• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.783-796
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• 1997

The relaxation induced by stimulation of the inhibitory non-adrenergic, non-cholinergic (iNANC) nerve is mediated by the release of iNANC neurotransmitters such as nitric oxide (NO), vasoactive intestinal peptide (VIP) and adenosine triphosphate (ATP). The mechanisms of NO, VIP or ATP-induced relaxation have been partly determined in previous studies, but the detailed mechanism remains unknown. We tried to identify the nature of iNANC neurotransmitters in the smooth muscle of guinea pig ileum and to determine the mechanism of the inhibitory effect of nitric oxide. We measured the effect of NO-donors VIP and ATP on the intracellular $Ca^{2+}$ concentration$([Ca^{2+}]_i)$, by means of a fluorescence dye(fura 2) and tension simultaneously in the isolated guinea pig ileal smooth muscle. Following are the results obtained. 1. Sodium nitroprusside $(SNP:10^{-5}\;M)$ or S -nitro-N-acetyl-penicillamine $(SNP:10^{-5}\;M)$ decreased resting $[Ca^{2+}]_i$ I and tension of muscle. SNP or SNAP also inhibited rhythmic oscillation of $[Ca^{2+}]_i$ and tension. In 40mM $K^+$ solution or carbachol ($(CCh:10^{-6}\;M)$-induced precontracted muscle, SNP decreased muscle tension. VIP did not change $[Ca^{2+}]_i$ and tension in the resting or precontracted muscle, but ATP increased resting $[Ca^{2+}]_i$ and tension in the resting muscle. 2. 1H-[1,2,4]oxadiazol(4,3-a)quinoxalin-1-one $(ODQ:1\;{\mu}M)$, a specific inhibitor of soluble guanylate cyclase, limited the inhibitory effect of SNP 3. Glibenclamide $(10\;{\mu}M)$, a blocker of $K_{ATP}$ channel, and 4-aminopyridine (4-AP:5 mM), a blocker of delayed rectifier K channel, apamin $(0.1\;{\mu}M)$, a blocker of small conductance $K_{Ca}$ channel had no effect on the inhibitory effect of SNP. Iberiotoxin $(0.1\;{\mu}M)$, a blocker of large conductance $K_{Ca}$ channel, significantly increased the resting $[Ca^{2+}]_i$, and tension, and limited the inhibitory effect of SNP. 4. Nifedipine $(1\;{\mu}M)$ or elimination of external $Ca^{2+}$ decreased not only resting $[Ca^{2+}]_i$ and tension but also oscillation of $[Ca^{2+}]_i$ and tension. Ryanodine $(5\;{\mu}M)$ and cyclopiazonic acid $(10\;{\mu}M)$ decreased oscillation of $[Ca^{2+}]_i$ and tension. 5. SNP decreased $Ca^{2+}$ sensitivity of contractile protein. In conclusion, these results suggest that 1) NO is an inhibitory neurotransmitter in the guinea pig ileum, 2) the inhibitory effect of SNP on the $[Ca^{2+}]_i$ and tension of the muscle is due to a decrease in $[Ca^{2+}]_i$ by activation of the large conductance $K_{Ca}$ channel and a decrease in the sensitivity of contractile elements to $Ca^{2+}$ through activation of G-kinase.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.901-913
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• 1989

This study was investigated under the postulation that activation of intracellular calcium- calmodulin complex during ischemia-reperfusion leads to myocardial injury. The protective effects of calcium channel blocker, diltiazem and calmodulin inhibitors, trifluoperazine, flunarizine and calmidazolium from ischemic injury in rat hearts were observed by using Langendorff apparatus when the antagonists were infused for 3 min in the beginning of ischemia. Thereby, an increase in resting tension developed during 30-min ischemia was analyzed with regard to [1] the degree of cardiac functional recovery following 60-min reperfusion, [2] changes in biochemical variables evoked during 30-min ischemia. The results obtained were as follows: l. In the ischemic group, the resting tension was increased by 4.1*0.2 g at 30-min ischemia. However, the increase in resting tension was markedly reduced not only by pretreatment with diltiazem [3.3 p M] but also with calmodulin inhibitors, trifluoperazine [3.3 p M], flunarizine [0.5 p M] and calmidazolium [0.5 p M], respectively. 2. Recovery of myocardial contractility, +dF /dt and coronary flow were much reduced when evoked by reperfusion in the ischemic group. These variables were significantly improved either by pretreatment with diltiazem or with calmodulin inhibitors. 3. The resting tension increment evoked during ischemia was significantly inversely correlated with the degree of cardiac function recovered during reperfusion. 4. Following 30-min ischemia, the production of malondialdehyde and release of lysosomal enzyme were much increased in association with a decrease in creatine kinase activity. 5. The increases in malondialdehyde production and release of free lysosomal enzyme were suppressed by pretreatment with calmodulin inhibitors as well as diltiazem. Likewise, the decrease of creatine kinase activities was prevented by these calcium antagonists. With these results, it is indicated that a increase in resting tension observed during ischemia has an inverse relationship to the cardiac function recovered following reperfusion, and further, the later may be significantly dependent on the degree of biochemical alterations occurred during ischemia such as decrease in creatine kinase activity, increased production of malondialdehyde and increased release of free lysosomal enzyme. Thus it is concluded that calmodulin plays a pivotal role in the process of ischemic injury.

• Journal of Chest Surgery
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• v.21 no.2
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• pp.291-298
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• 1988

The effect of Vanadate on the isometric contraction, membrane potential and intracellular calcium ion activities of rabbit myocardial cells were investigated, using calcium selective microelectrode, filled with neutral calcium ion carrier, ETH-1001. The resting tension, the membrane potential and the intracellular calcium ion activities were recorded in normal Tyrode solution and compared with those in the contracture induced by 10 mM Vanadate. The following results were obtained: 1. The dose-response relationship between the contraction of Vanadate and twitch tension showed near-maximum response in 5mM with no corresponding changes in action potential. 2. The resting tension increased up to the amplitude of a control twitch in 10mM Vanadate with resting membrane potential, hyperpolarized. 3. Increase in intracellular calcium ion activities proceeded the contracture by 10mM Vanadate which were restored to the control level in accordance with a decrease of intracellular calcium ion activities. 4. The amplitude of contractures by 10mM Vanadate were 90-120% of the control twitch tension in which the intracellular calcium ion activities were increased about 70 times from p Ca, 7.1 in the control to p Ca, 5.8 in contractures.

• The Korean Journal of Physiology
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• v.28 no.1
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• pp.61-70
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• 1994

A new method is used to record the actual shortening produced during the auxotonic activity of the sartorius (SAR), gastrocnemius (CAS) and rectus abdominis (RAB) muscles of a lizard Uromastix. The auxotonic twitch and tetanus records thus obtained were used for the first time to calculate the coefficient of linear shortening (COLS). This coefficient represent the relative Index between change in length $(\Delta\;L=L_0-L_1)$ and tension $({\Delta}P\;P_0-P_1)$ due to shortening at the steepest rising phase of the twitch and tetanus, recorded at resting length. In addition to this, maximum shortening $(S_{max})$ and auxotonic tensions were also determined at resting lengths of these muscles. The COLS was found to express the speed of shortening and auxotonic tensions are suggested to be of value to express the internal architecture of SAR, GAS & RAB muscles. The results are discussed in terms of contractile and elastic elements of the muscles alongwith the importance of shortening at resting lengths in skeletal muscles.

• Journal of Life Science
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• v.8 no.4
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• pp.373-380
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• 1998

A considerable change observed in X-ray diffraction during the muscle contraction was that the movement of myosin head and conformational change of contractile monecules were occurred in the muscle contraction. Time slice requires tension peak after the onset of stimulation and the height of tension peak depends on the number of twitch cycle. The intensity of I$_{11}$, I$_{10}$, 143${\AA}$ reflection is measured with 5ms time resolution and is recorded in isometric tension. The peak height of I$_{11}$ and 143${\AA}$ intensity is changed after the onset of a stimulation I$_{i}$, and the length of twitch is shortened by successive twitches in the case of stimulation TI$_{i}$. On the other hand, the peak height of I$_{11}$ and 215${\AA}$ intensity starts to decrease at the 1st twitch and remains constant at low peak hight without appreciable recovery during the contraction term. In the case of uccessive twitch stimulation, the myosin heads of muscle are once moved from their resting position and never returned to their initial position.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.7-12
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• 1990

Cyclobuxine D is a steroidal alkaloid, which was extracted from Buxus microphylla var. koreana Nakai. In our previous studies, we clarified several pharmacological actions of cyclobuxine D: an antiinflammatory action, hypotensive and bradycardiac effects, negative inotropic effects on the several smooth muscles and cardiac muscle. The present study was undertaken to elucidate possible mechanisms by protection of myocardial tells from ischemia and reperfusion induced derangement in cardiac function and metabolism by cyclobuxine D. For this purpose, the isolated rat heart was used. Rat hearts were perfused for 60 min under ischemia conditions in the presence and absence of cyclobuxine D and verapamil, and for 30 min under reperfusion conditions. Ischemia produced a marked decline in contractile force, an increase of resting tension, an immediate release of ATP metabolites and an accumulation of calcium in the left ventricle. Cyclobuxine D (100ng/ml) ameliorated the myocardial injury produced by ischemia.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.197-201
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• 1988

Effects of high concentration of KC1 and caffeine on cytosolic $Ca^{2+}$ level $([Ca^{2+}]_{cyt})$, measured simultaneously with muscle tension using a fluorescent intracellular $Ca^{2+}$ indicator fura 2, were examined in isolated smooth muscle of rat aorta. High $K^+$ (72.7 mM) solution induced sustained increase in both $([Ca^{2+}]_{cyt})$ and tension. In contrast to this, caffeine (20 mM) induced a rapid increase in $([Ca^{2+}]_{cyt})$ followed by a decrease to a level which was higher than the resting level. However, muscle tension showed only a transient increase followed by a decrease below the resting level. In a $Ca^{2+}-free$ solution, high $K^+-induced$ neither $([Ca^{2+}]_{cyt})$ nor tension, whereas caffeine induced a transient increase in both $([Ca^{2+}]_{cyt})$ and muscle tension. These results suggest that high $K^+-induced$ contraction in vascular smooth muscle of rat aorta is due to $Ca^{2+}$ influx whereas caffeine-induced contraction is due to $Ca^{2+}$ release from cellular store. Further, caffeine seems to have an additional effect to decrease the sensitivity of the contractile elements to $Ca^{2+}$.

• The Korean Journal of Physiology
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• v.14 no.2
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• pp.7-16
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• 1980

The effects of various inotropic interventions on the shape of the steady state length tension relation and the length-dependent activation process in cardiac muscle were studied. The influence of inotropic interventions upon the action potential was also observed. The range of varying muscle length was from the optimal length$(l_{max})$, where the active tension production is maximal, to 0.85 $l_{max}$. Changes in stimulus frequency or in external bathing Ca concentration constituted the inotropic interventions in this experiment. The papillary muscles were isolated from the rabbit right ventricles and perfused with $HCO-_3\;-buffered$ normal Tyrode solution which was aerated with $3%\;CO_2-97%\;O_2$ mixed gas and kept at $35^{\circ}C$. Resting Passive tension at $l_{max}$ was approximately 30% of the total tension and appeared from the muscle length of 0.90 $l_{max}$. The effect of stimulus frequency on the steady state level of developed tension was: As the stimulus frequency was increased from 0.1 to 0.5 Hz, there was little change in developed tension. As the frequency was increased further, to a value of about 3 Hz, tension increased steeply. Further increase of the frequency to 5 Hz had little additional effect on the developed tension. The length-tension curves for isometric peak tension became more steeper with the degree of potentiation by inotropic interventions. The relative steepness of the normalized length-tension curves where tension production was expressed as a percentage of maximal tension developed at $l_{max}$, varied inversely with the level of inotropic state and these curves were not superimposable one another. Thus at the stimulus frequency of 2 Hz or at the external Ca concentration of 8 mM, the relative decline in the developed tension for a given change in muscle length was considerably less than the decline observed at the frequency of 0.5 Hz or at the concentration of 2 mM Ca. Action potential duration was prolonged significantly as the frequency increased from 0.2 to 2 Hz, and this change in action potential duration was not observable on the changes in muscle length. There was a tendency of the hyperpolarization of membrane potential when the muscle length was shortened from $l_{max}$ to 0.95 $l_{max}$. These results support the hypothesis that there is a length-dependence of the activation process.

• Journal of Chest Surgery
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• v.16 no.3
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• pp.272-280
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• 1983

With respect to controversial opinions concerning the nitroglycerin effects on cardiac muscle the direct nitroglycerin actions were thoroughly studied in isolated papillary muscles, atrial preparations and coronary strips of rabbits. Isometric active tension of papillary muscles developed at $35^{\circ}C$ upon electric stimulation at a rate of 60/min, was not affected by nitroglycerin up to a concentration of 10mg/L Higher concentrations of nitroglycerin, however, reduced action tension progressively. This depression of mechanical activity is accompanied by a decrease in oxygen consumption as measured by means of a flow respirometer. Resting oxygen uptake, on the other hand, remained unchanged. Similarly active tension of spontaneously beating atrial preparations also declined at a nitroglycerin concentration of more than 10 mg/L, whereas the sinus frequency did not change up to 40 mg/L. In contrast, rabbit coronary strips are much more sensitive to nitroglycerin and relax in a range of 10-100 ug/L of nitroglycerin concentration. The results indicate that the pharmacologic effects of nitroglycerin in coronary disease are due to vascular actions, because the plasma levels of nitroglycerin attainable in human therapy are not sufficiently high to directly influence the myocardium.

• The Journal of Korean Physical Therapy
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• v.20 no.3
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• pp.61-68
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• 2008

Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.