• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.273-277
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• 2011

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 $mg{\cdot}kg^{-1}$) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immuno-blotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.181-186
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• 2006

A pharmacological inhibition of nitric oxide synthase (NOS) in rats produces vasoconstriction, renal dysfunction, and hypertension. The present study was aimed at investigating whether the methanol extract of Serous commixta cortex (MSC) ameliorates $N^G$-nitro-L-arginine methylester (L-NAME) induced hypertension in rats. Treatment of rats with L-NAME (10 mg/kg/day in drinking water, 5 weeks) caused a sustained increase in systolic blood pressure (SBP). Administration of MSC (100 or 200 mg/kg/day, p.o) significantly lowered the SBP in the L-NAME-treated rats and this effect was maintained throughout the whole experimental period. Moreover, ecNOS expression in aorta and kidney tissue from L-NAME treated rats was significantly restored dy administration of MSC. Furthermore, the impairment of acetylcholine (ACh)-induced relaxation of aortic rings in the L-NAME treated rats was reversed dy administering of MSC. The renal functional parameters including urinary volume, sodium excretion, and creatinine clearance (Ccr) were also restored by administering MSC. Taken together, the present study suggeststhat MSC prevents the increase in SBP in rats with L-NAME-induced hypertension, which may result from the up-regulation of the vascular and renal ecNOS/No system.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• Journal of Life Science
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• v.32 no.2
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• pp.175-188
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• 2022

Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IK_Ca channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI₂. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.1060-1065
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• 2002

LC20 phosphorylation and PKC α play an important role in modulation of contractile activity of smooth muscle. Besides, myosin phosphatase is also related with smooth muscle contraction in signaling pathways. We previously demonstrated that Crataegi Fructus inhibited phenylephrine-induced contraction and which might be implicated in nitrite formation(Son et al., 2002). In this study, we investigated the effects of butanol fraction of Crataegi Fructus(BFFC) on the localization of α-protein kinease C(PKC α) and myosin phosphatase subnits(MPs) in freshly isolated single ferret potal vein cells, and phosphorylation of LC20 during phenylephrine stimulation. In PKC α and MPs localization, BFFC blocked its translocation from the cytosol to the cell membrane by treatment of phenylephrine. BFFC have also dephosphorylated LC20 phosphorylation by phenylephrine stimulation under basal level, but no significant. These results indicate that the relaxation effect of BFFC is associated with inhibition of PKC α activation and MPs dissociation, and thus myosin phosphatase activity may be increased.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.249-254
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• 2008

The present study was undertaken to determine whether hypoxia influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Hypoxia significantly inhibited fluoride-induced contraction regardless of endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction suggesting that other pathway such as $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, hypoxia significantly decreased fluoride-induced increase of phospho-myosin-targeting subunit of myosin light chain phosphatase (pMYPT1). Interestingly, hypoxia didn't inhibit significantly phenylephrine-induced contraction suggesting that myosin light chain kinase (MLCK) activity or thin filament regulation is less important on the hypoxia-induced vasorelaxation in the denuded muscle than Rho-kinase activity. In conclusion, this study provides the evidence and possible related mechanism concerning the vasodilation effect of hypoxia on the agonist-specific contraction in rat aortic rings regardless of endothelial function.

• Korean Journal of Pharmacognosy
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• v.2 no.4
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• pp.163-172
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• 1971

This paper attempts to observe the histological structure of Korean Arisaema ringens $S_{CHOTT}{'s}$ rhizome, to identify it's constituent and to investigate the pharmacological action with it's alcohol extract. The results are : 1) The inner structure of rhizome on the transverse section is divided into external and internal tissues by the ring of intercellular secretary sac. Raphides of calcium oxalate contained in mucilage cell, collateral vascular bundle, are extremely similar to those contained in Pinellia ternata. 2) The organs of the pistillate Arisaema ringens are larger and more plentiful than those of the staminate Arisaema ringens. The sexual identification is easy in the flowering season. 3) The alkaloid is identified by Meyer reagent as white p.p.t. at pH 2 of sulfuric acid. 4) The saponin is indentified remarkably by means of foaming reaction, Lieberman-Burchard reaction and hemolytic reaction. 5) The effect of alcohol extract on the relaxation of the isolated intestine of the rabbit is remarkably shown at the concentration of $10^{-3}g/ml$. 6) The effect of alcohol extract on the isolated ractus muscle of the frog increases the constructive action of acetylcholine at the concentration of $10^{-3}g/ml$. 7) The effect of alcohol extract on the isolated heart movement of the frog is decreased remarkably at the concentration of $10^{-3}g/ml$. 8) The effect of alcohol extract on the blood pressure of the rabbit is decreased by an interavenous injection of $10^{-3}g/kg$.

• Korean Journal of Pharmacognosy
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• v.21 no.2
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• pp.163-172
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• 1990

These studies were conducted to investigate the effects of Tongkwan-San water extract on analgesic, sedatative, anti-inflammatory, blood pressure and vasodilating actions, the relaxing action of isolated ileums and actions on the contact dermatitis induced by picryl chloride and on the leakage of the dye into the peritoneal cavity. The results of these studies were summarized as follows: The analgesic effect of Tongkwan-San was noted. The prolongation of anesthetic time of Tongkwan-San was recognized. Spontaneous motilities of isolated ileum of mice were strongly suppressed by Tongkwan-San. It inhibited the contractions of isolated ileum of mice induced by acetylcholine and barium chloride and the contraction of isolated ileum of guinea-pig induced by histamine. Inhibition of the contact dermatitis induced by picryl chloride was recognized. Anti-inflammatory effects in the paw edema induced by histamine and dextran were significantly shown. The leakage of dye into the peritoneal cavity in mice was significantly inhibited. Hypotensive and vasodilating action due to vascular smooth muscle relaxation were noted in rats and rabbits.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.125-132
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• 1997

Our previous study showed that in vivo treatment of spontaneously hypertensive rats (SHR) with protopanaxatriol ginsenosides (PPT) reduces the blood pressure and inhibits the con- tractions induced by endothelium-derived contracting factor (prostaglandin endoperoxide ($PGH_2$) and superoxide anion) in aorta isolated from SHR. The aim of the present study is to examine whether PPT improves endothelial functions in the isolated thoracic aorta of SHR in vitro. Treatments of aortic rings with PPT, purified ginsenoside $Rg_1$ ($Rg_1$) or indomethacin normalized endotheliuln-dependent relaxation to acetylcholine, but not with protopanaxadiol ginsenosides (PPD) and purified ginsenoside Rb1 (Rb1). The effects of PPT were dose-dependent. PGH,- and oxygen free radical-inducted contractions in rat aorta without endothelium were inhibited by PPT or $Rg_1$, but not by PPD or $Rb_1$. Contractions induced by PGF2$\alpha$, U-46619, a stable thromboxane A2 agonist or KCI (60 mM) were not inhibited by PPT, $Rg_1$ or $Rb_1$. These findings demonstrate that PPT but not PPD scavenges the oxygen-derived free radicals and/or antagonize the effects of $PGH_2$ in the vascular smooth muscle and may explain the hypotensive effect of ginseng in the SHR.

• Korean Journal of Pharmacognosy
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• v.14 no.1
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• pp.30-38
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• 1983

These studies were conducted in an attempt to investigate effects of 'Daeshiho-Tang' on the blood vessels, activities of liver enzyme and excretory action of bile juice in serum of $CCl_4-intoxicated$ rabbits, glucose and total cholesterol levels in serum of alloxan-induced diabetic rabbits. The result of these studies were summarized as follows; 1. Hypotensive ind vaso-dilatating actions due to vascular smooth muscle relaxation were noted in frogs, rabbits and dogs. 2. GOT, GPT and total cholesterol in serum of $CCl_4-intoxicated$ rabbits showed significant depressive effects. 3. Significantly increased biliary secretary effect was noted in $CCl_4-intoxicated$ rabbits. 4. Glucose and total cholesterol levels showed markedly decraese in alloxan-induced diabetic rabbits. Considering the experimental studies results, it is suggested that 'Daeshiho-Tang' has therapeutic efficacy to treat febrile diseses and metabolic diseases.