• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.323-330
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

• Archives of Pharmacal Research
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• v.11 no.1
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• pp.65-73
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• 1988

The effects of clonidine on the negative chronotropic response induced by stimulation of vagus nerve were studied in the presence of propranolol in reserpinized and anesthetized rats. When the heart rate was decreased by stimulation of the vagus nerve, clonidine significantly inhibited vagally induced heart rate decrease (negative chronotropic response) in dose dependent manner. This inhibitory effect of clonidine was virtually abolished by phentolamine, ${\alpha}_1-\;and\;{\alpha}_2-adrenoceptor$ antagonist, and partially antagonized by prazosin, ${\alpha}_1-adrenoceptor$ antagonist. On the other hand, when the heart rate was decreased by the infusion of bethanechol, a muscarinic parasympathetic stimulant, clonidine had no effect on the bethanechol-induced heart rate decrease. These results suggest that clonidine inhibits vagally induced negative chronotropic response by activation of presynaptic ${\alpha}-adrenoceptors$ located on the parasympathetic cholinergic nerve terminal in the heart and this effect of clonidine is more related to ${\alpha}_2-adrenoceptors$ than ${\alpha}_1-adrenoceptors$.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.605-612
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• 2000

Background: Ischemic preconditioning enhances the tolerance of myocardium against ischemia/reperfusion injury, with the enhancement of the recovery of post-ischemic myocardial function. This study was disigned to assess whether the protective effect of ischemic preconditioning could provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rate heart. Material and method: Fourty four Spargue-Dawley rats, weighing 300~450gm, were divided into four groups. Group 1(n=7) and group 3(n=12) were subjected to 30 minutes of aerobic Langendorff perfusion without ischemic preconditioning and then preserved in saline solution at 2~4$^{\circ}C$ for 4 hours and 5 respectively. Group 2(n=7) and group 4(n=18) were perfused in the same way for 20 minutes, followed by 3 minutes of global mormothermic ischemia and 10 minutes of perfusion and then preserved in the same cold saline solution for 4 hours and 5 hours respectively. Heart rate, left ventricular developed pressure(LVDP), and coronary flow were measured at 15 minutes during perfusion as baseline. Spontaneous defibrillation time was measured after reperfusion. Heart rate, LVDP, and coronary flow were also recorded at 15 minutes, 30 minutes, and 45 minutes during reperfusion. Samples of the apical left ventricular wall were studied using a transmission electron microscope. Result: Time of spontaneous defibrillation(TSD) was significantly longer in group 4 than in group 1(p<0.001), and TSD in group 1 was significantly longer in comparision to that of group 2(p<0.05). Heart rate at 45 minutes was significantly higher in group 1 than in group 4(p<0.05). Heart rate at 15 min was significantly higher in group 2 than in group 1(p<0.001) and in group 4 than in group 3(p<0.05). Left ventricular developed pressure(LVDP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.01), LVDP at 45 minutes was higher in group 4 than in group 3(p<0.05). Rate-pressure product(RPP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.05). RPP at 15 minutes was higher in group 2 than in group 1(p<0.01). RPP at 30 minutes and 45 minutes was higher in group 4 than in group 3(p<0.05). Group 2 showed relatively less sarcoplasmic edema and less nuclear chromatin clearance than group 1. Group 4 showed less myocardial cell damage than group 3, group 4 showed less myocardial cell damage than group 3, group 4 showed more myocardial cell edema than group 1. Conclusion: Ischemic preconditioning enhanced the recovery of postischemic myocardial function after 4 hours and 5 hours preservation. However, it was not demonstrated that ischemic preconditioning could definitely provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rat heart.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.181-186
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• 2006

This study was undertaken to evaluate whether peroxisome proliferator-activated-receptor-gamma $(PPAR-{\gamma})$ agonist-rosiglitazone (ROSI) induces postischemic functional recovery in Langendorf heart model. Hearts isolated from normal rats were subjected to 20 min of normoxia or 25 min zero-flow ischemia followed by 50 min reperfusion. In this acute protocol, ROSI $(20\;{\mu}g/ml)$ administered 10 min before ischemia had no effect on hemodynamic cardiac function, but had protective effect on lipid peroxidation in in vitro experiments. In chronic protocol in which ROSI was given by daily gavage (4 mg/kg) for three consecutive days, ROSI could not prevent the hemodynamic alteration on cardiac performance, but has protective effect on the activity of superoxide dismutase (SOD). There was no significant difference in the contents of reduced glutathione (GSH) and catalase activity between ischemia-reperfusion (IR) and ROSI treated IR hearts. Although ROSI had no effect on hemodynamic factor, it had effect on antioxidant activity. Our results indicate that ROSI provides partial beneficial effects by inhibiting lipid peroxidation and/or recovering normal level of SOD activity in the ischemic reperfused heart.

• Proceedings of the Korean Biophysical Society Conference
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• 2001.06a
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• pp.67-67
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• 2001

Our previous studies showed that the relaxation defect of diabetic heart was due to the changes in the expressional levels of SR $Ca^{2＋}$-ATPase and PLB. In the diabetic heart contractile abnormalities were also observed, and one of the mechanisms for these changes could include alterations in the expression and/or activity levels of various $Ca^{2＋}$ regulatory proteins involving cardiac contraction.(omitted)

• Biomedical Science Letters
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• v.2 no.1
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• pp.71-90
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• 1996

There is considerable current interest in the effect of regular vigorous exercise and in particular endurance-running as a possible measure in improving myocardial function. Some data indicate that the aging heart may actually suffer from vigorous endurance exercise. On the contrary appropriate exercise in aged animals improves myocardial function and aerobic energy metabolism. So far there is relatively little data to indicate that endurance exercise is in fact beneficial in improving myocardial function or damaging to heart of aged animals. The present investigation aimed to study the possible effect of a long range treadmill training program on the heart in aging rats. Male rats aged 3, 10, and 20 months were divided at random into a control (sedentary) and an exercise group. The training group was exercised for 5 days a week on an automated treadmill for 20minutes at 18m/min over a period of 5 months. The exercise regimen of our experiments did not cause any significant changes in the tissues and ultrastructural as com-pared with sedentary age-matched control. Tissues and ultrastructures of myocardial cells in trained group aged 8 months are intact and well organized as well as sedentary control group. Age associated tissue and ultrastructural changes of trained group aged 15 months included : an increase in transformed mitochondria, vacuoles, lysosomes, lipid droplets and early lipofuscin. But the trained heart did not show significant difference in tissue and ultrastructural properties from those of sedentary controls. Endurance-trained group aged 25 months showed significant qualitative tissue and ultrastructural difference as compared with age-matched controls. In addition to those found in 25 months control group, focal necrosis, myofibril fraying, hypercontraction band, seperation of intercalated discs, degenerating nucleus and infiltration of collagenous fiber into myocyte were noted in trained 25 months group. The stereological examination of the mi-crographs disclosed no significant difference in the myoflbril, mitochondrion, sarcotubule and in-terstitium volume density and surface density of mitochondrial cristae and numerical density of mitochondria between trained and control group aged 8 and 15 months. In the trained 25 months group, significant increase in volume density of interstitium, lipofucsin granule were shown as compared to untrained age-matched control. On the other hand, significant decrease in mitochondrion volume density was shown. The myofibril volume density did not differ between trained and control group although trained group showed slight increase. From the data obtained a reduced mitochondria/myofibrils ratio was found in trained rat heart aged 25 months and there was no difference between trained and control rat aged 15 months. But a slight but not significant increase was found in the trained group aged 8 months as compared with same age control group. Such increase in the ratio in young animals is considered to be of great importance to cardiac pumping and adaptability. Whereas such adaptations don't seem to occur in aged heart muscle. This study proposed that repeated endurance exercise do not cause any significant qualitative and quantitative ultrastructural change of heart muscle in young(3months) and adult (10months) suggesting that the heart is able to adapt to the exercise. On the contrary, the repeated endurance exercise stress may actually induce degenerative changes in the aged heart muscle(20months).

• The Korean Journal of Pharmacology
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• v.8 no.2
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• pp.63-69
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• 1972

The effects of omission of buffers from Krebs-Ringer medium on contractile activity, membrane potentials and ATP content of electrically stimulated isolated rat atria were investigated. 1) Contractile status: A rapid and marked depression of the contractile activity of atria occurred when buffer-free medium was substituted for the normal Krebs-Ringer medium. 2) Electrical status: The omission of buffers from medium did not alter the resting or action potential magnitudes of atria. However, the action potential duration was on initial increase followed by a decrease in the buffer-free medium. 3) ATP concentration: The omission of buffers from medium resulted in a marked decrease in the ATP levels of atria. It has been also found in the present study that bicarbonate buffer plays an important role for the maintenance of the contractility and ATP levels of the heart. The contractile depression by the omission of buffers was not directly associated with electrical alterations in resting or action potentials of the heart. In the absence of bicarbonate-buffer, glucose no longer plays to maintain the contractile activity and the ATP levels of rat atria.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.231-236
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• 1999

This study was performed to examine 1) Whether hypothermic cardiac arrest produces myocardial HSP72 expression; 2) And if, whether it serves to protect the heart against the subsequent hypothermic arrest. In the present study, neonatal rats were placed in an icebath to induce hypothermia. To determine whether hypothermic cardiac arrest produces myocardial HSP72, experimental animals were subjected to 10-min hypothermic insult before the extraction of the heart. The intervals between the insult and extraction were 1 (1 HR), 4 (4 HR), 8 (8 HR), 24 (24 HR) or 72 (72HR) hours. A minimal amount of HSP72 was detected in control, 1 HR and 72 HR groups. In contrast, 8 HR and 24 HR groups showed a significant level of HSP72 expressions. To assess the cardioprotective effect of HSP72 against hypothermic cardiac arrest, we compared the proportion of recovery from the arrest between control and preconditioned (PREC) animals. Control animals were subjected to 20-min hypothermic insult, while PREC group was preconditioned by 10-min hypothermic insult 8 hours before the 20-min test hypothermic insult. Resuscitation rate from cardiac arrest induced by the 20-min hypothermic insult in PREC group was significantly higher than that in controls. These results suggest that the cardioprotective effect of hypothermic preconditioning is associated with an increase in HSP72 expression.

• Korean Journal of Veterinary Service
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• v.33 no.3
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• pp.309-312
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• 2010

This was conducted to determine the effects of body weight, organ weight, hematological values and biochemical parameters by L-carnitine in the ovariectomized (OVX) rats. The animals were divided into 4 groups. Intact group (n=10) received no treatment and operation. Sham group (n=10) received only sham operation and no treatment. OVX group (n=10) received operation and no treatment. OVX+Carn group (n=10) received operation and L-carnitine. Body weight was significantly lower in OVX+Carn group than in all other groups. Also, organ weight such as heart, liver, spleen and kidney was measured. The heart and spleen weight were significantly lower in the OVX+Carn group than in the Intact and Sham group. The liver weight in the OVX+Carn group was significantly differences in comparison with those in the other groups. Also, there was significantly differences in the organ weight of kidney between in the OVX+Carn group and in the other groups. The hematological values of WBC, RBC, MCV, MCH and MCHC were no significant differences in any other groups. The total cholesterol, triglyceride and high density lipoprotein decreased significantly in the OVX+Carn group as compared to those in the OVX group. But, there were no significant differences in low density lipoprotein in any other groups. We conclude that L-carnitine enhanced the body weight in the ovariectomized rats. Our findings suggest that L-carnitine may influence the process of absorption of fat in the ovariectomized rats.

• Restorative Dentistry and Endodontics
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• v.24 no.4
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• pp.657-665
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• 1999

The effects of application of mustard oil (MO), a small-fiber excitant and inflammatory irritant into the rat maxillary molar tooth pulp on arterial blood pressure and heat race, and electromyographic (EMG) activity of the jaw muscles were assessed in the anesthetized rats. In addition, Evans blue extravasation following pulpal MO application was measured. Application of MO into the tooth pulp produced a significant increase in mean arterial pressure and heat rate which gradually returned to baseline level. Application of MO into the tooth pulp induced a significant and short-lasting increase in EMG activity of digastric masseter and tongue muscle. Application of MO into the tooth pulp significantly increased the plasma extravasation of Evans blue dye. However, Application of mineral oil into the tooth pulp did not produce any significant changes in EMG activity of the digastric, masseter and tongue muscles, mean arterial pressure and heart rate, and plasma extravasation of Evans blue dye. These findings indicate that changes in arterial blood pressure, heart rate, jaw muscle activity and plasma extravasation accompanying noxious tooth pulp stimulation call be utilized as indirect measure of orofacial pain and inflammation.