• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.235-241
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• 2000

We examined the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs upon isoproterenol (Iso)-induced cardiac hypertrophy in rats. Then, we tried to investigate the effects of sympatholytics to see if they can modulate the expression of ANP and BNP. In this study, RT-PCR technique was used to characterize the expression of ANP and BNP in right atrium (RA) and left ventricle (LV) of the hypertrophied rat heart. Histologic findings indicated that stimulation of ${\beta}-adrenoceptors$ with Iso for 5 days was sufficient to induce cardiac hypertrophy in rats. A continuous stimulation with Iso for 7 days resulted in an increase of the ANP and BNP expression in the LV and BNP expression in the RA. The increased expressions of ANP and BNP in the LV were slightly inhibited, and the increased expressions of BNP in the RA were markedly inhibited by a continuous treatment with propranolol, metoprolol, and clonidine for 7 days. Overall, our data present a differential expression of the natriuretic peptides in Iso-induced cardiac hypertrophy, and that the mechanisms involved in this differential ANP and BNP gene expression could be mediated via sympathetic nervous system.

• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.7-13
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• 2004

Severe hypertension (>180 mmHg) develops in spontaneously hypertensive rats (SHR) after 12 wk-old; however, it is not clear whether what kinds of molecular mechanism leads to altered cardiac performance following developmental stages in SHR. Also, although the effect of calcineurin (Cn) to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. Thus, we have examined i) body weight and blood pressure, ii) differences of expression and distribution of signaling molecules such as Cn, protein kinase B/Akt (PKB/Akt), and extracellular signal-regulated kinase (ERK) between SHR and their age-matched control Wistar-Kyoto (WKY) rats following developmental stages. In 16 wk-old SHR compared with WKY, 2-dimentional echocardiography showed cardiac enlargement and hypertrophy of left ventricle, significantly. Taken together, we suggest that Cn is associated with hereditary cardiac hypertrophy, the process being related to the molecular signaling mechanisms involving PKB/Akt and ERK.

• Archives of Pharmacal Research
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• v.18 no.5
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• pp.346-350
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• 1995

To assess the behavior of the various chemicals, such as ethylcholine axiridinium (AF54A), scopolamine and morphine, the chemicals were administered into eitheer rat or mice. And water maze tests were performed before and during drug administration. In AF64A-treated groups (3 nmol/each ventricle), the latencies to escape was significantly increased in both of the pretraining-and posttraining groups. In scopolamine-treatment (2mg/kg, sc) to the pretrained group, the latency to escape was significantly shortened after the acute administration of scopolamine. However in subscute treatment group with scopolamine, the latency to escape was significantly increased. In morphine-treated groups (10 mg/kg, ip), the subacute treatmment with morphine, the latency to escape was not ahcnged. The results indicate that each chemical induces the learning impariment. However the chrmical-induced learning impairment may have different characteristics upon the exposed chemical. Also the results suggest that both the motivation and the retrieval of memory might be impaired by AF64A.

• The Korean Journal of Physiology
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• v.11 no.2
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• pp.9-16
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• 1977

The present experiment was conducted to see whether or not several cardioactive agents influence the 'regenerative $Ca^{++}$ release' in the mechanically disrupted cardiac cells. The mechanically disrupted cardiac cells were prepared by the method of Kerrick and Best from the ventricle of rat. The tension development of the disrupted cardiac cells was measured with a mechanoelectric transducer (RCA 5734). The results were summarized as follows 1) 2 mM caffeine enhanced the regenerative $Ca^{++}$ release, whereas 2 mM Procaine inhibited the $Ca^{++}$ release as reported by other investigators. 2) Epinephrine at concentrations of $10^{-7},\;10^{-6}\;and\;10^{-5}M$ increased the regenerative $Ca^{++}$ release significantly but showed a poor dose response on the $Ca^{++}$ release. 3) Propranolol showed no effect on the regenerative $Ca^{++}$ release when studied alone. Furthermore, it showed no antagonistic effect on an increased regenerative $Ca^{++}$ release induced by epinephrine. 4) Other cardioactive agents such as acetylcholine, ouabain, isoproterenol and c-AMP at concentrations of $10^{-6}M$ showed no effect on the regenerative $Ca^{++}$ release. From the above results, it may be concluded that the cardioactive actions of these agents are not related directly to the process of regenerative $Ca^{++}$ release.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.874-878
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• 2008

Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.

• Korean Journal of Veterinary Research
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• v.47 no.1
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• pp.7-17
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• 2007

The left main descending artery (LMDA) of left coronary artery (LCA) in rats runs around the left side of conus arteriosus after arising from the aortic sinus and descends to the apex of heart with branching several branches into the wall of left ventricle (LV). The ligation site of LMDA for myocardial infarction (MI) is the 2~4 mm from LCA origin, between the pulmonary trunk and left auricle. The characteristics that rat heart has no interventricular groove on the surface and its coronary arteries run intramyocardially with branching several branches give the difficulty in surgery for MI which resulted in expected size. This study was aimed to elucidate the branching patterns of the left coronary artery for analysis of MI size and for giving the basic data to producing small MI intentionally in 2 male species that are widely used, Sprague-Dowley (SD) and Wistar-Kyoto (WKY), in the world. Red latex casting was followed by the microdissection in 27 and 28 hearts of SD and WKY male rats, respectively. The branching patterns of LMDA were classified into 3 major types and others based on the left ventricular branches (L). The Type I, Type II, Type III and others are shown in 55.6%, 22.2%, 14.8%, and 7.4% in SD, 60.7%, 10.7%, 7.1%, and 21.5% in WKY, respectively. The branching number of the first left ventricular branch (L1) that are distribute the upper one third of LV was 1.2~1.5, and its branching sites were ranging 0.9~2.1 ᒠfrom LCA origin. L2, the second left ventricular branch distributing middle one third of LV, was the number of 1.2~1.4 and branching out ranging 5.1~5.7 mm. L3, the third left ventricular branch of LMDA distributing lower one third of LV, was the number of 1~1.5 and branching out ranging 7.0~9.3 mm from LCA origin. The common branch of L1 and L2 was branched from LMDA with the number of 1.1, and its site was located in the distance of mean of 1.5 mm and 2.8 mm in SD and WKY, respectively. The common branch of L2 and L3 was branched from LMDA with the number of 1, and its site was located in the distance of mean of 7.2 mm and 2.9 mm in SD and WKY, respectively. The right ventricular branches (R) of LMDA were short and branched in irregularly compared with L. The number of 1~4 of R were branched from LMDA. With regarding to the distribution area of L and the ligation site for MI, moderate MI (25~35% of LV) might be resulted in 70.4% and 60.7% in SD and WKY rats. Small MI might be produced intentionally if the ligation would be located at the 4~6 mm from LCA origin in the left side of LMDA. These data wold be helpful to expect the size of MI and to reproduce of small MI, intentionally, in rat hearts.

• Applied Microscopy
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• v.23 no.2
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• pp.11-26
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• 1993

This experiment was performed to study the morphological responses of the pigment epithelial cell and the Bruch's membrane of the retina of rat following X-ray irradiation. Male rats were divided into normal and experimental groups. The heads of the rats, under sodium thiopental anesthesia, were exposed to 3,000 rads or 6,000 rads of radiation in a single dose, respectively. The source was a Mitsubishi Linear Accelerator ML-4MV. The target to skin distance was 80cm, and the. dose rate was 200 rads/min. The experimental groups were sacrificed on the 6th hour, 2nd and 6th day after X-ray irradiation. Under anesthesia, 1% glutaraldehyde-1% paraformaldehyde solution(0.1M Millonig's phosphate buffer, pH 7.3) was perfused through the left ventricle and ascending aorta. Pieces of the tissue taken from the posterior region of the retina were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde(0.1M Millonig's phosphate buffer, pH 7.3) and 1% osmium tetroxide(0.1M Millonig's phosphate buffer, pH7.3), and embedded in araldite mixture. The ultrathin sections contrasted with uranyl acetate and lead citrate were observed with JEM 100 CX-II electron microscope. The results were as follow; 1. The morphological changes of the pigment epithelial cells were not pronounced after exposure to 3,000 rads of X-ray. But on the 6th hour after exposure to 6,000 rads of X-ray, bulging nuclear membrane protruding into the cytoplasm and nuclear chromatin clumped into numerous masses along the nuclear membrane were observed. At the 2nd and 6th day post-irradiation, partial cytolysis or necrosis were seen. 2. The thickness of the Bruch's membrane of the experimental groups were increased in the time and dose range covered by this study, and splitting or diffusing basal laminae of the choriocapillary layer were observed frequently in the experimental group. Above results suggest that large amount(6,000 rads) of head irradiation induce direct hazardous effects on the pigment epitherial cells and Bruch's membrane of the retina of the rat, but pigment epithelial cells are more radioresistant than Bruch's membrane.

• Toxicological Research
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• v.4 no.1
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• pp.55-84
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• 1988

This study was carried out to investigate the teratological potential of azinphos-methyl in the rat fetuses and to establish the nature of the effects on organogenesis and intrauterine development. The Sprague-Dawley female rats (180-210g) without previous litter were used in this study. Azinphos-methyl dosages of 0.094mg/kg, 0.4mg/kg, 1.5mg/kg were selected based on the acute intragastric $LD_{50}$ of 15mg/kg in the rat. Azinphos-methyl in water (Treatment Group), non-treatment control (Negative Control), water control (Sham Control), were administered by oral route and aqueous solution of acetyl salicylic acid (Positive Control) was administered by gavage at rate of 10 ml/kg of body weight from day 6 through 15. The results obtained were summarized as follows. 1. Decreased body weight of dams was observed in animals treated with aspirin and azinphos-methyl 1.5 mg/kg from day 7 through 14. (P<0.01) 2. There was an apparent decrement in the absolute liver weight in the azinphos-methyl 1.5 mg/kg treated group (P<0.05). However, the absolute and relative kidney weight in aspirin group (P<0.05, P<0.01) and the absolute and relative ovary weight in aspirin, azinphos-methyl treatment groups (P<0.01, P<0.05) were increased. 3. Decreased protein contents of dam's liver was observed in the aspirin and high dose azinphos-methyl treated group of animals (P<0.01). 4. The number of male-female ratio per dam increased in azinphos-methyl 1.5 mg/kg group but there was an apparent decrement in the body weight of fetuses in aspirin and high dose azinphos-methyl group (P<0.01, P<0.05). Total immature and resorbed fetuses were increased in aspirin group and the number of dead fetuses were also increased in azinphos-methyl 1.5mg/kg treated group of animals. (P<0.01, P<0.05). 5. In soft tissue defects, diaphragmatic hernia in diaphragm, anophthalmia, enlarged olfactory bulb, hydrocephalus, absence of third and lateral ventricle in skull, hydronephrosis in kidney, atrophy of left ventricle wall, enlarged apex in heart were observed. Especially, defects of diaphragm, heart and eye ball showed peak incidences in the high dose azinphosmethyl and aspirin group. (P<0.01). 6. Variations in the ossification patterns of skull, sternebrae, tail, forelimbs and hindlimbs showed peak incidences in the aspirin and high dose azinphos-methyl group. (P<0.01). 7. In the developmental indices of offspring, the mortality of aspirin and azinphos-methyl 1.5mg/kg treated group was higher than that of negative control. And, there was an apparent decrement in the body weight of fetuses (P<0.01) and considerable differences were obtained in pivoting, development of fur, auditory function, vision, quadrupled muscle development and testes descent in aspirin and azinphos-methyl 1.5mg/kg group. (P<0.01).

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.381-390
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• 2013

The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-1${\beta}$, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain.

• The Korean Journal of Physiology
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• v.21 no.1
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• pp.13-22
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• 1987

Effects of synthetic atrial natriuretic peptide and furosemide on the cardiovascular and renal functions were examined in the freshwater turtle, Amyda japonica. Both atria and ventricle of turtle contained an immunoreactive atrial natriuretic peptide. Synthetic rat atrial natriuretic peptide (atriopeptin III) and turtle atrial extract caused a decrease in mean arterial blood pressure and the vasodepressor effect was dose-dependent. In hydrated turtles received either atriopeptin III or turtle atrial extract, no significant change in renal function was observed until 100 min except a slight natriuresis at 60 or 100 min after injection of 30 ug/kg atriopeptin III or atrial extract, respectively. However, furosemide, 2 mg/kg, caused marked diuresis, natriuresis and kaliuresis. In non-hydrated turtles, no significant change in renal function was observed until 6 hrs following injection of 30 ug/kg atriopeptin III. Plasma aldosterone decreased at 2 hr and increased at 24 hr after injection of atriopeptin III although plasma renin concentration did not change. But, furosemide caused persistent diuresis, natriuresis and kaliuresis. Additionally, plasma aldosterone and renin concentrations were significantly increased at 24 hrs after injection of furosemide. In conclusion, we suggest that the freshwater turtle may have an atrial natriuretic peptide in heart and vascular receptors for atrial natriuretic peptide, and that atrial natriuretic peptide is more important in the regulation of blood pressure rather than that of renal function in freshwater turtles. We also suggest that an increased plasma renin concentration caused by furosemide may not be due to the sodium concentration delivered to macula densa, but due to the dehydration caused by persistent diuresis and natriuresis.