BACKGROUND: Impairment of relaxing response and augmentation of contractile response to vasoactive substances have been reported in atherosclerotic arteries. These alterations in vascular reactivity are considered as an underlying mechanism for the development of acute vasospasm in atherosclerotic coronary artery. Recently, it has been reported that lysophophatidylcholine (LPC), an oxidative metabolite of low density lipoprotein causes this functional abnormality. However, the precise mechanism of LPC induced change of vascular reactivity is still uncertain. METHOD: In this study, to elucidate the underlying mechanisms of abnormal vascular reactivity in atherosclerotic coronary artery, we examined the effect of LPC on whole cell K+current using patch clamping technique in rabbit coronary smooth muscle cells. RESULTS: Application of LPC(1microM) showed dual effect on whole cell outward current which depends on the magnitude of test potentials. At relatively high depolarizing test potentials (> 10 mV), LPC increased amplitude of outward current which was blocked by Gd3+ not by iberiotoxin (100 nM) and TEA (1 mM). Reversal potential of this Gd3+sensitive, LPC-induced current was -9.7 +/- 0.6 mV. At less depolarizing test potentials (< 10 mV), LPC decreased whole cell K+currents in a dose dependent manner (from 0.01 to 10 microM) in the range of -30 mV to +0 mV. Half maximal inhibition of K+current was 1.509 microM at 0 mV test potential (n =5). Depolarizing holding potential (0 mV) prevented this LPC-induced inhibition of K+current. Steady state activation and inactivation parameters of K+current were significantly shifted to the positive direction by application of LPC (p < 0.01, n =8). Pretreatment of staurosporine (100 nM), a blocker of protein kinase C partially blocked LPC-induced decrease of K+currents. CONCLUSION: LPC-induced inhibition of voltage dependent K+current may explain abnormal vascular reactivity in atherosclerotic coronary artery.
Arteries ; Constriction ; Coronary Vessels ; Lipoproteins ; Lysophosphatidylcholines* ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Protein Kinase C ; Staurosporine ; Tea

BACKGROUND: Histamine, released from mast cells in atheromatous plaque, has been known to cause cardiac ischemia or sudden cardiac death in atherosclerosis patient. Previous reports have suggested that histamine induced coronary vasoconstriction was due to increase in IP(3) and DAG, which induce release of Ca2+ from SR and increase the Ca2+ sensitivity of contractile element via activation of PKC. Recently, it was reported that application of histamine cause depolarization of intestinal smooth muscle, which may contribute to histamine-induced contraction via augmenting Ca2+ influx through activation of Ca2+ channels. However, the underyling mechanism of histamine-induced depolarization and its contribution to the magnitude of coronary vasoconstriction are still uncertain. METHOD: To elucidate the underlying mechanism of Ca2+ influx change during histamine-induced vasoconstriction, we examined the effect of Ca2+ channel antagonist and PKC blocker on histamine-induced contractions, and then measured the effect of PKC antagonist on whole cell K+ current using patch clamping method in rabbit coronary smooth muscle cells. RESULTS: Application of histamine induced phasic and tonic constraction of coronary rings via activation of H(1) receptors. Pretreatment of Ca2+ channel antagonist (nifedipine, 1 microM) or PKC blockers (10 nM staurosporine and 10 microM Go6976) markedly inhibited histamine-induced tonic contraction, which suggest that the magnitude of tonic contraction depend on the Ca2+ influx. Application of 4-AP, a blocker of voltage-dependent K+ channels, increased resting tone of coronary rings, and combined treatment of nifedipine blocked this 4-AP induced increase of resting tone. Application of active analoge of DAG (1,2-DiC(8)) significantly inhibited the activity of voltage-dependent K+ current in single smooth muscle cell, meanwhile the inactive analogue of DAG (1,3-DiC(8)) has no apparent effect on the activity of voltage-dependent K+ current. Furthermore, pretreatment of calphostin C (1 microM), a blocker of PKC, diminished the 1,2-DiC(8)-induced inhibition of K+ current. CONCLUSION: PKC dependent inhibition of voltage-dependent K+ current may be responsible for the maintaining of histamine-induced tonic contraction in rabbit coronary artery.
Atherosclerosis ; Constriction ; Coronary Vessels* ; Death, Sudden, Cardiac ; Histamine ; Humans ; Ischemia ; Mast Cells ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Nifedipine ; Protein Kinase C ; Staurosporine ; Vasoconstriction

Cytosolic Ca2+ concentration of rat ventricular cells was measured under varying experimental conditions by using a fluorescent Ca2+ indicator, Fura-2. Resting [Ca2+]i of rat myocyte was 150 +/- 30 nM (n = 39), and this value was compatible with others. The Perfusion of cardioplegic solution significantly increased [Ca2+]i, and this effect was further augmented by hypothermia (p<0.05). Application of nifedipine (5 x 10(-7) M) to the perfusate or pretreatment of caffeine (10 mM) had no apparent effect on this cardioplegia-induced [Ca2+]i change. But Ni2+ (5 mM), an antagonist of Na+/Ca2+ exchange mechanism, prevented the [Ca2+]i change during cardioplegia (p<0.05). Magnitude of cardioplegia-induced [Ca2+]i increase was also dependent on the Ca2+ concentration of cardioplegic solution. These results suggest that Na+/Ca2+ exchange may play an important role in cardioplegia-induced [Ca2+]i change. To rule out the possibility whether the protective effect of hypothermic cardioplegia is due to the preservation of high-energy phosphate store or decreasing the transmembrane ionic fluxes by phase transition, we exhausted a energy store of cardiac cell by application of 2,4 dinitrophenol to the bath and measured its effect on [Ca2+]i change during cardioplegia. Hypothermic cardioplegia delayed the onset of [Ca2+]i increase and decreased its amplitude compared to those of normothermic cardioplegia. From the above results, hypothermic cardioplegia may protect the cardiac cells from ischemic insult by preserving a high-energy phosphate store. Application of Ni2+ to the cardioplegic solution or reduction of external Ca2+ concentration also had some protective effect, since it prevented [Ca2+]i increase during cardioplegia.
Animal ; Calcium/*metabolism ; Cytosol/metabolism ; *Heart Arrest, Induced ; Heart Ventricle/metabolism ; Hypothermia, Induced ; Myocardial Ischemia/metabolism/*prevention & control ; Myocardium/*metabolism ; Rats ; Support, Non-U.S. Gov't

Isoproterenol (ISO), a beta agonist, causes hyperpolarization of coronary smooth muscle cells via an increase in K+ conductance. This hyperpolarization may cause the coronary vasorelaxation by decreasing the cytoplasmic Ca2+ concentration. It is well known that the activation of beta adrenoreceptors stimulates the adenylate cyclase activity, and the resulting K+ channel phosphorylation by cAMP-dependent protein kinase may be responsible for ISO-induced increase in K+ channel activity. However, it is not clear whether the increase in K+ channel activity by ISO is exclusively due to the activation of adenylate cyclase or not. In this research, the effect of ISO on the isometric tension and the mechanism of ISO-induced K+ channel activation were investigated in various patch clamp conditions. The summarized results are as follows. ISO- and pinacidil induced vasorelaxation was significantly inhibited by the application of TEA or by increasing the external K+ concentration. In the whole cell clamp mode, application of ISO increased K+ outward current, and this effect was completely eliminated by propranolol. In the cell-attached patch, application of ISO or forskolin increased Ca(2+)-activated K+ channel activity. Application of ISO to the bath in the outside-out patches or GTP in the inside-out patches stimulated Ca(2+)-activated K+ channels. From the above results, both A-kinase dependent channel phosphorylation and direct GTP-binding protein mediated effect might be responsible for the the activation of Ca(2+)-activated K+ channel by ISO in rabbit coronary smooth muscle cells. And this K+ channel activation also contributes to the ISO-induced vasorelaxation.
Animal ; Calcium/*metabolism ; Coronary Vessels/*drug effects/physiology ; Cyclic AMP-Dependent Protein Kinases/physiology ; Female ; GTP-Binding Proteins/physiology ; Isoproterenol/*pharmacology ; Male ; Muscle, Smooth, Vascular/*drug effects/physiology ; Potassium Channels/*drug effects ; Rabbits ; Support, Non-U.S. Gov't ; Vasodilation/drug effects

To elucidate the Ca2+ release mechanisms in the rabbit coronary artery, arterial preparations were permeabilized with beta-escin and changes in tension were measured under varying experimental conditions. Additionally, we investigated properties and distribution of two kinds of Ca2+ release mechanisms, Ca2+-induced Ca2+ release (CICR) and IP3-induced Ca2+ release (IICR). The results obtained were summarized as follows; 1. When a rabbit coronary artery was incubated in a relaxing solution containing 30 microM beta-escin for 40 min. sensitivity to externally added Ca2+ was much higher in beta-escin permeabilized muscle than in intact preparations. The contractile effect of IP3 in beta-escin permeabilized muscle was also demonstrated; 2. Caffeine and IP3 contracted coronary arteries were permeabilized with beta-escin, but the amplitude of contraction was much larger in the presence of caffeine than of IP3. 3. Intracellular heparin completely inhibited the contractions induced by IP3, but not those by caffeine. On the other hand, procaine inhibited the responses to caffeine, but not those to IP3. Ryanodine inhibited both the caffeine- and IP3-induced contractions. 4. The amplitude of contractile responses was much larger to the maximal stimulation of CICR by applying caffeine than to the maximal stimulation of IICR by applying IP3. After the maximal CICR stimulation by caffeine, the activation of IICR by IP3 without the reloading of Ca2+ could no longer evoke contraction. On the other hand, after the maximal IICR activation, the activation of CICR could still evoke contraction although the amplitude of the contraction was smaller when compared with the case without the initial IICR stimulation. 5. Acetylcholine contracted coronary artery smooth muscles were permeabilized with beta-escin. However, in the absence of added guanosine triphosphate (GTP), the responses were very small. Acetylcholine-induced contraction was inhibited by heparin, but not by procaine. From the above results, it may be concluded that there are two kinds of mechanisms of Ca2+ release, CICR and IICR, in the rabbit coronary artery smooth muscle cell. Also, whereas the CICR mechanism distributes on the membrane of the whole smooth muscle Ca2+ store, the IICR mechanism distributes only on a part of it.
Animal ; Arteries/metabolism ; Calcium/*metabolism ; Capillary Permeability/drug effects ; Coronary Vessels/drug effects/*metabolism ; Escin/pharmacology ; In Vitro ; Intracellular Membranes/*metabolism ; Rabbits ; Support, Non-U.S. Gov't ; Tissue Distribution

No abstract available.
Anthropology, Cultural ; Female ; Genital Diseases, Female/epidemiology* ; Genital Diseases, Female/etiology ; Genital Diseases, Female/therapy ; Human ; Korea ; Medicine, Traditional*

To elucidate the possibility whether an elevation of intracellular Ca2+ concentration ([Ca2+]i) in rabbit coronary artery myocytes during ischemic cardioplegic period may serve as one of the mechanisms of the "no-reflow' phenomenon or not, the changes in [Ca2+]i were measured under ischemic cardioplegia conditions using a fluorescent Ca2+ indicator, fura 2/AM. When single cells were perfused with cardioplegic or ischemic cardioplegic solutions, [Ca2+]i was significantly increased and the degree of [Ca2+] elevation was further augmented by the ischemic cardioplegic solution. Pretreatment of a sarcoplasmic reticulum emptying agent, 20 mM caffeine, had no effect on ischemic cardioplegia-induced [Ca2+]i changes, but application of a Ca2+ channel blocker, 5 x 10 (-1)M nifedipine, or an antagonist of Na+/Ca2+ exchange, 5 mM Ni2+, significantly inhibited the [Ca2+]i elevation, respectively. The magnitude of ischemic cardioplegia-induced [Ca2+]i elevation was dependent on the Ca2+ concentration of perfusate in the range of 0 and 25 mM. When Ni2+ was added to the reperfusion solution, recovery of ischemic cardioplegia-induced [Ca2+]i elevation was very rapid compared with the controls. It is concluded that ischemic cardioplegia-induced [Ca2+]i elevation may serve as one of the mechanisms of the "no-reflow' phenomenon in rabbit coronary artery smooth muscle cells. We propose that Na+/Ca2+ exchange may serve as a key function in ischemic cardioplegia-induced [Ca2+]i elevation.
Animal ; Arteries/metabolism ; Calcium/*metabolism ; Coronary Vessels/*metabolism ; Female ; *Heart Arrest, Induced ; Intracellular Membranes/*metabolism ; Male ; Muscle, Smooth, Vascular/*metabolism/pathology ; Myocardial Ischemia/*metabolism/pathology ; Osmolar Concentration ; Rabbits ; Support, Non-U.S. Gov't

Mastoparan is an amphiphilic tetradecapeptide derived from wasp venom which activates G-proteins. Several secondary effects have been attributed to this peptide, including activation of phospholipase and phosphatidylinositol kinase. The aim of the present study was to investigate the effects of mastoparan on vascular contractility. Rabbit aortic rings were cut and mounted on a force transducer to record isometric tension on a polygraph. The effects of mastoparan were then investigated on the contractile responses in the isolated rabbit aorta with or without endothelium. The results were summarized as follows; 1. Mastoparan caused biphasic response, a transient relaxation followed by a further contraction, in norepinephrine (NE)-precontracted ring with endothelium. These effects were not observed in the aorta in the absence of endothelium. 2. Mastoparan-induced transient relaxation was significantly inhibited by treatment with a N-omega-nitro-L-arginine or methylene blue. 3. When an inhibitor of phospholipase C, neomycin was added to the precontracted aortic ring with NE, the transient relaxation induced by mastoparan was inhibited, but sustained contraction was not inhibited. 4. When an inhibitor of phospholipase A2, quinacrine and inhibitor of the cyclooxygenase pathway, indomethacin, were added to a precontracted ring with NE, the transient relaxation induced by mastoparan was not inhibited, but sustained contraction was inhibited. 5. Mastoparan induced a contraction of the aorta either with or without endothelium. Indomethacin and nifedipine inhibited mastoparan-induced contraction. From the above results, we concluded that mastoparan acts on the endothelium and modifies the release of endothelium-derived relaxing factors such as nitric oxide and also endothelium-derived contracting factors such as metabolites of arachidonic acid.
Animal ; Aorta/*drug effects/physiology ; Arginine/analogs & derivatives/pharmacology ; Calcium/metabolism ; In Vitro ; Indomethacin/pharmacology ; Neomycin/pharmacology ; Nitroarginine ; Quinacrine/pharmacology ; Rabbits ; Support, Non-U.S. Gov't ; Vasoconstriction/*drug effects ; Wasp Venoms/*pharmacology

OBJECTIVES: Our purpose was to determine the efficacy of maternal corticosteroid therapy in the prevention of neonatal respiratory distress syndrome. STUDY DESIGN: The data in this study was taken from 136 women who participated in prematurity prevention programs at two hospital. Of 136 women who were delivered at 25 to 34 weeks, 68 received dexamethasone and 68 did not. 'I'he frequency and relative risk of adverse outcomes, including repiratory distress syndrome, necrotizing enterocolitis, neonatal sepsis and maternal infection wcre compared by means of univariate techniques. RESULT: When dexamethansone was administered, there was a lower incidence of respiratory distress syndrome at between 30 to 32 weeks gestation (relative risk of treatment group vs control group=0.425, p<0.05) and there was no statistical difference between 24 to 26 weeks (relative risk of treatment group vs control group=0.833, p>0.05). I'here was no statistical difference between 33 weeks to 34 weeks (relative risk of treatment group vs control group=0.782, p>0.05). 'I'here was no statistical significance in the incidence of maternal infection, neonatal sepsis or necrotizing enterocolitis (p=0.808, p=0.698, p=0.559). CONCLUSION: Dexamethasone appears to significantly reduce neonatal respiratory distress syndrome at between 30 and 32 weeks gestation.
Dexamethasone ; Enterocolitis, Necrotizing ; Female ; Humans ; Incidence ; Pregnancy ; Respiratory Distress Syndrome, Newborn* ; Sepsis

A prospective study was initiated to compare maternal serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies. Serum specimens were obtained from 87 women with a normal intrauterine pregnancy and 47 women with abnormal pregnancies which were ended in spontaneo abortion or pathologically confirmed to be missed abortion. In normal pregnancies, the mean serum CA-125 concentrations were increased significantly from amenorhea 6 weeks (139.838.7 IU/ml), and were higher statistically than the values tested in the same weeks of abnormal pregnancies. In abnormal pregnancies serum CA-125 concentations were relatively lower than those of normal pregnancies. But these differences were not statistically significant except the values tested in amenorhea 6weeks. So serum levels of CA-125 may not be proved useful in monitoring of early pregnancies outcome.
Abortion, Missed ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, First* ; Pregnancy* ; Prospective Studies