• Journal of Life Science
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• v.22 no.3
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• pp.398-406
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• 2012

This study aimed to examine whether the polygenic profile of ACE ID and ACTN3 R577X polymorphisms is associated with muscle power performance in Korean athletes. For this study, 106 top-class power athletes (top-class group), 158 elite power athletes (elite-class group), and 676 healthy adults (control) aged 18-39 yrs were recruited and their genotypes were analyzed. The top-class group showed higher frequencies of the II genotype and I allele in ACE, as well as higher frequencies of the RR genotype and R allele in ACTN3 (top-class vs. control: 41.4% vs. 32.1% for II genotype, 67.1% vs. 57.7% for I allele, p<0.05; 42.3% vs. 29.0% for RR genotype, 65.3% vs. 54.8% for I allele, p<0.05). In the polygenic profile, the top-class group had significantly higher frequencies of combined-II/ID+RR/RX genotype than the control group (top-class vs. control: 82.9% vs. 66.7% for II/ID+RR/RX, p<0.05), and there was even a sharp increase in total genotype score (TGS) in this group compared to the elite-class and control groups ($66{\pm}0.9$ vs. $58{\pm}1.9$ vs. $56{\pm}2.3$, p<0.05). The combined-II/ID+RR/RX genotype showed the possibility of succussion in the top-class muscle power performance with an odds ratio of 2.3 (CI:1.4-4.1, p<0.05). These results suggested that ACE and ACTN3 need to interact with each other to affect muscle-power performance in an additive form. Furthermore, the polygenic profile of ACE and ACTN3 can predict muscle performance with high success in a homogeneous dominant combined genotype (II/ID+RR/RX). A further study could identify and combine other genes into ACE and ACTN3 for muscle strength.

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.92-100
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• 2013

Purpose: To investigate the clinicopathologic effects of cyclosporine A (CsA) in children with diseases characterized by mesangial immunoglobulin A deposits such as immunoglobulin A nephropathy (IgAN) and Henoch-Sch$\ddot{o}$nlein purpura nephritis (HSPN). Methods: We retrospectively reviewed the clinicopathologic outcomes of 54 children (IgAN, 36; HSPN, 18) treated with CsA. The starting dose of CsA was 5 mg/kg per day, and it was administered in 2 divided doses. The degree of proteinuria and pathologic changes in renal biopsies were evaluated before and after CsA treatment. Results: The mean protein to creatinine ratio decreased from $3.7{\pm}1.5$ to $0.6{\pm}0.4$(P <0.001), and 32 (59.2%) children achieved complete remission of proteinuria after 1-year CsA treatment. Among the 54 children, 24 maintained normal renal function and 25 exhibited microscopic hematuria or proteinuria at the end of CsA treatment. In the HSPN group, 3 children whose initial biopsies indicated class IIIb disease showed class II disease on follow-up, and the follow-up biopsies of 2 children who had class II disease indicated the same class II disease. In the IgAN group, cortical tubular atrophy occurred in 1 child, and no child with IgAN had cortical interstitial fibrosis or tubular atrophy after 1-year CsA treatment. No significant complications were found in the children treated with CsA. Conclusion: Our findings indicate that CsA treatment is effective and beneficial in reducing massive proteinuria and preventing progression to end-stage renal failure in children with glomerular diseases characterized by IgA deposits, such as IgAN and HSPN, within 1 year of treatment.

• Natural Product Sciences
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• v.19 no.1
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• pp.36-48
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• 2013

The aim of the present study was to investigate the effects of several fractions obtained from methylene chloride ($CH_2Cl_2$) extract of self-fermented pine needle (SFPNE) on the acetylcholine (ACh)-evoked CA release from the isolated perfused model of the rat adrenal medulla and to establish the mechanism of the most active fraction (Fr.)-induced inhibitory action on the CA release. We obtained 6 fractions from $CH_2Cl_2$ extract of self-fermented pine needle. For the ACh (5.32 mM)-evoked CA release, the following rank order of inhibitory potency was obtained: Fr.4-5 > Fr.8-11 ${\gg}$ Fr.3 > Fr.6 = Fr.7 > Fr.1-2. Fr. 4 - 5 (60 ${\mu}g/mL$) perfused into an adrenal vein for 90 min produced relatively time-dependent inhibition of the CA secretory responses to ACh (5.32 mM), DMPP (100 ${\mu}M$), McN-A-343 (100 ${\mu}M$) and high $K^+$ (56 mM). Fr. 4 - 5 itself did not affect basal CA secretion. Also, in the presence of Fr. 4 - 5 (60 ${\mu}g/mL$), the CA secretory responses to angiotensin II (AngII, 0.1 ${\mu}M$), veratridine (50 ${\mu}M$), Bay-K-8644 (10 ${\mu}M$), and cyclopiazonic acid (10 ${\mu}M$) were significantly reduced, respectively. In the simultaneous presence of Fr. 4 - 5 (60 ${\mu}g/mL$) and L-NAME (30 ${\mu}M$), the inhibitory responses of Fr. 4 - 5 on the CA secretion evoked by ACh, DMPP, high $K^+$, AngII, Bay-K-8644 and veratridine were considerably recovered to the extent of the corresponding control secretion compared with that of Fr. 4 - 5-treatment alone. The level of NO released from adrenal medulla after the treatment of Fr. 4 - 5 (60 ${\mu}g/mL$) was greatly elevated compared with the basal level. Taken together, these results demonstrate that Fr. 4 - 5 inhibits the CA secretion from the isolated perfused rat adrenal medulla evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of Fr. 4 - 5 is mediated by blocking the influx of $Ca^{2+}$ and $Na^+$ into the adrenomedullary chromaffin cells as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store, which is evoked at least partly through the increased NO production due to the activation of NO synthase. Based on these results, it is also thought that Fr. 4 - 5 isolated from $CH_2Cl_2$ extract of pine needle may contain beneficial antihypertensive components to prevent or treat hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.241-248
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• 2010

The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane-depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.

• Natural Product Sciences
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• v.27 no.2
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• pp.86-98
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• 2021

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K⁺, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and N^ω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na⁺ and Ca²⁺ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca²⁺ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT₁-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.

• The Journal of Internal Korean Medicine
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• v.35 no.4
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• pp.519-531
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• 2014

Objectives: Diabetic nephropathy is the most common cause of end stage renal disease. Transforming growth factor (TGF)-${\beta}1$, type IV collagen, advanced glycation end-products (AGEs), and angiotensin II type 1 receptor (AT1) are the main factors of diabetic nephropathy. We investigated the effects of Prunus on renal function and histopathological changes of diabetic nephropathy rat model induced by unilateral nephrectomy and streptozotocin. Methods: Diabetes was induced in male Sprague-Dawley rats ($290{\pm}10g$) by injecting streptozotocin (55 mg/kg) into the tail vein after unilateral nephrectomy. Rats were divided into 3 groups (n=6): normal, control, and Prunus. After 8 weeks of oral administration of Prunus extract on the Prunus group from 3 days after streptozotocin injection, we checked weight, 24 hrs urine, blood biochemistry and renal tissue to evaluate renal function and histopathological changes by examining parameters including albuminuria, BUN, creatinine, cholesterol, low density lipoprotein (LDL), triglyceride, TGF-${\beta}1$, type IV collagen, AGEs, and AT1. We also measured mRNA expression of TGF-${\beta}1$, type IV collagen, AGEs, and AT1 by Real Time polymerase chain reaction (RT-PCR). Results: Prunus decreased the amount of 24 hrs proteinuria, and inhibited histopathological changes of diabetic nephropathy including the expression and accumulation of TGF-${\beta}1$, type IV collagen and AGEs which could promote development of diabetic nephropathy. Prunus also inhibited mRNA expression of TGF-${\beta}1$, type IV collagen. Conclusions: These findings suggest that Prunus might protect the renal function and inhibit the development of renal injury by regulating factors including TGF-${\beta}1$, type IV collagen, AGEs, except AT1, so Prunus can be used for diabetic patients to prevent the progression of diabetic nephropathy.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.641-647
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• 2016

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high $K^+$ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-$N^G$-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.157-162
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• 2013

Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.565-572
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• 1997

In the freshly isolated rat nephron, the effect of endothelin-1, -2 and -3 (ET-1, -2 and -3) on cytosolic free calcium concentration ($[Ca^{2+}]_i$) was determined using the fluorescent indicator Fura-2/AM. $[Ca^{2+}]_i$ increase was investigated in 9 parts of the single nephron including glomerulus (Glm), $S_1,\;S_2,\;S_3$, cortical and medullary thick ascending limb and cortical (CCT) and outer medullary collecting tubule (OMCT). Endothelins increased $[Ca^{2+}]_i$ in Glm (ET-1; $127{\pm}17%$, ET-2; $93{\pm}5%$, ET-3; $169{\pm}17%$), CCT (ET-1; $30{\pm}6%$, ET-2; $38{\pm}19%$, ET-3; $158{\pm}18%$) and OMCT (ET-1; $197{\pm}11%$, ET-2; $195{\pm}11%$, ET-3; $215{\pm}37%$) at 10-7 M. In OMCT, ET-1 and ET-2 increased $[Ca^{2+}]_i$ in a dose-dependent manner ($10^{-10}{\sim}10^{-6}$ M). To the contrary, ET-3-induced $[Ca^{2+}]_i$ rise was begun from $10^{-12}$ M. BQ-123Na, an antagonist of ETA receptor, at $10^{-4}$ M inhibited about 30% of $[Ca^{2+}]_i$ rise induced by ET-1 and -3. Binding experiments using $[^{125}I]ET-3$ showed the existence of $ET_B$ receptor in OMCT. This binding was replaced by ET-1, ET-2 or ET-3 by the almost same degree but not by angiotensin II or vasopressin.

• Bulletin of the Korean Chemical Society
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• v.31 no.8
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• pp.2293-2298
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• 2010

Focused electrospray (FES) deposition method is presented for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. FES ion optics consists of two cylindrical focusing electrodes capped with a truncated conical electrode through which an electrospray emitter passes along the cylindrical axis. A spray of charged droplets is focused onto a sample well on a MALDI target plate under atmospheric pressure. The shape and size distributions of matrix crystals are visualized by scanning electron microscope and the mass spectra are obtained by time-of-flight mass spectrometry. Angiotensin II, bradykinin, and substance P are used as test samples, while $\alpha$-cyano-4-hydroxycinnamic acid and dihydroxybenzoic acid are employed as matrices. FES of a sample/matrix mixture produces fine crystal grains on a 1-3 mm spot and reproducibly yields the mass spectra with little shot-to-shot and spot-to-spot variations. Although FES greatly stabilizes the signals, the space charge due to matrix ions limits the detection sensitivity of peptides. To avoid the space charge problem, we adopted a dual FES/FES mode, which separately deposits matrix and sample by FES in sequence. The dual FES/FES mode reaches the detection sensitivity of 0.88 amol, enabling ultrasensitive of peptides by homogeneously depositing matrix and sample under atmospheric pressure.