• Advances in Traditional Medicine
• /
• 제10권4호
• /
• pp.278-287
• /
• 2010

The present study was undertaken to evaluate the protective effect of ethanol (EtAS), ethyl acetate (EAAS) and aqueous (AQAS) extracts of Argyreia speciosa (AS) roots against Isoproterenol (ISO)-induced myocardial infarction in rats. The animals were exposed to isoproterenol (200 mg/kg. s.c) twice at an interval of 24 hrs. Cardioprotective effect was assessed by observing ECG parameters, serum marker enzymes and histopathology of the heart. Pretreatment of EAAS, and EtAS (200 mg/kg) resulted in a significant (P < 0.001) increase in P wave, QRS complex and R-R interval, whereas heart rate, QT interval and cardiac cycle were maintained near to normal values. EtAS and EAAS showed significant (P < 0.05; P < 0.001) reduction in all the tested diagnostic markers compared to ISO treated group. Histological studies on the structural changes of heart tissue supported the protective activity of AS. The result suggest that treatment of AS prior to ISO has a significant role in protecting the animals from ISO induced myocardial infarction.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권3호
• /
• pp.203-217
• /
• 2019

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).

• 한국축산식품학회지
• /
• 제38권2호
• /
• pp.259-272
• /
• 2018

This study aims to investigate the protective effects of kefir against myocardial infarction induced by isoproterenol (ISO). The rats were randomly divided into 4 groups, each group consisting of 8 rats. The control group, the kefir group (5 mL/kg/d kefir administered to rats as intra-gastric gavage for 60 d), the ISO group (100 mg/kg ISO was administered to rats, s.c. on 61. and 62. d), and kefir+ISO group (5 mL/kg/d kefir was administered to rats intra gastric gavage for 60 days prior to ISO, 100 mg/kg in two doses on day 61 and 62). 12 h after the last ISO dose, all rats were decapitated and their blood samples were collected. Cardiac tissue was reserved for histopathological examination. creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides, total cholesterol,very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and glucose were measured by autoanalyzer, whole blood malondialdehyde (MDA), glutathione (GSH) and plasma advanced oxidation protein products (AOPP) levels were measured spectrophotometrically. It was determined that in the group of kefir+ISO, the levels of AST (p<0.001), CK (p<0.001), LDH (p<0.001), MDA (p<0.001) and AOPP (p<0.001) were decreased, while the GSH (p<0.05) increased, compared to ISO group. There were no significant changes in lipid profile and glucose levels between these two groups. In conclusion, by examining cardiac enzymes and histopathological changes in cardiac tissue, it can be concluded that the administration of kefir in myocardial infarction induced by ISO can protect the heart with its antioxidant characteristic and minimize the toxic damage created by ISO.

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권3호
• /
• pp.235-241
• /
• 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.

• Journal of Ginseng Research
• /
• 제37권3호
• /
• pp.273-282
• /
• 2013

The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure ($+dP/dt_{max}$) and minimal rate of developed left ventricular pressure ($-dP/dt_{max}$), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

• Biomaterials and Biomechanics in Bioengineering
• /
• 제2권4호
• /
• pp.225-235
• /
• 2015

Treatments for asthma are largely pharmaceutical, with some therapies also utilising alternative breathing techniques. The objective of both medical and alternative methods is to relax contracted airway smooth muscle (ASM). In normal subjects, tidal breathing- and deep inspiration-oscillations are believed to have a bronchodilatory effect. Similarly, application of length oscillations to isolated, contracted ASM also elicits muscle relaxation. As a means of investigating more-effective alternative treatment methods for contracted airways, we analyse the combined effects of bronchodilators and length oscillations on isolated, contracted ASM. The contractile state of the muscle tissue prior to treatment is of primary interest. Thereafter, the effect of applying a combination of small superimposed length oscillations with tidal breathing-like oscillations to ASM is studied alone and in combination with a common bronchodilator, isoproterenol (ISO). This work suggests that relaxation of isolated, contracted ASM following application of combined oscillations and ISO is larger than treatments of either combined oscillations or ISO alone. Further, the observed oscillation-associated relaxation is found to be amplitude- rather than frequency-dependent. This study gives additional insight into the role of oscillations and bronchodilators on contracted airways.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권1호
• /
• pp.75-84
• /
• 2023

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, βmyosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 ㎍/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A₂ (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy. Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ

• The Korean Journal of Physiology and Pharmacology
• /
• 제24권3호
• /
• pp.259-266
• /
• 2020

Cardiovascular diseases are the primary reason of mortality, among which myocardial infarction (MI) is the most dominant and prevalent. This study was considered to examine D-Limonene protective action against isoproterenol (ISO) induced MI. Wister male rats were dispersed into four groups. Normal and D-Limonene control group in which rats administered saline or D-Limonene. ISO control animals were administered saline for 21 days then challenged with ISO (85 mg/kg, subcutaneously) on 20th and 21st day for MI induction. D-Limonene pretreated group in which animals were pretreated with D-Limonene 50 mg/kg orally for 21 days then administered ISO on 20th and 21st day. MI prompted variations were assessed by myocardial infarction area determination, blood pressure (BP) alterations, cardiac injury biomarkers and inflammatory mediators measurements. For more depth investigation, both the apoptotic status was evaluated via measuring mRNA expression of Bcl-2 and Bax as well as mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signal transduction were investigated via Western blotting. MI group revealed significant infarcted area, blood pressure alterations, myocardial injury enzymes intensification together with inflammatory cytokines amplification. MI was associated with activation of MAPK-ERK signal pathway and apoptotic status within the myocardium. On the other hand, pretreated with D-Limonene demonstrated deterred infracted area, reduced myocardial enzymes, improved BP indices, lessened inflammatory levels. Furthermore, D-Limonene pretreatment caused a decline in MAPK proteins pathway and Bax relative mRNA expression, while intensifying Bcl-2 mRNA expression promoting that D-Limonene may constrain MI induced myocardial apoptosis. D-Limonene mitigated MI injury through MAPK/NF-κB pathway inhibition and anti-apoptotic effect.

• The Korean Journal of Physiology and Pharmacology
• /
• 제13권6호
• /
• pp.503-510
• /
• 2009

To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP), in the regulation of human gastric motility, we examined the effects of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high $K^+$ and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle in human stomach. Gastric circular smooth muscle showed regular spontaneous contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone in a concentration-dependent manner. High $K^+$ (50 mM) produced sustained tonic contraction, and ACh $(10\;{\mu}M)$ produced initial transient contraction followed by later sustained tonic contraction with superimposed phasic contractions. FSK, ISO and SNP inhibited high $K^+$-induced tonic contraction and also ACh-induced phasic and tonic contraction in a reversible manner. Nifedipine $(1\;{\mu}M)$, inhibitor of voltage-dependent L-type calcium current $(VDCC_L)$, almost abolished ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP, which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction in human stomach partly via inhibition of $VDCC_L$.

• The Korean Journal of Physiology and Pharmacology
• /
• 제11권5호
• /
• pp.207-213
• /
• 2007

This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.