• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.153-159
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• 2009

We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-${\beta}$ (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-${\beta}$ in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.

• Journal of Embryo Transfer
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• v.31 no.1
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• pp.33-38
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• 2016

In this study, to improve the in vitro development of various cells including cloned embryos, the effects that isoproterenol and melatonin have on in vitro development of porcine parthenogenetic oocytes were investigated. Parthenogenetic activation was induced with electrical stimulation, BSA and 6-DMAP treatment. $10^{-7}M$ of melatonin and isoproterenol ($10^{-10}$, $10^{-12}$ and $10^{-14}M$) were supplemented for in vitro maturation (IVM) and in vitro culture (IVC) medium, with different concentrations. When isoproterenol and melatonin were supplemented in IVM medium with different concentrations, there was no significant (P<0.05) difference of maturation rate in the treatment groups as well as in that of only melatonin. As isoproterenol and melatonin were supplemented in IVM medium with different concentrations, blastocyst rates of isoproterenol $10^{-12}M$ treatment group (37.1%) were significantly (P<0.05) higher than control group (26.0%). Isoproterenol and melatonin were supplemented in IVC medium with different concentrations, then the cleavage rate of $10^{-12}M$ isoproterenol treatment group (82.2%) was significantly (P<0.05) higher than the group that melatonin was only supplemented (70.9%). There was no difference of blastocyst rate between the treatment groups. When isoproterenol and melatonin were supplemented for IVM+IVC medium with different concentrations, the cleavage rate of $10^{-12}M$ isoproterenol treatment group (92.5%) was significantly (P<0.05) higher than the control group (82.8%) and the group that melatonin was only treated (81.6%). The blastocyst rate of $10^{-12}M$ as 45.6% was significantly (P<0.05) higher than control group (25.2%) and melatonin treatment group (31.2%). The cell number of blastocyst in $10^{-12}M$ isoproterenol treatment group $35.5{\pm}3.4$ was significantly (P<0.05) highest. The results of this study showed that the development rate of IVC when both isoproterenol and melatonin were supplemented was higher than when melatonin was only supplemented. Therefore, it is concluded that isoproterenol is rather effective in the activation of melatonin. $10^{-7}M$ melatonin and $10^{-12}M$ isoproterenol were considered suitable concentration.

• The Korean Journal of Pain
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• v.14 no.2
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• pp.186-192
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• 2001

Background: Epidural test doses containing epinephrine are an incomplete marker for the detection of inadvertent intravascular injection. Therefore, many investigators have attempted to find a more reliable marker as an alternative to epinephrine in adult patients anesthetized with enflurane. The present study was designed to test whether two different simulated intravenous test doses of isoproterenol could be used as a reliable marker for the detection of inadvertent intravascular injection in adult patients anesthetized with $O_2-N_2O$-enflurane. Methods: Forty healthy adult patients were anesthetized with 1% end-tidal enflurane and nitrous oxide after endotracheal intubation and were randomized to one of two groups according to the dose of isoproterenol. Group 1 and 2 (n = 20 each) received 3 ml of 1.5% lidocaine with 3 and 5 g isoproterenol intravenously, respectively, to simulate an intravascularly administered test dose. Heart rate (HR) and systolic blood pressure (SBP) were measured at 20-second intervals for 4 min after injection. Results: Mean maximal HR increases were $24{\pm}17$, $35{\pm}11$ bpm (P < 0.05), mean maximal SBP increases were $14{\pm}8$, $13{\pm}9$ mmHg and mean maximal SBP decreases $20{\pm}11$, $22{\pm}9$ mmHg following the IV injection of 3, $5{\mu}g$ isoproterenol, respectively. The incidence of hypotension was similar in both groups. Isoproterenol 3 and $5{\mu}g$ produced 75%, 100% sensitivity in the HR criteria ($\geq$ 20 bpm increase) and 60%, 70% sensitivity in the SBP criteria ($\geq$ 15 mmHg), respectively. Conclusions: These results indicate that based on the HR response, the epidural test dose containing $5{\mu}g$ isoproterenol to simulate an intravascular administration is a more reliable marker than $3{\mu}g$ isoproterenol in adult healthy patients during enflurane anesthesia.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.5
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• pp.653-658
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• 2000

To examine the effects of lipoic acid on metabolic response to a ${\beta}$-agonist, isoproterenol, in broilers, chicks were fed dietary lipoic acid at levels of 0 (control) or 50 mg/kg for 24 d. At 27 d of age, chickens were randomly selected. Isoproterenol dissolved in 0.9% saline was injected into the wing vein at a dosage of 2 mg per kg BW; then, blood samples were taken at 0, 10, 20, 30, 60, 90, 120, and 180 min. Amounts of plasma glucose, NEFA, triglyceride and total cholesterol were determined. Dietary lipoic acid reduced only plasma total cholesterol by 25%. Following isoproterenol injection, plasma glucose in both groups increased for 20 min; then, it returned to its basal concentration. In contrast, the maximal reductions in plasma NEFA and triglyceride in both groups (20 to 30 min) were confirmed by isoproterenol injection. In addition, while glucose returned to the basal level, plasma NEFA in the lipoic acid-treated chickens increased above the basal or control value during the 60 to 180 min post-injection. The present study suggests that the dietary administration of lipoic acid elicits fatty acid mobilization in ${\beta}$-adrenergic response to isoproterenol when the basal level of plasma glucose is maintained.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.1-10
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• 1982

In an attempt to delineate the role of beta-adrenoceptors found to be existing in the brain tissue in the central regulation of renal function, isoproterenol, a ${\beta}-adrenergic$ agonist, was administered directly into a lateral ventricle of the rabbit brain and the changes of renal function were observed. Also, the effects of propranolol, a specific ${\beta}-adrenergic$ blocking agent, and its influence upon the isoproterenol action were studied. Isoproterenol, in doses ranging from 5 to $50\;{\mu}g/kg\;i.c.v.$, elicited antidiuresis which seemed to be related to the decreased renal hemodynamics brought about by the systemic hypotension. With moderate doaes of $15\;{\mu}g/kg$ the antidiuresis was less prominent and there was a tendency toward natriuresis, but with higher doses the natriuretic effect became less evident, overrun by the systemic hypotension. Propranolol, $500\;{\mu}g/kg\;i.c.v.$, produced little effect on the renal function, but it eliminated the antidiuretic action of $50\;{\mu}g/kg$ isoproterenol i.c.v. and reversed it to a diuretic and natriuretic one, along with increases in renal plasma flow and glomerular filtration rate. The systemic hypotension also was markedly attenuated by propranolol pretreatment. Thus, it was evident that the renal action of i.c.v. isoproterenol was not blocked by propranolol and became explicit only when the hypotensive action of isoproterenol which seems to he propranolol-sensitive is removed. Various possibilities to account for this disparity in sensitivity were discussed. It is suggested from these observations that the central ${\beta}-adrenoceptors$ might also be involved in the regulation of renal function along with ${\alpha}-adrenoceptors$, though less significant than the latter.

• Applied Microscopy
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• v.27 no.2
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• pp.121-130
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• 1997

It has been demonstrated that majority of cells in the mammalian body such as myocytes and epithelial cells of skin and intestine respond to mechanical force or environmental factors and exhibit partial disruption of cell membrane, i. e., cell wounding, even in a physiological condition. Myocardial cells are rather apt to be wounded than other cells since they are definitely exposed to mechanical stress by contraction-relaxation and blood flow. However, the mechanism how myocardial cells protect themselves against cell wounding is not yet clarified. On this background, the present study was performed to elucidate whether albumin leakage is related to cell wounding and to assess whether diltiazem, a potent calcium channel blocker, is beneficial in isoproterenol-induced cell wounding in the heart. Hearts isolated from New Zealand White rabbits ($1.5\sim2.0kg$ body weight, n=20) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to bolus administration of isoproterenol and diltiazem as following order: $1.6{\mu}M$ isoproterenol at zero min (the beginning point): $16{\mu}M$ diltiazem at 20min; $1.6{\mu}M$ isoproterenol at 25min; $16{\mu}M$ isoproterenol at 45 min; $160{\mu}M$ diltiazem at 65 min; $16{\mu}M$ isoproterenol at 70 min. During all experiments, the left ventricular function was recorded, albumin leakage in the coronary effluents was analyzed by electrophoresis and Western blot, and myocardial cell membranes were examined by conventional transmission electron microscopy. Data were analyzed by t-test and linear regression test. Isoproterenol significantly increased the inotropic and chronotropic contractions, coronary flow, and frequency of arrhythmia, however, diltiazem did not influence on hemodynamics except decrease in the frequency of arrhythmia and a slight decrease in contractility. Isoproterenol also resulted partial disruption of myocardial cell membrane and inclose in albumin leakage, while diltiazem pretreatment showed number of electron-dense plaques in the cell membrane and a tendency of decrease in albumin leakage. These results indicate that albumin leakage may be an indirect index of cell wounding in the heart and diltiazem nay be beneficial to protect myocardial cells against isoproterenol-induced cell wounding. It is likely that diltiazem promotes resealing process of the cell membrane.

• The Korean Journal of Pharmacology
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• v.5 no.2
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• pp.141-148
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• 1969

The direct effect of isoproterenol on renal function, when given intravenously, is usually obscured by its potent hypotensive action. To obviate the latter action, isoproterenol was infused directly into one renal artery of the dog, the other kidney serving as a control for the general action. And following results were obtained. In the first series of experiments, the directic action of isoproterenol was ascertained. $1.0\;{\mu}g/kg/min$. reduced on both kidneys the urine flow, clearances of PAH and creatinine, as well as the amount of sodium excreted, but the effect was weaker on the experimental side than on contralateral side. With $0.1\;{\mu}g/kg/min$., two cases among 6 experiments showed marked diuresis, two cases no apparent effect, and another two marked antidiuresis on the experimental kidney, whereas the contralateral kidney exhibited antidiuresis in all cases. Further reducing the dose unmasked the diuretic action on the ,experimental kidney. In another series, the effects of isoproterenol on the blood flow distribution within the kidney and on sodium concentration gradient within the kidney tissue were observed. $0.05\;{\mu}g/kg/min$ isoproterenol markedly increased the medullary plasma flow and slightly increased total renal plasma flow and glomerular filtration rate, along with concomitant increase in the amount of sodium excreted and osmolar clearance, and decrease in reabsorption of free water. Sodium concentration gradient markedly decreased in the experimental kidney, reaching 2/3 of the value observed in the contralateral kidney at the papilla. It is thus concluded that isoproterenol exerts a diuretic action, when infused directly into a renal artery, and the mechanism of the action rests on its hemodynamic action, substantiated as the increase in glomerular filtration and in the medullary blood flow, resulting in washout of hyperosmolality produced by the coutercurrent multiplier system.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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• pp.79-83
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• 2006

We evaluated therapeutic and preventive properties of dehydroepiandrosterone (DHEA), a weak androgenic steroid, against isoproterenol-induced cardiomyopathy. The cardiomyopathy was induced by daily i.p. administration of isoproterenol to rats for five days. One group of rats were given with daily s.c. for 5 days during isoproterenol and the other group with daily s.c. DHEA for total 10 days, including 5 days before and during isoproterenol. The animals were killed after each treatment, and cardiac muscle failure was evaluated using histopathologic examination and biochemical indices. DHEA was found to reduce the damaged area and inhibit the elevation in the serum levels of glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), skeletal muscle creatine kinase (CK) and heart creatine kinase (CK-MB) induced by isoproterenol. We also assayed widely used oxidative stress parameters, including thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase and glutathion peroxidase (GPx). DHEA decreased the escalated level of TBARS and enhanced the anti oxidant defense reaction with an increase in Mn-SOD and Cu/Zn-SOD. On the other hand, the treatment with DHEA did not affect catalase and GPx activity. The present study indicates that DHEA has a therapeutic and preventive effect against isoproterenol-induced cardiomyopathy and its effects may depend largely on the increase in SOD activity.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.65-70
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• 1997

In order to investigate the effect of ANP on surfactant secretion from alveolar type II cell(AT II cell) during circulatory derangement in adult respiratory distress syndrome (ARDS), the secretion of surfactant from AT II cells was evaluated in purely isolated AT II cultures from rat lungs. For the simulation of sympathetic stimulation during circulatory derangement, primary AT II cultures were incubatedwith isoproterenol and IBMX. In this isoproterenol stimulated AT II cells, ANP were added in the media for the investigation of effect of ANP on surfactant secretion from AT II cells. For the evaluation of surfactant secretion, $[^3H]-methylcholine$ was incorporated and the level of radiolabelled choline chloride secreted from the cells was determined. As previously reported, isoproterenol and IBMX stimulated surfactant secretion from AT II cells. Isoproterenol showed synergistic increase of surfactant secretion with IBMX in AT II cells. In isoproterenol stimulated AT II cells, physiological level of ANP inhibited the secretion of surfactant in primary cultures of AT II cells. On the basis of these experimental it is suggested that, in association with ciculatory change during ARDS, increased secretion of ANP by the pulmonary edema, hypoxia and congestive heart heart failure might aggravate the symptoms of ARDS by reduction of surfactant secretion from AT II cells.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.33-40
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• 2001

The aim of present study was to define the cellular mechanisms underlying changes in delayed rectifier $K^+\;(K_{DR})$ channel function in isoproterenol-induced hypertrophy. It has been proposed that $K_{DR}$ channels play a role in regulation of vascular tone by limiting membrane depolarization in arterial smooth muscle cells. The alterations of the properties of coronary $K_{DR}$ channels have not been studied as a possible mechanism for impaired coronary reserve in cardiac hypertrophy. The present study was carried out to compare the properties of coronary $K_{DR}$ channels in normal and hypertrophied hearts. These channels were measured from rabbit coronary smooth muscle cells using a patch clamp technique. The main findings of the study are as follows: (1) the $K_{DR}$ current density was decreased without changes of the channel kinetics in isoproterenol-induced hypertrophy; (2) the sensitivity of coronary $K_{DR}$ channels to 4-AP was increased in isoproterenol-induced hypertrophy. From the above results, we suggest for the first time that the alteration of $K_{DR}$ channels may limit vasodilating responses to several stimuli and may be involved in impaired coronary reserve in isoproterenol-induced hypertrophy.