• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.469-478
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• 2022

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca²⁺ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.159-166
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• 2021

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 μM) and BQ788 (0.3 μM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 μM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 μM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxia-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 μM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 μM) and LY294002 (10.0 μM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.31-31
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• 2003

Cardiac atrium is now well-known as an endocrine organ which secretes atrial natriuretic peptide (AMP), participating in the regulation of body fluid and blood pressure. ANP is released mainly from cardiac muscle cells in response to various physiological and pathological conditions to induce atrial stretch. Ca$\^$2+/ may be one of the most important factors affecting ANP secretion even though controversy still persists. The aim of the present study is to investigate the effect of lysophosphatidylcholines (LPCs) and moxonidine on atrial hemodynamics and ANP secretion in hypertrophied atria. LPC is an endogenous phospholipid released from cell membrane during ischemia, and moxonidine is a imidazoline 1 (Il) receptor agonoist.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.69-69
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• 2006

• 한국동물학회지
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• 제35권3호
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• pp.263-270
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• 1992

Responses of immunoreactive atrial natriuretic peptide (ir-ANP) to environmental temperature were studied in the freshwater catfish, Silums usotus, acclimated at various temperatures for one week. According to increase in environmental temperature, plasma sodium and chloride concentrations, and osmolality were significantly increased, while hematocrit showed a marked decrease. When the catfishes frere acclimated at cold $(3^{\circ}C)$ or warm $(18^{\circ}C)$ temperatures, ir-ANP contents in the atrium and bulbus arteriosus were significantly lower than those at $9^{\circ}C.$ However, ventricular contents of ir-ANP urere not different among the three groups.Levels of plasma ir-ANP in the catfish increased in response to the increment of acclimated temperature. On the basis of these results, we suggest that the environmental temperature may modulate synthesis and secretion of ir-hUP in the fish. We also suggest that changes of plasma ir-ANP levels may be associated with the control of body fluid homeostasis.

• 동의생리병리학회지
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• 제30권1호
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• pp.40-46
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• 2016

Many medicinal plants have been used for the treatment of edema, jaundice, and gonorrhea in traditional Oriental medicine. This screening study was designed to search the positive inotropic effects of herbal extracts in beating rabbit atria. Aquarius extracts of twenty six herbs were examined in atrial mechanical dynamics such as pulse pressure and stroke volume and atrial natriuretic peptide (ANP), one of the main hormones involved in the regulation of the body fluid and blood pressure homeostasis in perfused beating rabbit atria. Sophora flavescens Ait., Rheum officinale Baill., Acorus gramineus Sol., Chelidonium majus L., Pulsatilla koreana Nakai., Reynoutria japonica Houtt., Euphorbia lathyris L., Pyrrosia lingua (Thunb.) Farwell, Poncirus trifoliata Rafin., Anemarrhena asphodeloides Bunge, Kochia scoparia Schrad. significantly increased stroke volume and pulse pressure. However, those herbal extracts were not induced ANP secretion. We clarified the eleven herbal extracts for the positive inotropic effect independent of ANP secretion in beating rabbit atria. Thus these results provide a beneficial data for the treatment of the impairment of body fluid and blood pressure in traditional Oriental medicine.

• 한국임상수의학회지
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• 제29권2호
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• pp.148-153
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• 2012

Atrial natriuretic peptide (ANP)은 여러 가지 다양한 심근질환과 연관성이 있는 것으로 알려져 있으나 심근경색에서 ANP의 변화에 대해서는 명확하게 밝혀져 있지 않다. 따라서 본 연구에서는 흰쥐 심근경색 모델을 활용하여 혈장내 ANP의 변화를 살펴보아 심근경색에서 ANP의 역할을 규명해보고자 하였다. 수컷 흰쥐 60일령에서 왼심장동맥을 결찰 하여 심근경색 모델을 만들었고 개흉하여 sham 대조군을 삼았다. 각각의 실험군과 대조군을 수술 후 1, 3, 6, 12, 18시간과 1, 3, 5, 7, 14 및 30일에 희생시켜 실험에 사용하였다. 심근경색의 크기는 planimetry와 perimetry법을 적용하여 측정하였고 혈장내 ANP 농도는 방사면역측정법을 적용하여 측정하였다. 왼심장동맥을 결찰한 실험군에서 평균 심근경색의 크기는 왼심실의 39.6-44.5%이었고 유의성 있는 차이는 없었다. 혈장내 ANP 농도는 심근경색 후 1, 3, 6, 12, 18 및 24시간에 대조군에 비하여 명확하게 증가하였으나 3, 5, 7, 14 및 30일령에서 ANP 농도는 대조군에 비하여 유의성 있는 차이를 나타내지 않았다. 이러한 결과는 수컷 흰쥐에서 혈장내 ANP 농도는 심근경색 초기에 명확하게 증가함을 입증하였고 급성심근경색의 진단을 위한 생체표지인자로 이용할 수 있는 가능성을 제시해주고 있다.

• 대한의생명과학회지
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• 제24권2호
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• pp.64-75
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• 2018

CCN3 (also known as NOV, Nephroblastoma overexpressed) proteins are involved in various pathologies during different developmental stages. We have previously shown that intracellular levels and normal extracellular secretion of CCN3 are important for neuronal differentiation. Furthermore, we demonstrated that a single amino acid in the CCN3 TSP-1 domain is important for extracellular secretion and that palmitoylation of CCN3 is required in this process. However, the effect of abnormal CCN3 accumulation on cells remains to be studied. Here, we found mutations in the TSP-1 domain of CCN3 that led to intracellular accumulation and abnormal aggregation of CCN3. It was observed that this mutation resulted in a phenomenon similar to neurodegeneration when overexpressed in the developing mouse cortex. This mutation also confirmed the activation of apoptotic gene expression in Neuro2a cells. In addition, we confirmed the in vivo transcriptional changes induced by this mutation using microarray analysis. We observed a significant increase in the expression of Anp32a, an apoptosis-related gene. Collectively, these results indicate that a single mutation in CCN3 can lead to abnormal cell death if it shows intracellular accumulation and abnormal aggregation.

• The Korean Journal of Physiology
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• 제24권2호
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• pp.261-268
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• 1990

It has long been suggested that the cardiac atrium is a low pressure volume receptor controlling body fluid volume and blood pressure. Recently, the cardiac atrium has been found to contain a family of powerful peptides. To clarify the relationship between high blood pressure and the biologically active atrial peptides, experiments were done to define the characteristics of atrial natriuretic peptide secretion in the isolated perfused atria of renal hypertensive rats. Higher concentrations of plasma atrial natriuretic peptide and renin activity were observed in the two-kidney, one clip hypertensive rat compared to the normotensive rat. Atrial volume changes in response to pressure elevations were attenuated in hypertensive rats compared to normotensive rats. Incremental response to atrial volume changes in ANP secretion was accentuated in hypertensive rats. These date suggest that the accentuated atrial natriuretic peptide response to volume changes of hypertensive rats may be a physiological or pathphysiological adaptation to the high blood pressure and may be, at least in part, responsible for the elevated levels of plasma atrial natriuretic peptide observed in hypertensive rats.

• The Korean Journal of Physiology and Pharmacology
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• 제10권3호
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• pp.149-154
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• 2006

Selective inhibition of phosphodiesterase (PDE) 5 opened a new therapeutic approach for cardiovascular disorders. Therefore, the effect of PDE5 inhibition on the cardiac function should thoroughly be defined. The purpose of the present study was to define the effects of sildenafil, a selective inhibitor of PDE5, on the atrial cGMP efflux, atrial dynamics, and the release of atrial natriuretic peptide (ANP). By perfusing rabbit left atria to allow atrial pacing, changes in atrial stroke volume and pulse pressure, transmural extracellular fluid translocation, cGMP efflux, and ANP secretion were measured. SIN-I, an NO donor and soluble (s) guanylyl cyclase (GC) activator, and C-type natriuretic peptide (CNP), an activator of particulate (p) GC activator, were used. Sildenafil increased basal levels of cGMP efflux slightly but not significantly. Sildenafil in a therapeutic dose increased atrial dynamics (for atrial stroke volume, $2.84{\pm}1.71%$, n=12, vs $-0.71{\pm}0.86%$, n=21; p<0.05) and decreased ANP release ($-9.02{\pm}3.36%$, n=14, vs $1.35{\pm}3.25%$, n=23; p < 0.05), however, it had no effect on the SIN-1- or CNP-induced increase of cGMP levels. Furthermore, sildenafil in a therapeutic dose accentuated SIN-1-induced, but not CNP-induced, decrease of atrial pulse pressure and ANP release. These data indicate that PDE5 inhibition with sildenafil has a minor effect on cGMP levels, but has a distinct effect on pGC-cGMP- and sGC-cGMP-induced contractile and secretory function.