• The Korean Journal of Physiology and Pharmacology
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• 제12권1호
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• pp.31-35
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• 2008

Lysophosphatidylcholine (LPC), a metabolite of membrane phospholipids by phospholipase $A_2$, has been considered responsible for the development of abnormal vascular reactivity during atherosclerosis. $Ca^{2+}$ influx was shown to be augmented in atherosclerotic artery which might be responsible for abnormal vascular reactivity. However, the mechanism underlying $Ca^{2+}$ influx change in atherosclerotic artery remains undetermined. The purpose of the present study was to examine the effects of LPC on L-type $Ca^{2+}$ current $(I_{Ca(L)})$ activity and to elucidate the mechanism of LPC-induced change of $I_{Ca(L)}$ in rabbit portal vein smooth muscle cells using whole cell patch clamp. Extracellular application of LPC increased $I_{Ca(L)}$ through whole test potentials, and this effect was readily reversed by washout. Steady state voltage dependency of activation or inactivation properties of $I_{Ca(L)}$ was not significantly changed by LPC. Staurosporine (100 nM) or chelerythrine $(3{\mu}M)$, which is a potent inhibitor of PKC, significantly decreased basal $I_{Ca(L)}$, and LPC-induced increase of $I_{Ca(L)}$ was significantly suppressed in the presence of PKC inhibitors. On the other hand, application of PMA, an activator of PKC, increased basal $I_{Ca(L)}$ significantly, and LPC-induced enhancement of $I_{Ca(L)}$ was abolished by pretreatment of the cells with PMA. These findings suggest that LPC increased $I_{Ca(L)}$ in vascular smooth muscle cells by a pathway that involves PKC, and that LPC-induced increase of $I_{Ca(L)}$ might be, at least in part, responsible for increased $Ca^{2+}$ influx in atherosclerotic artery.

• BMB Reports
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• 제41권3호
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• pp.223-229
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• 2008

Reactive oxygen species (ROS) are implicated in vascular homeostasis. This study investigated whether ${O_2}^{\cdot^-}$, the foundation molecule of all ROS, regulates vasomotor function. Hence, vascular reactivity was measured using rat thoracic aortas exposed to an ${O_2}^{\cdot^-}$ generator (pyrogallol) which dose-dependently regulated both $\alpha$-adrenergic agonist-mediated contractility to phenylephrine and endothelium-dependent relaxations to acetylcholine. Pyrogallol improved and attenuated responses to acetylcholine at its lower (10 nM - 1 ${\mu}M$) and higher (10 - 100 ${\mu}M$) concentrations, respectively while producing the inverse effects with phenylephrine. The endothelial inactivation by L-NAME abolished acetylcholine-induced vasodilatations but increased phenylephrine and KCl-induced vasoconstrictions regardless of the pyrogallol dose used. Relaxant responses to sodium nitroprusside, a nitric oxide donor, were not affected by pyrogallol. Other ROS i.e. peroxynitrite and $H_2O_2$ that may be produced during experiments did not alter vascular functions. These findings suggest that the nature of ${O_2}^{\cdot^-}$-evoked vascular function is determined by its local concentration and the presence of a functional endothelium.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.621-628
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• 2016

Hypertension can be caused by various factors while the predominant causes include increase in body fluid volume and resistance in the circulatory system that elevate the blood pressure. Consumption of probiotics has been proven to attenuate hypertension; however, the effect is much strain-dependent. In this study, a newly isolated Lactobacillus casei (Lb. casei ) strain C1 was investigated for its antihypertensive properties in spontaneously hypertensive rats (SHR). Lactic acid bacteria (LAB) suspension of 11 log colony-forming unit (CFU) was given to SHR (SHR+LAB, n=8), and phosphate buffer saline (PBS) was given as a control in SHR (SHR, n=8) and in Wistar rats as sham (WIS, n=8). The treatment was given via oral gavage for 8 weeks. The results showed that the weekly systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and aortic reactivity function were remarkably improved after 8 weeks of bacterial administration in SHR+LAB. These effects were mostly attributed by restoration of wall tension and tensile stress following the bacterial treatment. Although not statistically significant, the level of malondialdehye (MDA) in SHR+LAB serum was found declining. Increased levels of glutathione (GSH) and nitric oxide (NO) in SHR+LAB serum suggested that the bacterium exerted vascular protection through antioxidative functions and relatively high NO level that induced vasodilation. Collectively, Lb. casei strain C1 is a promising alternative for hypertension improvement.

• Journal of Korean Neurosurgical Society
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• 제57권1호
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• pp.1-5
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• 2015

Objective : Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. Methods : The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately $-500{\mu}m$ in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). Results : We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin $PGH_2$. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. Conclusion : Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.87-92
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• 2001

Carbon monoxide (CO) binds to soluble guanylate cyclase to lead its activation and elicits smooth muscle relaxation. The vascular tissues have a high capacity to produce CO, since heme oxygenase-2 (HO-2) is constitutively expressed in endothelial and smooth muscle cells, and HO-1 can be greatly up-regulated by oxidative stress. Moreover, the substrate of HO, heme, is readily available for catalysis in vascular tissue. Although the activation of heme oxygenase pathway under various stress conditions may provide a defence mechanism in compromised tissues, the specific role of HO-1-derived CO in the control of aortic contractility still remains to be elucidated. The present study was done to determine the effect of HO-1 induction on the aortic contractility. Thus, the effects of incubation of aortic tissue with S-nitroso-N-acetylpenicillamine (SNAP) for 1 hr on the aortic contractile response to phenylephrine were studied. The preincubation with SNAP resulted in depression of the vasoconstrictor response to phenylephrine. This effect was restored by HO inhibitor or methylene blue but not by NOS inhibitor. The attenuation of vascular reactivity by preincubation with SNAP was also revealed in endothelium-free rings. $AlF4^--evoked$ contraction in control did not differ from that in SNP-treated group. These results suggest that increased production of CO was responsible for the reduction of the contractile response to phenylephrine in aortic ring preincubated with SNAP and this effect of SNAP was independent on endothelium.

• Journal of Chest Surgery
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• 제43권4호
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• pp.345-355
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• 2010

산성화를 초래하는 Hypoxia 등 여러 가지 조건에서 변화하는 세포외 pH 변화는 궁극적으로 세포내 pH 변화를 유발하며 세포 내외 pH 변화는 혈관평활근 수축성 변화를 유발한다. 이러한 세포 내외 pH 변화에 의한 혈관 수축성 변화 기전을 규명하고자, pH 변화가 혈관수축인자들에 의한 혈관평활근 수축, 혈관평활근세포내 $Ca^{2+}$ 농도, 그리고 혈관평활근의 $Ca^{2+}$에 대한 민감도에 미치는 영향을 알아보고자 하였다. 대상 및 방법: 쥐에서 분리한 상장간막동맥과 그 분지에서 등장성 수축을 기록하였으며 배양한 상장간막동맥 세포에서 세포내 $Ca^{2+}$ 변화를 측정하였다. 세포외 pH는 정상인 7.4에서 6.4, 6.9 혹은 7.8로 변화시켰으며, 세포내 pH 변화는 propionic acid나 $NH_4$를 투여하거나 ${\beta}$-escin으로 세포막의 투과성을 증가시켜 세포외 용액의 pH 변화로 유발시켰다. 결과: 세포외 pH를 7.4에서 6.9, 6.4로 감소시키면 노에피네프린과 세로토닌에 의한 용량-반응 곡선이 우측 이동하였으며 최대 수축력의 50% 수축력을 유발하는 농도(half maximal effective concentration)가 증가하였고, pH를 7.8로 증가시키면 그 반대 현상이 일어났다. 노에피네프린은 배양한 혈관평활근세포에서 세포내 $Ca^{2+}$ 농도를 증가시켰으며, 이 세포내 $Ca^{2+}$ 증가는 세포외 pH 감소에 의하여 억제되었으며 세포외 pH 증가에 의하여 증가하였다. 노에피네프린에 의한 수축은 세포내 pH를 감소시키는 $NH_4$에 의하여 억제된 반면, 안정 장력은 $NH_4$과 propionic acid에 의하여 증가하였다. ${\beta}$-escin으로 세포막의 투과도를 증가시킨 후 세포외 용액의 $Ca^{2+}$ 농도를 증가시켜 수축을 유발시킨 후 세포외 용액의 pH를 변화시키면 pH 감소에 의하여 수축력이 감소하였으며 증가에 의하여 수축력이 증가하였다. 결론: 세포외 pH의 감소는 혈관평활근의 수축성을 감소시키는데 이는 세포외 pH 감소에 의한 혈관평활근의 혈관수축물질에 대한 반응성 감소, 혈관평활근 세포내 $Ca^{2+}$ 유입 억제 그리고 $Ca^{2+}$에 대한 혈관평활근의 민감성 감소에 의하여 일어난 것으로 추정할 수 있었다.

• 한국음향학회:학술대회논문집
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• 한국음향학회 1999년도 학술발표대회 논문집 제18권 1호
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• pp.263-268
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• 1999

Psychoacoustic characteristics of automobile hems influence subject's subjective evaluation and psychophysiological reactions on the sounds of car horns. However, differentiation of physiological responses to commercially availablenfluence subject's subjective evaluation and psychophysiological reactions on the s horns is a complicated task due to the small contrast in technical features of horns and the influence of habituation. Using 10 college students, comparative analysis of physiological reactivity was carried out in order to identify the effect of habituation on decrement of psychophysiological responsivity, assess the ability to differentiate subjectively most and least preferred/appropriate horns according to physiological manifestations. EEG and autonomic responses to 7 automobile horns were analyzed during 3 blocks of trials (each block was varied in order for presenting stimuli and acoustic parameters of horns). It was shown that electrodermal and cardiovascular responses had different reactivity patterns to repeated stimulation. Skin conductance variables (SCL, SCR) were habituated as a function of trial. Cardiac reactivity (HR, RSA) showed no signs of habituation. In contrast, sensitization was shown in the vascular component of response (pulse volume). The temporal EEG exhibited marked habituation of fast beta band power, while alpha-blocking effect did not habituate during the course of experiment. Differentiation of physiological responses of most and least preferred/appropriate horns was possible in this study. That is, some cardiovascular reactivity variables (HR, RSA, pulse volume, etc.) were differentiated between the least and the most preferred/appropriate horns during the experiment. However, EEG and electrodermal parameters showed significant differences only during first block of trials and were later affected by habituation.

• 감성과학
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• 제3권2호
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• pp.17-28
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• 2000

Psychoacoustic characteristics of automobile horns play significant role in resulting subjective evaluation and psychphysiological reactions. However, comparison and differentiation of physiological responses to commercially available horns is a complicated task due to the small contrast in technical features of horns and the influence of such processes as habituation on physiological outcome with the increased number of auditory stimulation trials. In a study on 10 college students, there was performed comparative analysis of reactivity of physiological responses mediated by central and autonomic nervous systems in order to identify the role of habituation on decrement of psychophysiological responsivity and assess the ability to differentiate subjectively most and least preferred, as well as most and least appropriate horns according to physiological manifestations. The EEG and autonomic responses to 7 automobile horns were analyzed during 3 blocks of trials, with varying order of stimuli and changed acoustic parameters of horns in each block. Thus, responses were analyzed for totally 21 trials of auditory stimulation. It was shown that electrodermal and cardiovascular responses have different reactivity patterns to repeated stimulation: skin conductance measures habituated, cardiac reactivity showed no signs of habituation, and the vascular response demonstrated sensitization. The temporal EEG exhibited marked habituation of fast beta band power, while alpha-blocking effect did not habituate during the course of experiment. Differentiation of physiological responses of most and least preferred and appropriate horns was possible in our study, however, some cardiovascular reactivity measures differentiated during the entire course of the experiment, while EEG and electrodermal parameters showed significant differences only during first block of trials, and were later affected by the habituation.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.91-97
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• 2017

Hyperglycemia is associated with an increased risk of cardiovascular diseases. It has been demonstrated that chronic exposure to high glucose impaired endothelial functions. However, specific effects of short-term exposure to high glucose on vascular reactivity are controversial. Moreover, the combined effects of other metabolic substrates such as free fatty acids (FFA) on vascular reactivity remain poorly understood. Here we investigate the effects of short-term exposure to high glucose with or without other metabolic substrates including FFAs termed "nutrition full" (NF) solution, on mesenteric (MA) and deep femoral arteries (DFA) of rats. Arterial ring segments were mounted in a double-wire myograph. Contraction in response to phenylephrine (PhE) was determined in control (5 mM) and high glucose (23 mM, HG) environments over a 30 min period. In both arteries, PhE-inducedvasocontraction was enhanced by pre-incubation of HG solution. A combined incubation with HG and palmitic acid ($100{\mu}M$) induced similar sensitization of PhE-contractions in both arteries. In contrast, high $K^+$-induced contractions were not affected by HG. Interestingly, pre-incubation with NF solution decreased PhE-induced contraction in MA but increased the contraction in DFA. In NF solution, the HG-induced facilitation of PhE-contraction was not observed in MA. Furthermore, the PhE-induced contraction of DFA was attenuated by HG in NF solution. Our results demonstrate that the sensitization of PhE-induced arterial contraction by HG is differentially affected by other metabolic substrates. The conversation of skeletal arterial contractility by HG in NF solution requires careful interpretation of the previous in vitro studies where only glucose is included in physiological salt solutions. Further studies are required to elucidate the mechanism underlying the inconsistent effect of NF solution on MA and DFA.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.403-409
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• 2019

Free fatty acid (FFA) intake regulates blood pressure and vascular reactivity but its direct effect on contractility of systemic arteries is not well understood. We investigated the effects of saturated fatty acid (SFA, palmitic acid), polyunsaturated fatty acid (PUFA, linoleic acid), and monounsaturated fatty acid (MUFA, oleic acid) on the contractility of isolated mesenteric (MA) and deep femoral arteries (DFA) of Sprague-Dawley rats. Isolated MA and DFA were mounted on a dual wire myograph and phenylephrine (PhE, $1-10{\mu}M$) concentration-dependent contraction was obtained with or without FFAs. Incubation with $100{\mu}M$ of palmitic acid significantly increased PhE-induced contraction in both arteries. In MA, treatment with $100{\mu}M$ of linoleic acid decreased $1{\mu}M$ PhE-induced contraction while increasing the response to higher PhE concentrations. In DFA, linoleic acid slightly decreased PhE-induced contraction while $200{\mu}M$ oleic acid significantly decreased it. In MA, oleic acid reduced contraction at low PhE concentration (1 and $2{\mu}M$) while increasing it at $10{\mu}M$ PhE. Perplexingly, depolarization by 40 mM KCl-induced contraction of MA was commonly enhanced by the three fatty acids. The 40 mM KCl-contraction of DFA was also augmented by linoleic and oleic acids while not affected by palmitic acid. SFA persistently increased alpha-adrenergic contraction of systemic arteries whereas PUFA and MUFA attenuated PhE-induced contraction of skeletal arteries. PUFA and MUFA concentration-dependent dual effects on MA suggest differential mechanisms depending on the types of arteries. Further studies are needed to elucidate underlying mechanisms of the various effects of FFA on systemic arteries.