interaction of volatile anesthetics with β-adrenoceptor stimulations on l-type ca2+ current of...

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Y-1. Interaction of volatile anesthetics with β-adrenoceptor stimulations on L-type Ca 2+ current of rabbit ventricular myocytes Liu Fan 1 , S. Sonoda 1 , M. Watanabe 2 , T. Kugimiya 1 , E. Inada 1 , T. Okada 2 . 1 Department of Anesthesiology, Juntendo University School of Medicine, Tokyo, Japan. 2 Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan Background: Volatile anesthetics suppress myocardial contractility and Ca 2+ current of cardiomyocytes. The suppres- sive effect of volatile anesthetics on Ca 2+ current is diminished in the presence of β-adrenoceptor stimulation. However, the interactions of volatile anesthetics with β-adrenoceptor- mediated signal transduction have not been entirely defined. The objective of the present study was to investigate the effects of sevoflurane (Sevo) and halothane (Halo) on β-adrenoceptor- mediated increase in L-type Ca 2+ current (I Ca,L ). Methods: I Ca,L was measured with whole-cell configuration of patch clamp technique in the enzymatically isolated rabbit ventricular myocytes. The effects of 1 minimum alveolar concentration Sevo (1.7%) and Halo (0.74%) on the isoproter- enol- (ISO, 30 nM) and forskolin- (FSK, 1 μM) induced increase in I Ca,L were examined. Results: Sevo and Halo significantly inhibited I Ca,L by 21.2 ± 1.7% and 35.0 ± 1.8%, respectively. In the control groups, ISO and FSK increased I Ca,L to 153 ± 7.0% and 240.3 ± 12.8%, respectively. ISO and FSK increased I Ca,L by 237.2 ± 25.4% and 328.5± 36.3% in the presence of Sevo, respectively. In the presence of Halo, ISO and FSK increased I Ca,L by 247.6 ± 16.3% and 242.8 ± 32.8%, respectively. Conclution: These results suggest that Sevo and Halo have suppressive effect on I Ca,L and they enhance the effect of β- adrenoceptor stimulation. However, the modulation site of Sevo may be different from that of Halo, because Sevo enhanced the effect of forskolin, which activate adenylate cyclase directly, but Halo did not. This study demonstrates that volatile anesthetics- induced modulation of β-adrenergic stimulation is through several pathways. Keywords: L-type Ca 2+ current; β-Adrenoceptor; Volatile anesthetics doi:10.1016/j.yjmcc.2007.07.011 Y-2. High-intensity voluntary exercise attenuates cardiac sympathetic activity in SPORTS (Spontaneously-Running-Tokushima-Shikoku) rats Masaki Morishima 1 , Yutaka Nakaya 2 , Katsushige Ono 1 . 1 Department of Cardiovascular Science, Oita University, Yufu, Japan. 2 Department of Nutrition and Metabolism, Tokushima University, Tokushima, Japan Background: We have previously generated a unique Wistar rat strain that displays an increased level of wheel running; we named it SPORTS (Spontaneously-Running-T okushima-Shi- koku). SPORTS rats run voluntarily in a running wheel appro- ximately ten times longer than control Wistar rats. Wheel running by rodent may correspond to voluntary exercise in human. Volun- tary exercise modifies cardiovascular and metabolic conditions that are dependent on exercise intensity and duration. However, the actual effects caused by different exercise/training intensities on cardiac vagal and sympathetic nerve activities that control cardiac chronotropism and inotropism are poorly understood. Objectives: The purpose of the present investigation was to study the effects of various intensities in voluntary exercise on sympathetic and vagal controls of heart at sedentary and during wheel-running exercise by use of SPORTS rats. Methods: Male SPORTS and normal Wistar (control) rats aged 34 weeks were housed in cages without an exercise wheel. At 15 weeks of age, each rat was moved to a new cage with or without an exercise wheel, and sorted into four groups: (1) SPORTS rat with an exercise wheel (running), (2) SPORTS rat without an exercise wheel (sedentary), (3) control rat with an exercise wheel (running), and (4) control rat without an exercise wheel (sedentary). Telemetric ECG signals were obtained for 30 min every 6 h at a sample rate of 1 kHz from an ECG radio- transmitter placed in a dorsal subcutaneous pouch of each rats. Autonomic nervous activity was evaluated by power spectral analysis of RR intervals. Results: Heart rate was significantly increased in sedentary SPORTS rats compared to those in control rats (control; 317 ± 6, SPORTS; 380±6 bpm). SPORTS rats show a significant reduction in resting heart rate by high-intensity running. The low-frequency/high-frequency (LF/HF) ratio, which reflects cardiac sympathetic nerve activity, was significantly decreased in SPORTS rats by voluntary running (sedentary; 6.0 ±1.0, running; 2.7 ± 1.2). However, a decrease of sympathetic nerve activity was not observed in control rats (sedentary; 4.9 ± 0.7, running; 8.6 ± 1.4) with approximately 1/10 wheel-running activity. By wheel running, the high-frequency (HF) power, as a parameter of vagal tone activity, was augmented in control rats, and was markedly depressed in SPORTS rats. Conclusion: High- but not low-intensity voluntary running decreases mean heart rate during resting period (sedentary) with a depression of sympathetic nerve activity. These results suggest that high-intensity voluntary exercise attenuates sympathetic nerve activity not only during exercise but also during resting period as a lasting effects. Keywords: SPORTS rat; Voluntary exercise; Sympathetic nerve activity doi:10.1016/j.yjmcc.2007.07.012 Y-3. Diacylglycerol kinase-ε prevents cardiac hypertrophy induced by phenylephrine infusion and aortic banding: A new specific regulator of Gαq signaling cascade Takeshi Niizeki, Yasuchika Takeishi, Tatsuro Kitahara, Yo Koyama, Toshiki Sasaki, Satoshi Suzuki, Isao Kubota. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan 437 ABSTRACTS / Journal of Molecular and Cellular Cardiology 44 (2008) 435450

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Y-1. Interaction of volatile anesthetics withβ-adrenoceptor stimulations on L-type Ca2+ current ofrabbit ventricular myocytesLiu Fan1, S. Sonoda1, M. Watanabe2, T. Kugimiya1, E. Inada1,T. Okada2. 1Department of Anesthesiology, Juntendo UniversitySchool of Medicine, Tokyo, Japan. 2Department of Physiology,Juntendo University School of Medicine, Tokyo, Japan

Background: Volatile anesthetics suppress myocardialcontractility and Ca2+ current of cardiomyocytes. The suppres-sive effect of volatile anesthetics on Ca2+ current is diminishedin the presence of β-adrenoceptor stimulation. However, theinteractions of volatile anesthetics with β-adrenoceptor-mediated signal transduction have not been entirely defined.The objective of the present study was to investigate the effectsof sevoflurane (Sevo) and halothane (Halo) on β-adrenoceptor-mediated increase in L-type Ca2+ current (ICa,L).

Methods: ICa,L was measured with whole-cell configurationof patch clamp technique in the enzymatically isolated rabbitventricular myocytes. The effects of 1 minimum alveolarconcentration Sevo (1.7%) and Halo (0.74%) on the isoproter-enol- (ISO, 30 nM) and forskolin- (FSK, 1 μM) inducedincrease in ICa,L were examined.

Results: Sevo and Halo significantly inhibited ICa,L by21.2±1.7% and 35.0± 1.8%, respectively. In the control groups,ISO and FSK increased ICa,L to 153±7.0% and 240.3±12.8%,respectively. ISO and FSK increased ICa,L by 237.2±25.4% and328.5± 36.3% in the presence of Sevo, respectively. In thepresence of Halo, ISO and FSK increased ICa,L by 247.6±16.3% and 242.8±32.8%, respectively.

Conclution: These results suggest that Sevo and Halo havesuppressive effect on ICa,L and they enhance the effect of β-adrenoceptor stimulation. However, the modulation site of Sevomay be different from that of Halo, because Sevo enhanced theeffect of forskolin, which activate adenylate cyclase directly, butHalo did not. This study demonstrates that volatile anesthetics-induced modulation of β-adrenergic stimulation is throughseveral pathways.

Keywords: L-type Ca2+ current; β-Adrenoceptor; Volatileanesthetics

doi:10.1016/j.yjmcc.2007.07.011

Y-2. High-intensity voluntary exercise attenuates cardiacsympathetic activity in SPORTS(Spontaneously-Running-Tokushima-Shikoku) ratsMasaki Morishima1, Yutaka Nakaya2, Katsushige Ono1.1Department of Cardiovascular Science, Oita University, Yufu,Japan. 2Department of Nutrition and Metabolism, TokushimaUniversity, Tokushima, Japan

Background:We have previously generated a unique Wistarrat strain that displays an increased level of wheel running; wenamed it SPORTS (Spontaneously-Running-Tokushima-Shi-koku). SPORTS rats run voluntarily in a running wheel appro-

ximately ten times longer than control Wistar rats. Wheel runningby rodent may correspond to voluntary exercise in human. Volun-tary exercise modifies cardiovascular and metabolic conditionsthat are dependent on exercise intensity and duration. However,the actual effects caused by different exercise/training intensitieson cardiac vagal and sympathetic nerve activities that controlcardiac chronotropism and inotropism are poorly understood.

Objectives: The purpose of the present investigation was tostudy the effects of various intensities in voluntary exercise onsympathetic and vagal controls of heart at sedentary and duringwheel-running exercise by use of SPORTS rats.

Methods: Male SPORTS and normal Wistar (control) ratsaged 3–4 weeks were housed in cages without an exercisewheel. At 15 weeks of age, each rat was moved to a new cagewith or without an exercise wheel, and sorted into four groups:(1) SPORTS rat with an exercise wheel (running), (2) SPORTSrat without an exercise wheel (sedentary), (3) control rat with anexercise wheel (running), and (4) control rat without an exercisewheel (sedentary). Telemetric ECG signals were obtained for30 min every 6 h at a sample rate of 1 kHz from an ECG radio-transmitter placed in a dorsal subcutaneous pouch of each rats.Autonomic nervous activity was evaluated by power spectralanalysis of RR intervals.

Results: Heart rate was significantly increased in sedentarySPORTS rats compared to those in control rats (control; 317± 6,SPORTS; 380±6 bpm). SPORTS rats show a significantreduction in resting heart rate by high-intensity running. Thelow-frequency/high-frequency (LF/HF) ratio, which reflectscardiac sympathetic nerve activity, was significantly decreasedin SPORTS rats by voluntary running (sedentary; 6.0±1.0,running; 2.7±1.2). However, a decrease of sympathetic nerveactivity was not observed in control rats (sedentary; 4.9±0.7,running; 8.6±1.4) with approximately 1/10 wheel-runningactivity. By wheel running, the high-frequency (HF) power, as aparameter of vagal tone activity, was augmented in control rats,and was markedly depressed in SPORTS rats.

Conclusion: High- but not low-intensity voluntary runningdecreases mean heart rate during resting period (sedentary) witha depression of sympathetic nerve activity. These results suggestthat high-intensity voluntary exercise attenuates sympatheticnerve activity not only during exercise but also during restingperiod as a lasting effects.

Keywords: SPORTS rat; Voluntary exercise; Sympathetic nerveactivity

doi:10.1016/j.yjmcc.2007.07.012

Y-3. Diacylglycerol kinase-ε prevents cardiac hypertrophyinduced by phenylephrine infusion and aortic banding:A new specific regulator of Gαq signaling cascadeTakeshi Niizeki, Yasuchika Takeishi, Tatsuro Kitahara, YoKoyama, Toshiki Sasaki, Satoshi Suzuki, Isao Kubota.Department of Cardiology, Pulmonology, and Nephrology,Yamagata University School of Medicine, Yamagata, Japan

437ABSTRACTS / Journal of Molecular and Cellular Cardiology 44 (2008) 435–450