BACKGROUND: Although hypoxic pulmonary vasoconstriction (HPC) and hypoxic coronary vasodilatation (HCD) have been recognized by many researchers, the precise mechanism remains unknown. As isolated arteries will constrict or relax in vitro in response to hypoxia, the oxygen sensor/transduction mechanism must reside in the arterial smooth muscle, the endothelium, or both. Unfortunately, much of the current evidence is conflicting, especially concerning to the dependency of HPC and HCD on the endothelium and the role of the K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPC and HCD on the endothelium and the role of the K+ channel on HPC and HCD. METHODS: HPC was investigated in isolated main pulmonary arteries precontracted with norepinephrine (NE). HCD was investigated in isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 +5% CO2, which was maintained for 15 - 25 min. RESULTS: 1)Hypoxia elicited a vasoconstriction in NE-precontracted pulmonary arteries with endothelium, but a vasodilatation in PGF 2 alpha-precontracted coronary arteries with and without endothelium. There was no difference between the amplitude of the HPC and HCD induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on subsequent response to hypoxia. 2)Inhibition of NO synthesis by the treatment with Nw-nitro-L-arginine reduced HPC in pulmonary arteries, but inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HPC and HCD, respectively. 3)Blockades of the TEA-sensitive K+ channel abolished HPC and HCD. 4)Apamin, a small conductance Ca2+/-activated K+ (KCa) channel blocker, and iberiotoxin, a large conductance KCa channel blocker, had no effect on the HCD. 5)Glibenclamide, an ATP-sensitive K+ (KATP) channel blocker, reduced HCD. 6)Cromakalim, an K(ATP) channel opener, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia and glibenclamide reduced both hypoxia- and cromakalim-induced vasodilations. 7)Verapamil, a Ca2+ entry blocker, caffeine, a Ca2+ emptying drug; and ryanodine, an inhibitor of Ca2+ release from SR, reduced HPC, respectively. CONCLUSION: HPC is dependent on the endothelium and is considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation while HCD is independent of the endothelium and is considered to be induced by activation of the K(ATP) channel.
Anoxia ; Arteries ; Caffeine ; Coronary Vessels ; Cromakalim ; Dinoprost ; Endothelium ; Glyburide ; Indomethacin ; Muscle, Smooth ; Norepinephrine ; Oxygen ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins F ; Pulmonary Artery ; Relaxation ; Ryanodine ; Vasoconstriction* ; Vasodilation*

It has been reported that kanamycin, a useful agent in the treatment of gram-negative and other infectious disease, has a negative inotropic action in isolated cardiac muscle preparation and also it decreases the amplitude of high K+ -induced action potential of guinea pig atrium. These findings imply that kanamycin has a property of Ca2+ antagonist. In this study, the effects of kanamycin on cardiac Ca2+ current were investigated in isolated rabbit ventricular cells by using a whole cell clamp nethod.The results are summarized as follows ; 1) Kanamycin caused a depression fo cardiac Ca2+ current in a dose dependent manner and its effect was observed in a whole memberane potential renge. 2) The decreasing effect of kanamycin on Ca2+ current was inhibited by high Ca(2+)-Tyrode solution and such inhibition was also observed in high Sr2+-Tyrode solution, but in the case of Cd2+, well known inorganic Ca2+ antagonist, the current through Ca2+ channel was greatly decreased when the perfuaste was changed from high Ca(2+)-Tyrode to high Sr(2+)-Tyrode solution. 3) In the presense of kanamycin, the decreasing pattern of Ca2+current by repetitve depolarization was not specific as in the case of verapamil. 4) Neomycin decreased Ca2+ current similar to kanamycin.From the above result, it may be concluded that kanamycin has competitive antagonistin effect on cardiac Ca2+ current.
Action Potentials ; Animals ; Calcium* ; Communicable Diseases ; Depression ; Guinea Pigs ; Kanamycin* ; Muscle Cells* ; Myocardium ; Neomycin ; Verapamil

BACKGROUND: No-reflow is a specific type of vascular damage occuring when removal of coronary occlusion dose not lead to restoration of coronary flow. There are three major explanations for the no-reflow phenomenon such as endothelial cell edema, microvascular plugging by platelets or thrombi and coronary occlusion by ischemic contracture of the myocardium. But detailed mechanisms of no-reflow phenomenon are not known. The objects of this study are to elucidate the possibility whether elevation of cytosolic Ca2+ concentration during ischemic cardioplegic period is mechanism of no-reflow phenomenon or not. METHODS: Changes in cytosolic Ca2+ concentration were measured under varying experimental condition. Free [Ca2+] in the cytosole [Ca2+]i of single rabbit coronary artery cells was measured with fluorescent Ca2+ indicator, Fura-2. RESULTS: Resting [Ca2+]i was 134.2+/-34 nM (n=43). When single cells were perfused with cardioplegic or ischemic cardioplegic solution, [Ca2+]i was significantly increased and degree of [Ca2+]i elevation was further augmented by ischemic cardioplegic solution. Pretreatment of sarcoplasmic reticulum emptying agent (20mM caffeine) had no effect on cardioplegia-induced [Ca2+]i change, but application of Ca2+ channel blocker (5x10-7M nifedipine) or an antagonist of Na+/Ca2+ exchange (5mM Ni2+ ) partially (nifedipine) or completely (nickel) inhibited the [Ca2+]i elevation. Pretreament of caffeine had no effect on ischemic cardioplegia-induced [Ca2+]i change, but application of nifedipine or nickel partially inhibited the [Ca2+]i elevation. Magnitude of ischemic cardioplegia-induced [Ca2+]i elevation was dependent on the Ca2+ concentration of perfusate from 0 to 2.5mM. When Ni2+ was added to reperfusion solution, recovery of ischemic cardioplegia-induced [Ca2+]i elevation was very rapid compared with control. CONCLUSIONS: From the above results, it may be speculated that ischemic cardioplegia-induced [Ca2+]i elevation may act as one of the mechanism of no-reflow phenomenon in rabbit coronary artery.
Caffeine ; Cardioplegic Solutions ; Coronary Occlusion ; Coronary Vessels* ; Cytosol* ; Edema ; Endothelial Cells ; Fura-2 ; Ischemic Contracture ; Muscle, Smooth* ; Myocardium ; Myocytes, Smooth Muscle* ; Nickel ; Nifedipine ; No-Reflow Phenomenon ; Reperfusion ; Sarcoplasmic Reticulum

The present study was intended to examine the effect of sodium vanadate on contractility of vascular smooth muscle. Aortic ring preparations were made from the rabbit thoracic aorta and endothelial cells were removed from the ring. The contractility of the aortic ring was measured under various conditions. The results were summarized as follows; 1) Sodium vanadate induced contraction of vascular smooth muscle in a dose-dependent fashion. 2) The contractile effects were not blocked by treatments with adrenergic blocking agent(phentolamine) and indomethacin, indicating the direct action of the drug on vascular smooth muscle. 3) In the presence of ouabain, Na(+)-K(+)-ATPase inhibitor, sodium vanadate still increased the contractility of vascular smooth muscle. 4) Treatment with 4.4'-diisothiocyanostilbene-2.2'-disulfonic acid(DIDS) blocked completely the contractile effects of sodium vanadate. 5) In the presence of verapamil, lanthanum and ryanodine, the contractility of the vascular smooth muscle by sodium vanadate was decreased. From the above results. it was suggested that sodium vanadate acts directly on vascular smooth muscle and causes contraction. It was probably due to inhibition of Ca(++)-ATPase in plasma membrane as well as increasing the release of Ca(++) from sarcoplasmic reticulum and Ca(++) influx across the plasma membrane, but not inhibition of Na(+)-K(+)-ATPase.
Aorta, Thoracic ; Cell Membrane ; Endothelial Cells ; Indomethacin ; Lanthanum ; Muscle, Smooth, Vascular* ; Ouabain ; Ryanodine ; Sarcoplasmic Reticulum ; Sodium* ; Vanadates* ; Verapamil

Caffeine has been known to induce the contraction of rabbit aortic ring resulting from Ca2+ release from the intracellular stores. But in contrast, contraction of aortic ring induced by depolarizing agents or agonist was reported to be suppressed by caffeine. The present study was intended to examine the effect of caffeine on Ca2+ movement across the plasma membrane and actomyosin ATPase activity of vascular smooth muscle to elucidate the modes of action of caffeine on the vascular smooth muscle. Aortic ring preparation were made from the rabbit thoracic aorta and the endothelial cells were removed from the ring by gentle rubbing. The contractilty of the aortic ring was measured under varying conditions, and Ca2+ influx across the membranes of the aortic ring was measured with Ca2+ sensitive electrode with and without caffeine and the effect of caffeine on actomyosin ATPase activity were measured by modified Hartshrone's method. 45Ca wash out curves with and without caffeine were studied by Richard's method. The results were summarized as follows: 1) Caffeine inhibited the contractilty induced by norepinephrine. high K+, and histamine. but caffeine alone induced a transient contraction of vascular smooth muscle. The caffeine induced contraction was demonstrable even in the absence of external Ca2+. 2) Caffeine increased 45Ca efflux from vascular smooth muscle. 3) In the presence of propranolol, the inhibitory effect of caffeine on epinephrine induced contraction still persisted. 4) Caffeine decreased norepinephrine induced Ca2+ influx through the plasma membranes of aortic ring. 5) Caffeine decreased the actomyosin ATPase activity of vascular smooth muscle. From the above results, it is suggested that caffeine induces the contraction of vascular smooth muscle by release of Ca2+ from intracellular Ca2+ stone, but inhibits drug-induced contraction by decrease of Ca2+ influx across the plasma membranes and a decreased Ca2+ sensitivity of contractile protein in vascular smooth muscle.
Actomyosin* ; Aorta, Thoracic ; Caffeine* ; Cell Membrane ; Electrodes ; Endothelial Cells ; Epinephrine ; Histamine ; Membranes ; Muscle, Smooth, Vascular* ; Myosins* ; Norepinephrine ; Propranolol

No abstract available.
Calcium* ; Erythrocytes* ; Sodium* ; Spherocytes

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

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

PURPOSE: The aim of this study was to design and evaluate a scale for measuring the attitudes toward condom use in sexual relationships. METHOD: A questionnaire was administered to 631 college students using a convenience sampling method. The psychometric properties (reliability and validity) were evaluated. RESULT: As a result of the item analysis, 16 items were selected and the internal consistency alpha coefficient was .88. Results indicated that the condom attitude scale is composed of three factors: Interruption of sexual pleasure; Protection; and Image. The three factors accounted for 59.54% of the variance in the total scale. Also, condom attitude was statistically significant (t=7.389, p=.000) between consistent condom users and inconsistent users. CONCLUSION: The results demonstrate that condom attitudes are multidimensional, and the reliability and validity of the scale was supported.
Adult ; *Attitude ; *Condoms ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Questionnaires ; Students/*psychology

Vanadate is a trace element in animal tissues and has been known to inhibit NA(+)-K(+) ATPase in various tissues including skeletal and cardiac muscles and smooth muscles. Vanadate shows contractile actions on various types of smooth muscles. Prolonged dietary administration of vanadate has been shown to cause arterial hypertension, increased peripheral resistance, and a marked reduction of coronary, visceral and renal blood flow.In isolated vascular smooth muscle of aorta, application of vanadate caused contraction. These studies have been conducted the preparation of vascular smooth muscles from which endothelial cell were removed. It has been reported that endothelial cell releases relaxing factor(s) (endothelium-derived relaxing factor, EDRF) in response to acetylcholine and a number of other stimuli and also produces vasoconstrictor substances (endothelium-derived contracting factor, EDCF). The aim of this present experiment is to elucidate whether vascular response of isolated rabbit aorta induced by vanadate are endothelium dependent or not. The result obtained were summarized as follows ; 1) When endothelium was intact, vanadate induced vascular relaxation of aorta precontracted with norepinephrine. But K+ induced contraction was augmented by vanadate in the aorta with or without endothelium. Whereas relaxation produced by vanadate precontracted with angiotensin II was endothelium-independent. 2) Hemoglobin, methylene blue, hydroquinone, and verapamil inhibited vanadate-induced vascular relaxation. But indomethacin and quinacrine had no effect on vanadate induced vascular relaxation. From the above results, it is speculated the vanadate act on endothelium, modifies the synthesis or release of endothelium-dependent relaxing factor and thus changes the contractile responses to norepinephrine in rabbit aorta.
Acetylcholine ; Adenosine Triphosphatases ; Angiotensin II ; Animals ; Aorta ; Endothelial Cells ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Hypertension ; Indomethacin ; Methylene Blue ; Muscle, Smooth ; Muscle, Smooth, Vascular* ; Myocardium ; Norepinephrine ; Quinacrine ; Relaxation ; Vanadates* ; Vascular Resistance ; Verapamil