rats. Infusion of Ang II produced a significant increase in blood pressure and plasma levels of aldosterone and ANP: The % increase was not significantly different either between the salt groups or between SHR and Wistar rats. SHR showed a greater pressor response to Ang II but a remarkably smaller decrease in heart rate after Ang II infusion than Wistar rats, With increasing sodium intake, the effect of Ang II on aldosterone secretion was decreased, whereas that on ANP secretion or blood pressure was not changed. Nifedipine decreased the responses of blood pressure and heart rate to Ang II in all groups. Nifedipine caused almost a complete inhibition of Ang II induced ANP secretion, but only a partial inhibition of Ang II induced aldosterone secretion or vasoconstriction. These results indicate that calcium dependent processes were involved in Ang II induced vasoconstriction, and secretions of aldosterone and ANP. However, the calcium dependent process far ANP secretion was considerably different from that for aldosterone secretion or vasoconstriction evoked by ang II. The ang II induced increase in ANP secretion appeared to be caused primarily by activating voltage-dependent calcium channels, whereas Ang II induced aldosterone secretion and vasoconstriction was not.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.293-300
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• 2017

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.