• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.447-456
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• 2018

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) ($576{\mu}g/kg/day$) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor ($AT_2R$) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as $TNF-{\alpha}$, MCP-1, $IL-1{\beta}$, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via $AT_2R$.

• Analytical Science and Technology
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• v.33 no.2
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• pp.59-67
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• 2020

Nadolol is a β-blocker drug, which effectively manages hypertension and angina pectoris. Its chemical structure allows the formation of four possible stereoisomers. A coupled column high-performance liquid chromatographic (HPLC) system with UV and fluorescence detection was investigated for simultaneously determining four nadolol enantiomers in human plasma. The plasma samples were prepared using a convenient liquid-liquid extraction process and passed through HPLC. Nadolol was initially separated from the endogenous compounds or other impurities in human plasma on a Phenomenex silica column, and its enantiomers were resolved and determined on a Chirapak AD-H column. The developed HPLC method achieved an effective chiral separation and significantly eliminated endogenous compound interference. This optimal HPLC method was validated following FDA guidelines. The results showed good selectivity, linearity, accuracy (90.50 % - 105.27 %), and precision (RSDs < 9.52 %) for each enantiomer. This method was also successfully applied to determine nadolol enantiomers in the plasma samples of a healthy male volunteer (after orally administering 80 mg racemic nadolol), proving its suitability for nadolol stereoselective pharmacokinetic studies.

• Journal of Plant Biology
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• v.37 no.3
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• pp.271-276
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• 1994

The possibility that 1-aminocyclopropane-1-carboxylic acid (ACC)-uptake may be dependent on the H+-gradient established across the plsma membrane was tested in protoplasts isolated from 2.5 day old mungbean hypocotyls. The ACC-induced ethylene production was inhibited when the H+-gradient was collapsed by the treatment with carbonycyamide-p-trifluro-methoxy-phenylhydrazone (FCCP). Moreover, the treatment with o-vanadate, a specific inhibitor of plasma membrane H+-ATPase, caused the inhibition of ethylene production. The ACC-induced ethylene production was inhibited by the treatemnt with verapamil (Ca2+-channel blocker), or ethylene glycol-bis($\beta$-aminoethyl ether) N, N, N', N'-tetraacetic acid (EGTA) (Ca2+-chelator). In contrast, the ehtylene production was stimulated by the application of A23187 (Ca2+ ionophore). The inhibitory effect of EGTA in the ethylene producton was magnified in the presence of A23187. From these results, we suggest that the external Ca2+ influx to the cytosol resulted in the stimulatin of ACC oxidase activity after ACC-uptake resulting from a H+-gradient across the plasma membrane.

• 대한예방의학회:학술대회논문집
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• 1994.02b
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• pp.293-296
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• 1994

At the conclusion of a double-blinded, randomized clinical trial of propranolol hydrochloride, but before un blinding, the patients and clinic personnel were asked to guess the treatment group assignment of each patient. While 79.9% of the patients receiving propranolol correctly Identified their treatment group assignment, 57.2% of the patients receiving placebo incorrectly guessed that they were aiso in the propranolol group. No specific mechanism was identified to explain why more patients receiving propranolol were better able to guess' their group assignment. Clinic physicians correctly identified the group assignment of 69.9% of the patients receiving propranolol and 68.8% of the patients receiving placebo. Clinic coordinators correctly identified the group assignment of 67.1% of the patients receiving propranolol and 70.6% of the patients receiving placebo. For clinic personnel, heart rate level and heart rate change seem to be the mechanisms employed to Identify their patients' treatment assignment.

• Journal of Society of Preventive Korean Medicine
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• v.6 no.2
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• pp.86-94
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• 2002

Ligusticum Chuanxiong and its components were reviewed in terms of pharmacodynamic mechanisms. Three components of about 40 chemical components in Chuanxiong tetramethylpyrazine, ferulinolol and Butylidenephthalide have mainly been studied for its pharmacodynamic mechanisms which are focused on the increase in blood flow and anti-oxidative stress. The mechanisms for the effects of Chuanxiong on the increase in blood flow can be summarized as four ways, 1) anti-coagulation 2) blocker of ${\beta}1$ adrenergic receptor 3) cellular control of Ca++ level 4) collagen synthesis. Chuanxiong also showed the effectiveness on free radical-induced injury. It seems that its effectiveness is also related to the mechanisms for the increase in blood flow.

• Journal of the Korean neurological association
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• v.36 no.4
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• pp.318-321
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• 2018

We describe a 44-year-old woman with paresthesia, fatigue, and palpitation, 10 days after human papillomavirus (HPV) vaccination. The quantitative sensory test showed abnormal detection threshold in her foot. Tilt test result indicated postural orthostatic tachycardia syndrome. Symptoms were improved after immunomodulating therapy, pain control drug, and oral beta blocker medication. This is first case report for small fiber neuropathy and autonomic dysfunction after HPV vaccination in Korea.

• The Korean Journal of Pharmacology
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• v.22 no.1 s.38
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• pp.24-33
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• 1986

To ascertain the existence of various adrenoceptors involved in active transport of sodium in the frog skin and to delineate their physiological roles, the influence of various adrenergic agonists and antagonists on the potential difference (PD), short-circuit current (SCC) and total skin conductance (TSC) of the isolated frog skin of Rana nigromaculata were investigated. PD and SCC were determined with Ussing's technique. Drugs were administered to the serosal side of the skin. Experimental results were summarized as follows: 1. The responses to norepinephrine (NE, $6{\times}10^{-8}-6{\times}10^{-5})M$), phenylephrine (PE, $5{\times}10^{-6}-5{\times}10^{-4}M$) and epinephrine (Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$) were characterized by marked elevation of PD & SCC in dose-related fashion, but the maximal effect attained by Epi was less than those of NE and PE. 2. These increments of PD & SCC were significantly inhibited by prazosin $(2{\times}10^{-6}M)$, a speciflc ${\alpha}_1$-adrenoceptor blocker. The stimulatory effect on PD & SCC were completely abolished by phenoxybenzamine (PBZ, $3.3{\times}10^{-5}M$), an irreversible ${\alpha}$-adrenoceptor blocking agent. Furthermore, with a larger doses of Epi produced marked decline of PD & SCC after the PBZ pretreatment. 3. Isoproterenol (ISP), a ${\beta}$-adrenoceptor agonist, in concentrations ranging from $5{\times}10^{-7}$ to $5{\times}10^{-6}M$ produced dose-related decrease in PD & SCC, which could be abolished by pretreatment with propranolol $(4{\times}10^{-6}M)$, a specific ${\beta}$-adrenoceptor blocker. It was further noted that the effects of Epi on PD & SCC were markedly potentiated by Propranolol pretreatment. 4. Clonidine as well as guanabenz produced increases in PD & SCC and these effects were inhibited more specifically by prazosin pretreatment than by yohimbine. These results indicated that there exist in the frog skin two distinctive types of adrenoceptors, ${\alpha}$ and ${\beta}$, which roughly corresponds to those in mammals, and that the ${\alpha}$ type of adrenoceptors mediate the stimulation of PD & SCC, whereas ${\beta}$-adrenoceptors mediate the inhibition. However, based on evidence at hand, no conclusion could be drawn on the subtype of ${\alpha}$-adrenoceptors which is involved in the stimulation of sodium transport in the frog skin.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.327-332
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• 2001

In recent years, experimental evidence have been suggested that melatonin has either contractive or relaxing effects on the vascular smooth muscle in vitro. But the effect of melatonin on the cardiovascular system in vivo had been emphasized about the hypotensive effect. In this work, we found not only hypotensive effect but also hypertensive effect of melatonin in rats and attempted to determine the mechanism of these effects elicited by melatonin. Regadless of concentration, melatonin(0.002~5 mg/kg) produced increase in mean blood pressure (MBP) in 36% (54/150 cases) and decrease in mean blood pressure in 64%(96/150 cases). As a whole melatonin caused an increase or a decrease in MBP without compensatory decrease or increase in heart rate. The melatonin-induced hypertension was abolished by the pretreatment of phenoxybenzamine, a ${\alpha}$-adrenoceptor antagoninst. The melatonin-induced hypotension was abolished by the pretreatment of propranolol, a ${\beta}$-adrenoceptor antagonist, ODQ, a NO-sensitive guanylate cyclase inhibitor, or nifedipine, a L-type $Ca^{2+}$ channel blocker, but not by bilateral cervical vagotomy. The results indicate that melatonin-induced hypertension may be related to ${\alpha}$-adrenoceptor stimulation and melatonin-indued hypotension may be related to ${\beta}$-adrenoceptor stimulation, inhibition of $Ca^{2+}$ channel and/or activation of guanylate cyclase.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6109-6114
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• 2013

Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (${\pm}2.87$) months (95%CI: 13.62-24.88) in the BB group and 13.20 (${\pm}2.37$) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.219-231
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• 1995

Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.