• Herbal Formula Science
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• v.17 no.2
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• pp.175-186
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• 2009

The vasorelaxant effect of an extract of Lophatherum gracile Brongn (ELB) and its possible action mechanism were ascertained in aortic tissues isolated from rats. ELB relaxed endothelium-intact thoracic aorta in a dose-dependent manner. However, the induced vascular relaxation was abolished by removal in endothelium of the thoracic aorta. Pretreatment of endothelium-intact vascular tissues with $N^G$-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-$\alpha$]-quinoxalin-1-one (ODQ) significantly inhibited vascular relaxation induced by ELB. Moreover, ELB significantly increased cGMP production in aortic tissues, which was blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of ELB was attenuated by tetraethylammonium (TEA), and glibenclamide. ELB-induced vasorelaxation was not blocked by atropine, propranolol, indomethacin, verapamil, and diltiazem. Taken together, the present study demonstrates that ELB dilates vascular smooth muscle via an endothelium-dependent NO-cGMP signaling pathway, which may be at least in part related with the function of $K^+$ channels.

• The Korean Journal of Physiology
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• v.26 no.1
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• pp.27-35
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• 1992

We used the whole cell patch clamp technique to examine the ionic basis for the tail current after depolarizing pulse in single atrial myocytes of the rabbit. We recorded the tail currents during various repolarizations after short depolarizing pulse from a holding potential of -70 mV. The potassium currents were blocked by external 4-aminopyridine and replacement of internal potassium with cesium. The current was reversed to the outward direction above +10 mV. High concentrations of intracellular calcium buffer inhibited the activation of the current. Diltiazem and ryanodine blocked it too. These data suggest that the current is activated by intracellular calcium released from sarcoplasmic reticulumn. When the internal chloride concentration was increased, the inward tail current was increased. The current was partially blocked by the anion transport blocker niflumic acid. The current voltage curve of the niflumic acid sensitive current component shows outward rectification and is well fitted to the current voltage curve of the theoretically predicted chloride current calculated from the constant field equation. The currents recorded in rabbit atrial myocytes, with the method showing isolated outward Na Ca exchange current in ventricular cells of the guinea pig, suggested that chloride conductance could be activated with the activation of Na/ca exchange current. From the above results it is concluded that a chloride sensitive component which is activated by intracellular calcium contributes to tail currents in rabbit atrial cells.

• The Korean Journal of Physiology
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• v.26 no.1
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• pp.15-25
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• 1992

In order to elucidate the properties of the background current whole cell patch clamp studies were performed in rabbit ventricular cells. Ramp pulses of ${\pm}80\;mV$ from holding potential of 40 mV(or 20 mV) at the speed of 0.8 V/sec were given every 30 sec(or 10 sec) and current-voltage diagrams(I-V curve) were obtained. For the activation of the background current isoprenaline, adenosine 3',5'-cyclic monophosphate(dBcAMP), guanosine 3',5'-cyclic monophosphate(cGMP), and $N^6$-2'-o-dibutyryladenosine 3',5'-cyclic monophosphate(dBcAMP) were applied after all known current systems were blocked with 2mM Ba, 1 mM Cd ,5 mM Ni, 10 ${\mu}M$ diltiazem, 10 ${\mu}m$ ouabain, and 20 mM tetraethylammonium(TEA). The conductance of background current in control was $0.65{\pm}0.69$ nS at 0 mV, its I-V curves was almost linear and reversed near 50 mV. When there was no taurine in pipette solution, isoprenaline hardly activated the background current but when taurine existed in pipette solution, isoprenaline activated the larger background current. Cyclic AMP or cyclic GMP alone had little effect on the activation of the background current, while cGMP potentiated cGMP effect. When the background current was activated with cGMP and cAMP, isoprenaline could not further increased the background current. The background current activated by isoprenaline depended on extracellular $Cl^-$ concentration and its reversal potential was shifted according to chloride equilibrium potential. The change of extracellular $Na+$ concentration had little effect on reversal potential of the background current activated by isoprenaline.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.1
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• pp.148-154
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• 2008

The butanol extract of Euonymus alatus (BEA) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pre-treatment of the endothelium-intact aortic tissues with $N^G-nitro-L-arginine methylester$ (L-NAME), and 1 H-[1,2,4]-oxadiazole- [$4,3-{\alpha}$]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by BEA, respectively. BEA-induced vascular relaxation was not blocked by glibenclamide, tetraethylammonium (TEA), indomethacin, atropine, propranolol, verapamil, and diltiazem, respectively. Moreover, BEA inhibits phenylephrine-induced vascular constriction in a dose-dependent manner. These results suggest that BEA relaxes vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling.

• YAKHAK HOEJI
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• v.32 no.6
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• pp.402-414
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• 1988

In order to clarify the receptor types and mechanisms underlying the positive inotropic effect of dopamine on the mammalian ventricular myocardium, the action potential, its first derivatives and isometric contraction of the rabbit papillary muscle were recorded using a force transducer and glass capillary microelectrodes filled with 3M KCl. The results were as follows; (1) In normal Tyrode solution, the contractile force was increased and duration of action potential was shortened with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (2) The dose-response curve was markedly shifted to the right by pretreatment with reserpine (5mg/kg i.p., 24hrs prior to the experiment). (3) In 19mM $K^+-Tyrode$ solution, the duration of action potential, maximum rate of rise (V_{max}) of action potential and overshoot were significantly increased with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (4) The inotropic effect of dopamine on the rabbit papillary muscle pretreated with reserpine was antagonized by atenolol ($10^{-6}M$), but not by phentolamine ($3{\times}10^{-6}M$). (5) In rabbit papillary muscle partially depolarized by 19mM $K^+-Tyrode$ solution, slow electrical response (calcium mediated action potential) as well as contraction were restored by dopamine ($10^{-4}M$); this restoration was blocked by calcium antagonists ($3{\times}10^{-5}M$ $LaCl_3{\cdot}6H_2O$, $3{\times}10^{-6}M$ diltiazem) or ${\beta}-adrenoceptor$ antagonist ($3{\times}10^{-6}M$ atenolol), but not affected by ${\alpha}-adrenoceptor$ antagonist ($10^{-5}M$ phentolamine, $3{\times}10^{-6}M$ yohimbine) or vascular dopaminergic receptor antagonist ($10^{-5}M$ haloperidol). The above results may be interpreted as that the positive inotropic effect of dopamine through both direct and indirect action are caused by increase in slow inward current ($Ca^{2+}$ influx into themyocardial cell), and the direct action is mainly due to the stimulation of ${\beta}-adrenoceptors$ in the rabbit papillary muscle.

• Journal of Veterinary Clinics
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• v.25 no.5
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• pp.391-395
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• 2008

An 8-year-old intact male Yorkshire cross dog (7.5 kg of body weight) was referred with the primary complaint of exercise intolerance and occasional syncope. Initial cardiological examination could not identify any abnormalities except mild mitral regurgitation. Exercise stress test revealed chronotrophic incompetence. Furthermore the 1 hr-digital event recording found the sudden onset of paroxysmal sinus tachycaridas (156-172 bpm) lasting few minutes and stopping abruptly. In addition, the tachycardia terminated by vagal maneuver and verapamil administration. Based on this finding, the case was diagnosed as sinoatrial reentrant tachycardia (SART). The dog was treated with diltiazem and enalapril. Although the dog still has exercise intolerance, no syncope has been observed after medication.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1166-1173
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• 2006

The aqueous extracts of Cortex Caryophylli (AEC) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pretreatment of the endothelium-intact aortic tissues with N$^G$_nitro-L-arginine methyl ester (L-NAME) or 1 H-[1,2,4]-oxadiazole-[4,3-${\alpha}$l-quinoxalin-1-one (ODQ) inhibited the relaxation induced by AEC. AEC-induced vascular relaxations were also markedly attenuated by addition of verapamil, diltiazem and glibenclamide, tetraethylammonium (TEA), respectively, while the relaxation effect of AEC was not blocked by indomethacin, atropine, or propranolol. Moreover, incubation of endothelium-intact aortic rings with AEC increased the production of cGMP. These results suggest that AEC dilates vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling, which seems to be causally related with L-type Ca$^{2+}$ and K$^+$ channels.

• Korean Journal of Clinical Pharmacy
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• v.31 no.1
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• pp.61-78
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• 2021

Background and Objective: The use of potentially inappropriate medications (PIMs) increases the risk of negative health outcomes, including drug-related admissions. Tools for structured medication review have been developed to ensure optimal medication use and safety. Here, we aimed to evaluate medication use review (MUR) tools for community-dwelling older patients. Methods: We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). We searched PubMed, Embase, and the Cochrane Library from 1991 to 2020, excluding tools that are specifically applied to hospitalized patients or nursing home residents. We identified the most common inappropriate medications, drug-disease interactions, drug-drug interactions and prescribing omissions presented among tools. Results: From among 9,788 identified reports screened, 60 met our inclusion criteria; finally, 27 were eligible for data analysis considering originality and up-to-dateness. Most tools presented explicit criteria (93%), and only one was specific to community-dwelling elderly. The most common PIM was tricyclic antidepressants. Use of diltiazem and verapamil in patients with heart failure and the combination of nonsteroidal anti-inflammatory analgesics and warfarin were the most frequent disease-specific PIM and drug-interaction, respectively. Conclusions: Although several medication review tools have been developed for older adults, specific guidelines for community-dwelling populations remain limited. Furthermore, the list of PIMs differed among available tools. In future, specific but integrating MUR tools need to be developed for clinical practice considering this population.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.125-133
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• 2022

Carbon monoxide (CO) is a known gaseous bioactive substance found across a wide array of body systems. The administration of low concentrations of CO has been found to exert an anti-inflammatory, anti-apoptotic, anti-hypertensive, and vaso-dilatory effect. To date, however, it has remained unknown whether CO influences atrial natriuretic peptide (ANP) secretion. This study explores the effect of CO on ANP secretion and its associated signaling pathway using isolated beating rat atria. Atrial perfusate was collected for 10 min for use as a control, after which high atrial stretch was induced by increasing the height of the outflow catheter. Carbon monoxide releasing molecule-2 (CORM-2; 10, 50, 100 μM) and hemin (HO-1 inducer; 0.1, 1, 50 μM), but not CORM-3 (10, 50, 100 μM), decreased high stretch-induced ANP secretion. However, zinc porphyrin (HO-1 inhibitor) did not affect ANP secretion. The order of potency for the suppression of ANP secretion was found to be hemin > CORM-2 >> CORM-3. The suppression of ANP secretion by CORM-2 was attenuated by pretreatment with 5-hydroxydecanoic acid, paxilline, and 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, but not by diltiazem, wortmannin, LY-294002, or NG-nitro-L-arginine methyl ester. Hypoxic conditions attenuated the suppressive effect of CORM-2 on ANP secretion. In sum, these results suggest that CORM-2 suppresses ANP secretion via mitochondrial K_ATP channels and large conductance Ca²⁺-activated K⁺ channels.

• The Korean Journal of Physiology
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• v.23 no.2
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• pp.237-252
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• 1989

Effect of a $Na^+$ gradient on $Ca^{2+}$ uptake was studied in isolated sarcolemmal vesicles of cat ileal longitudinal muscle. $Ca^{2+}$ uptake was markedly stimulated in the presence of an outwardly directed $Na^+$ gradient. External $Na^+$, monensin and A23187 abolished the $Na^+-dependent$ $Ca^{2+}$ uptake. Monovalent cations such as $K^+$, $Li^+$, $Rb^+$, $Cs^+$ and choline could not substitute for $Na^+$ in enhancement of $Ca^{2+}$ uptake. Divalent cations such as $Ba^{2+}$, $Sr^{2+}$, $Mn^{2+}$ and $Cd^{2+}$ but not $Mg^{2+}$ inhibited the $Na^+-dependent$ $Ca^{2+}$ uptake. Increase in external pH in the range of 6.0 to 8.0 stimulated the $Na^+-dependent$ $Ca^{2+}$ uptake. Amiloride inhibited the $Na^+-dependent$ $Ca^{2+}$ uptake at concentrations above 0.5 mM, whereas diltiazem or vanadate did not. The apparent Km of the $Na^+-dependent$ $Ca^{2+}$ uptake for $Ca^{2+}$ was 18.2 ${\mu}M$ and apparent Vmax was 689.7 pmole/mg protein/5 sec. Kinetic analysis of the $Na^+-dependent$ $Ca^{2+}$ uptake showed a noncompetitive interaction between internal $Na^+$ and external $Ca^{2+}$. The dependence of $Ca^{2+}$ uptake on internal $Na^+$ showed sigmoidal kinetics and Hill coefficient for internal $Na^+$ was 2.52. Inside positive membrane potential generated by imposing an inwardly directed $K^+$ gradient and valinomycin significantly stimulated the $Na^+-dependent$ $Ca^{2+}$ uptake. These results indicate that a $Na^+-Ca^{2+}$ exchange system exists in the sarcolemmal membranes isolated from cat ileal longitudinal muscle and it might operate as an electrogenic process.