• Journal of Chest Surgery
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• v.42 no.5
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• pp.576-587
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• 2009

Background: The up-regulation of the nitric oxide (NO)-cGMP pathway might be involved in the change of vascular reactivity in rats 3 days after they suffer acute myocardial infarction. However, the underlying mechanism for this has not been clarified. Material and Method: Acute myocardial infarction (AMI) was induced by occluding the left anterior descending coronary artery (LAD) for 30 min (Group AMI), whereas the sham-operated control rats were treated similarly without LAD occlusion (Group SHAM), The concentration-response relationships for phenylephrine (PE), KCl, acetylcholine (Ach) and sodium nitroprusside (SNP) were determined in the endothelium intact E(+) and endothelium denuded E(-) thoracic aortic rings from the rats 3 days after AMI or a SHAM operation. The concentration-response relationships of PE in the E(+) rings from the AMI rats were compared with those relationships in the rings pretreated with nitric oxide synthase (NOS) inhibitor $N{\omega}$-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. The plasma nitrite/nitrate concentrations were checked via a Griess reaction. The cyclic GMP content in the thoracic aortic rings was measured by radioimmunoassay and the endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by real time PCR. Result: The mean infarct size (%) in the rats with AMI was $21.3{\pm}0.62%$. The heart rate and the systolic and diastolic blood pressure were not significantly changed in the AMI rats. The sensitivity of the contractile response to PE and KCl was significantly decreased in both the E(+) and E(-) aortic rings of the AMI group (p<0.05). L-NAME completely reversed these contractile responses whereas indomethacin did not (p<0.05). Moreover, the sensitivity of the relaxation response to Ach was also significantly decreased in the AMI group (p<0.05). The plasma nitrite and nitrate content (p<0.05), the basal cGMP content (p<0.05) and the eNOS mRNA expression (p=0.056) in the AMI rats were increased as compared with the SHAM group. Conclusion: Our findings indicate that the increased eNOS activity and the up-regulation of the NO-cGMP pathway can be attributed to the decreased contractile or relaxation response in the rat thoracic aorta 3 days after AMI.

• Applied Microscopy
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• v.32 no.2
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• pp.91-105
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• 2002

Urea transport in the kidney is mediated by a family of transporter proteins that includes renal urea transporters (UT-A) and erythrocyte urea transporters (UT-B). The cDNA of five isoforms of rat UT-A, UTA1, UT-A2, UT-A3, UT-A4, and UT-A5 have been cloned. The purpose of this study was to examine the expression of UT-A (L194), which marked UT-A1, UT-A2 and UT-A4. Male Sprague-Dawley rats, weighing approximately 200 g, were divided into three group: control rats had free access to water, dehydrated rats were deprived of water for 3 d, and water loaded rats had free access to 3% sucrose water for 3 d before being killed. The kidneys were preserved by in vivo perfusion through the abdominal aorta with the 2% paraformaldehyde-lysine- periodate (PLP) or 8% paraformaldehyde solution for 10 min. The sections were processed for immunohistochemical studies using pre-embedding immunoperoxidase method and immunogold method. In the normal rat kidney, UT-A1 was expressed intensely in the cytoplasm of the inner medullary collecting duct (IMCD) cell and UT-A2 was expressed on the plasma membrane of the terminal portion of the shortloop descending thin limb (DTL) cells (type I epithelium) and of the long-loop DTL cells (type II epithelium) in the initial part of the inner medulla. Immunoreactivity for UT-A1 in the IMCD cells, was decreased in dehydrated animals whereas strongly increased in water loaded animals compared with control animals. In the short-loop DTL, immunoreactivity for UT-A2 was increased in intensity in both dehydrated and water loaded groups. However, in the long-loop DTL of the outer part of the inner medulla, immunoreactivity for UT-A2 was markedly increase in intensity in dehydrated group, but not in water loaded group. In conclusion, in the rat kidney, UT-A1 is located in the cytoplasm of IMCD cells, whereas UT-A2 is located in the plasma membrane of both the short-and long-loop DTL cells. Immunohistochemistry studies revealed that UT-A1 and UT-A2 may have a different role in urea transport and are regulated by different mechanisms.

• Journal of Life Science
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• v.21 no.10
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• pp.1415-1421
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• 2011

The purpose of this study was to identify the effects of an L-arginine supplementation and regular exercise training on NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1, eNOS and Ang II in the aortas of D-galactose (D-gal) induced aging rats. The male Strague-Dawley rats were treated with a D-galactose aging inducing agent; the D-gal injection (50 mg/kg) was given intraperitoneally for 12 wk. Experimental groups were divided into five groups: (1) Young control group (Y-Con, n=8), (2) Aging control group (A-Con, n=8), (3) Aging exercise group (A-Ex, n=8), (4) Aging exercise group with L-arginine supplementation group (A-Ex+A, n=8), and (5) Aging with L-arginine supplementation group (A-A, n=8). The exercise consisted of running on a treadmill for 60 min/day at 20 m/min for 6 day/wk, at 0% gradient for 12 wk. The L-arginine supplementation was given orally at a dose of 150 mg/kg/day for 12 wk. The findings of this study were as follows: 1. NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins in the aortas of D-gal induced rats were significantly increased, however, L-arginine supplementation and regular exercise resulted in a significant inhibition in the expression of NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins. 2. eNOS protein in the aortas of D-gal induced rats was significantly decreased, however, L-arginine supplementation and regular exercise resulted in a significant increase in the expression of eNOS proteins. In conclusion, the findings of the present study reveal that L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation for 12 wk increases anti-inflammatory effects by decreasing NF-${\kappa}B$, TNF-${\alpha}$, and iNOS protein expressions within the aortic tissue. In addition, L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation may prevent endothelial function by up-regulation of eNOS protein in the aortas of D-gal induced aging rats.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.343-351
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• 2001

This study was undertaken to investigate the mechanism of lipopolysaccharide (LPS) and nitric oxide (NO) as a regulator of vascular smooth muscle cell (VSMC) proliferation. VSMC was primarily cultured from rat aorta and confirmed by the immunocytochemistry with anti-smooth muscle myosin antibody. The number of viable VSMCs were counted, and lactate dehydrogenase (LDH) activity was measured to assess the degree of cell death. Concentrations of nitrite in the culture medium were measured as an indicator of NO production. LPS was introduced into the medium to induce the inducible nitric oxide synthase (iNOS) in VSMC, and Western blot for iNOS protein and RT-PCR for iNOS mRNA were performed to confirm the presence of iNOS. Inhibitors of iNOS and soluble guanylate cyclase (sGC), sodium nitroprusside (SNP) and L-arginine were employed to observe the action of LPS on the iNOS-NO-cGMP signalling pathway. LPS and SNP decreased number of VSMCs and increased the nitrite concentration in the culture medium, but there was no significant change in LDH activity. A cell permeable cGMP derivative, 8-Bromo-cGMP, decreased the number of VSMCs with no significant change in LDH activity. L-arginine, an NO substrate, alone tended to reduce cell count without affecting nitrite concentration or LDH level. Aminoguanidine, an iNOS specific inhibitor, inhibited LPS-induced reduction of cell numbers and reduced the nitrite concentration in the culture medium. LY 83583, a guanylate cyclase inhibitor, suppressed the inhibitory actions of LPS and SNP on VSMC proliferation. LPS increased amounts of iNOS protein and iNOS mRNA in a concentration-dependent manner. These results suggest that LPS inhibits the VSMC proliferation via production of NO by inducing iNOS gene expression. The cGMP which is produced by subsequent activation of guanylate cyclase would be a major mediator in the inhibitory action of iNOS-NO signalling on VSMC proliferation.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.37-45
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• 1981

The importance of thyroid hormones for the survival of rats in the cold is along-established fact. Hypothyroid animals are unable to survive in a cold environment. It was also reported that acute exposure of rats, guinea pigs and rabbits to cold produced an increased secretion of TSH and thereby thyroid hormone secretion within 10 to 30 min, but this increase of thyroid activity disappeared quite rapidly during warming. However, in human study no significant difference was found in the concentration of $T_4$, TSH and cortisol between summer and winter. But plasma $T_3$ concentration was increased significantly in winter in 56 adult men. On the other hand, it has been also known that catecholamines are important in the maintenance of body temperature of rat exposured to cold. Abundant evidences suggest that the sympathetic nervous system is involved in the activation of nonshivering thermogenesis and that thyroid hormone metabolism and secretion are influenced by catecholamines and consequently by the activity of the sympatheticadrenal system. Many of the metabolic effects of catecholamines are associated with an increase in the level of cAMP mediated through activation of adenylate cyclase which converts ATP to cAMP. Other studies have shown that thyroid hormones affect the amount of adenylate cyclase present in the adipose tissue. On the other hand. it was also reported that a particulate cAMP phosphodiesterase activity in fat cells was modulated by the action of thyroid hormones. The objective of the present study was to determine the interaction between thyroid activity and cyclic nucleotides during acute exposure to cold. Albino rats weighing around 200 g were used as the experimental animal. The room temperature group was kept at $25^{\circ}C$ and the cold-exposured group was kept at $4^{\circ}C$ for 1 week or 2 weeks. Each group was subdivided into three subgroups; control, KI, and MTU group. At the end of experiment the animals were etherized and blood was taken from abdominal aorta for $T_4,\;T_3$ and cyclic nucleotides. The determinations of $T_3,\;T_4$ and cyclic nucleotides were carried out with a radioimmunoassay(RIA) method. The results were summerized as followings. 1) A significant increase of thyroid weight was observed in rats exposured to cold for 2 weeks. Furthermore, in rats administered MTU while to exposure to cold the thyroid weight was also increased significantly. 2) After 2 weeks $T_3$ concentration in the plasma of cold-exposured rats was significantly increased in KI group and MTU group as well as in control group. On the contrary, after 2 weeks of cold exposure $T_4$ level was decreased in control group. 3) In the case of cyclic nucleotides, plasma cAMP was increased in the control group after 1 or 2 weeks of cold exposure. However, cAMP level in plasma was rather significantly decreased in KI group and MTU group as well as in control group.

• Journal of Nutrition and Health
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• v.35 no.1
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1055-1062
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• 2009

Magnolia obovata exhibit several beneficial effects including anti-oxidant effects. Magnolia obovata is used as a therapeutic agent to stop hemorrhages and a tonic to promoted health in Korean and Chinese medicine. The pharmacokinetic profiles of the main Magnolia obovata is still not accurately investigated. In present study, I examined the effects of water extracts of Magnolia obovata on atherosclerosis induced high cholesterol diet in rats in serum and abdominal aorta. A total of 3-week old 9 male rats of Sprague-Dawley were divided into 3 groups and fed with the basal diet (normal group), high cholesterol diet (atherosclerosis induced group) for 8 weeks, high cholesterol diet supplemented with water extracts of Magnolia obovata (Magnolia obovata group) for 2 weeks. And rats were sacrificed, serum lipid level, abodominal aortic anti-oxidant activities and lipid peroxide were measured. These results indicated that serum total cholesterol, LDL-cholesterol, triglycerides concentration significantly lower in Magnolia obovata group than high cholesterol diet group. But HDL-cholesterol concentration had significantly higher in Magnolia obovata group than high cholesterol diet group. In conclusion, Magnolia obovata controls of lipid level of hyperlipidemia and hypercholesterolemia, thus suppresses the proliferation of intima in endothelial cells, which is risk factors of atherosclerosis induced high cholesterol diet in rats. I consider as Magnolia obovata is worth to using as atherosclerosis treatment.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.123-129
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• 2009

Patent ductus arteriosus(PDA) is an abnormal shunt between the descending aorta and pulmonary artery through the incompletely closed ductus arteriosus and is the most common congenital heart defect in dogs. Recent human genetic studies found that a the gene mutation in transcription factor AP-2 beta(TFAP2B) was responsible for syndromic cases of PDA. Mutations in the TFAP2B gene are associated with certain congenital cardiac defects in humans that include PDA. In this study, we isolated the entire coding exons of canine TFAP2B gene for genetic screening in dogs with PDA. Analysis of the deduced amino acid sequence suggested that the canine TFAP2B are phylogenetically closer to the human TFAP2B(100% identity in amino acid sequence) than mouse and rat. In cTFAP2B gene screening, one single c.936+203G>A base change was found in affected Maltese dogs with PDA. However, further screening found the same base change in one unaffected control dog, suggesting this base change might be polymorphism. No other base changes were found in other dog breeds enrolled in this study. Because the base change was located in the intronic region and found in an unaffected control dog, TFAP2B might not be responsible for familial PDA in Malteses and sporadic cases of other dog breeds, although the gene promoter region should be investigated before reaching to this conclusion. A future study that may take this study further would be to collect more samples and to screen TFAP2B in various breeds of dogs with PDA and other various congenital heart defects.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.65-72
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• 1993

Ultraviolet light radiation (UVR) did not affect resting tension of isolated thoracic aortae of rats. In aortic rings contracted with phenylephrine, however, UVR produced contractile and relaxant responses in preparations with and without endothelium, respectively. The contractile response was dependent upon the duration $(10{\sim}320\;sec)$ of irradiation, while the relaxation was not. UVR-induced contractions in endothelium-intact rings were significantly potentiated by increasing the concentrations of phenylephrine from $10^{-7}M$ to $10^{-5}M$, and also by addition of $10^{-6}M$ acetylcholine, $10^{-7}M$ isoproterenol and $3.5{\times}10^{-8}M$ nitroglycerine. However, addition of $10^{-6}M$ phentolamine, or $10^{-7}M$ to $10^{-6}M$ LY83583 inhibited the contraction or reversed the contraction to a relaxation. In endothelium-removed preparations the UVR-induced relaxation was attenuated by increasing concentractions of phenylephrine, and by addition of isoproterenol, nitroglycerin, phentolamine or LY83583. These results suggest that UVR produces contractile and relaxant responses in rat thoracic aortae with and without endothelium, respectively, and that the contractile effect results from the inhibition of endothelium-derived relaxing factor (EDRF) release by UVR the inhibition of and/or is in part re-lated to some endothelium-derived contractile factors (EDCFs).

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.99-105
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• 2012

Objectives : Korean red ginseng and Morus alba L. are used as a traditional treatment for diabetes. This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM) ameliorates metabolic syndrome in fructose-fed rats. Methods : Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose (HF) diet alone for 8 weeks, with supplementation with MPM or rosiglitazone occurring during the final 6 weeks. Results : MPM and rosiglitazone, synthetic $PPAR{\gamma}$ agonist, treatment significantly prevented the increase in fasting serum glucose, leptin, triglyceride, and low density lipoprotein in the HF group when comparing with the control group. MPM and rosiglitazone also led to an increase in high density lipoprotein level in the HF group. The administration of MPM and rosiglitazone prevented the development of the metabolic disturbances such as impaired glucose tolerance, and blood pressure. MPM suppressed increased expressions of endothelin-1 (ET-1) in HF rat aorta. In addition, MPM significantly increased IR-${\beta}$ and PPAR-${\gamma}$ expression in muscle. Conclusions : Based on these results, we suggest that the administration of MPM improves metabolic syndrome through the alteration in lipid profiles and suppression of insulin resistant and blood pressure.