• The Korean Journal of Pharmacology
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• v.5 no.1
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• pp.35-38
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• 1969

1.On isolated atrial preparation of frog, effects of sympathomimetic amines were investigated. 2. Isoproterenol, epinephrine, norepinephrine, and phenylephrine produced positive chronotropic and inotropic effects. The relative potencies for the effects of these agents were: isoproterenol > epinephrine> norepinephrine> phenylephrine. Methoxamine had no effects or depressed the atria. 3. Pronethalol antagonized the positive effects of these adrenergic agents competitively. 4. Regitine did not affect the effects of these agents. 5. These data indicate that the adrenergic agents activate the atrial tissue of the frog via stimulation of adrenergic beta-receptor.

• YAKHAK HOEJI
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• v.30 no.3
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• pp.157-162
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• 1986

$\alpha$-Adrenoceptor subtypes in the isolated rat aortic strips were examined by using agonists and antagonists which have varying selectivity for $\alpha_1$- and $\alpha_2$- adrenoceptors. Norepinephrine and phenylephrine produced a similar magnitude of maximum contractions. $pA_2$ values for prazosin and yohimbine were not significantly different using norepinephrine or phenylephrine as the agonist, suggesting a single population of alpha-adrenoceptor. Contractile responses produced by alpha-agonists were antagonized more effectively by prazosin (approximately 1000 fold) than by yohimbine.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.87.2-88
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• 2003

The present study was conducted to investigate the effects of pinacidil, a potassium channel opener, on arterial blood pressure, catecholamine release and vascular contractile responses in the normotensve rats and to establish the mechanism of action. Phenylephrine (an adrenergi $_1$-receptor agonist) and high potassium (a membrane- depolarizing agent) caused greatly contractile responses in the isolated aortic strips, respectively. These phenylephrine (10$\^$-5/ M)-induced contractile responses were dose-dependently depressed in the presence of pinacidil (25 ∼ 100 ${\mu}$M). (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.216-216
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• 1996

The purpose of the present study was to determine whether in vivo noradrenergic neural activity in the locus coeruleus is related to the development of hypertension. Two groups of animals were prepared, 1) young spontaneously hypertensive rats (SHR) and 2) age-matched normotensive wistar kyoto rats (WKY). At il weeks of age, the release of norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DOPEG) from locus coeruleus of young SHR and WKY as an index of neural activity were determined by in vivo microdialysis along with blood pressure (BP) at three conditions : 1) normal; 2) elevated BP by systemic injection of phenylephrine and 3) alpha-1 adrenoceptor stimulated by perfusion of phenylephrine into the locus coeruleus through microdialysis probe. Basal releases of NE and DOPEG from the iocus coeruleus were 0.415+/-0.089pg/20min, 1.311+/-0.293 pg/20min in SHR and 0.204+/-0.078 pg/20min, 1.492+/-0.365 pg/20min in WKY respectively. Basal release of NE from the locus coeruleus of SHR was significantly greater than that of WKY. Phenylephrine systemic injection caused elevation of BP in both SHR and WKY in a dose related manner. Following phenyephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there were no significant changes in the releases of NE and DOPEG In young WKY. Alpha-1 adrenoceptor stimulation in the locus coeruleus by perfused phenylephrine through microdialysis probe caused pressor responses in both SHR and WKY, but the magnitude of pressor response in SHR was larger compared with that in WKY. The result from the present study suggests that noradrenergic neural activity in locus coeruleus may contribute as one of triggering factors for the expression of hypertension in young SHR.

• Journal of fish pathology
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• v.9 no.1
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• pp.41-51
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• 1996

The present study was undertaken to investigate the physiological characteristics of the adrenergic responses in the tilapia dorsal aorta. Epinephrine, norepinephrine, clonidine and methoxamine in the presence of propranolol($3{\times}10^{-6}$M), induced only endothelium-independent and concentration-dependent vasocontractions in tilapia dorsal aorta. The rank order of potency of adrenergic agonists inducing vasocontraction was epinephrine>norepinephrine>phenylephrine>clonidine>ethoxamine, Yohimbine produced a parallel shift of the concentration-vascontraction curves of epinephrine, norepinephrine, phenylephrine and clonidine to the right, while prazosin depressed the maximum responses of epinephrine and norepinephrine. Calcium-free physiological solution and verapamil markedly reduced epinephrine or norepinephrine-induced vasocontractions. These results suggest that a-adrenergic agonists produce only on endothelium-inedpenent casoconstrictions in tilapia dorsal aorta and these effect of a-adrenergic agonists, which might be associated with both calcium release from intracellular stores and calcium influx through voltage-dependent calcium channel.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.3
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• pp.149-155
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• 2003

The aim of the present study was to examine the effects of platycodin D and $D_3$, which are active components derived from the roots of Platycodon grandiflorum A. DC., on the contractile force of the i3olated rat aorta and blood pressure of the anesthetized rat, and also to elucidate its mechanism of action. Both phenylephrine (an adrenergic ${\alpha}1$-receptor agonist) and high potassium (a membranedepolarizing agent) caused great contractile responses in the isolated aortic strips. Platycodin D at high concentration $(24{\mu}g/ml)$ inhibited contractile responses induced by phenylephrine $(10^{-5}\;M)$ and high potassium $(5.6{\times}10^{-2}\;M)$, while low concentrations of platycodin D $(4{\sim}8{\mu}g/ml$) did not affect those responses. However, platycodin $D_3\;(8{\sim}32{\mu}g/ml)$ did not alter the contractile responses evoked by phenylephrine and high $K^+$. Interestingly, the infusion of platycodin $D_3$ (1.0 mg/kg/30 min) significantly reduced the pressor responses induced by intravenous norepinephrine. However, platycodin $D_3$ (1.0 mg/kg/30 min) did not affect them. Taken together, these results show that intravenously administered platycodin D depresses norepinephrine-induced pressor responses in the anesthetized rat, at least partly through the blockade of adrenergic ${\alpha}1$-receptors. Platycodin D also caused vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic ${\alpha}1$-receptors, in addition to an unknown direct mechanism. However, platycodin $D_3$ did not affect both norepinephrine-induced pressor responses and the isolated rat aortic contractile responses evoked by phenylephrine and high potassium. Based on these results, there seems to be much difference in the mode of action between platycodin D and platycodin $D_3$.

• Molecules and Cells
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• v.23 no.2
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• pp.175-181
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• 2007

The present study was undertaken to determine whether $SM22{\alpha}$ participates in the regulation of vascular smooth muscle contractility using $SM22{\alpha}$ knockout mice and, if so, to investigate the mechanisms involved. Aortic ring preparations were mounted and equilibrated in organ baths for 60 min before observing contractile responses to 50 mM KCl, and then exposed to contractile agents such as phenylephrine and phorbol ester. Measurement of isometric contractions using a computerized data acquisition system was combined with molecular or cellular experiments. Interestingly, the aortas from $SM22{\alpha}$-deficient mice ($SM22^{-/-LacZ}$) displayed an almost three-fold increase in the level of $SM22{\beta}$ protein compared to wild-type mice, but no change in the levels of caldesmon, actin, desmin or calponin. $Ca^{2+}$-independent contraction in response to phenylephrine or phorbol ester was significantly decreased in the $SM22{\alpha}$-deficient mice, whereas in the presence of $Ca^{2+}$ neither contraction nor subcellular translocation of myosin light chain kinase (MLCK) in response to phenylephrine or 50 mM KCl was significantly affected. A decrease in phosphorylation of extracellular signal regulated kinase (ERK) 1/2 was observed in the $SM22{\alpha}$-deficient mice and this may be related to the decreased vascular contractility. Taken together, this study provides evidence for a pivotal role of $SM22{\alpha}$ in the regulation of $Ca^{2+}$-independent vascular contractility.

• Journal of Veterinary Clinics
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• v.22 no.3
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• pp.220-227
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• 2005

Although ketamine has been used in the field of anesthetic medicine for its safety and favourable respiratory effects, the cardiovascular effects of ketamine is still controversial. To clarify the action and mechanism of ketamine upon cardiovascular system, arterial blood pressure, tension of aortic ring, left ventricular developed pressure and heart rate were measured in rats, Ketamine produced two types of effects on arterial blood pressure in anesthetized rats; monophasic effect (blood pressure lowering) and biphasic effect (initial transient blood pressure increasing following sustained lowering), The ketamine-induced lowering of aterial blood pressure showed a concentration-dependent manner, inhibited by the pretreament of $MgCl_2$ and potentiated by the pretreatment of $CaCl_2$. The ketamine-induced lowering of aterial blood pressure was suppressed by the pretreatment of nifedipine, verapamil or lidocaine. In phenylephrine-precontracted endothelium intact (+E) aortic rings, ketamine sometimes caused a small enhancement of contraction ($112.5{\pm}3.6{\%}$). However, in many experiments, ketamine produced a concentration-dependent relaxation in +E aortic rings precontracted with either phenylephrine or KCl. Ketamine-induced relaxation was significantly greater in KCl-precontracted strips than phenylephrine-precontracted strips. In phenylephrine-precontracted +E aortic rings, the ketamine-induced vasorelaxation was not suppressed by endothelium removal or by the pretreatment of a nitric oxide synthase inhibitors, L-$N^G$-nitro-arginine and a guanylate cyclase inhibitors, methylene blue, suggesting that the ketamine-induced vasorelaxation is not dependent on the endothelial function. In addition, ketamine elicited an increase in left ventricular developed pressure in perfused hearts accompanied by decrease in heart rate. These results suggest that ketamine could evoke a hypotension due to vasorelaxation and decrease in heart rate in rats. The inhibitory effect of cardiovascular system might be associated with modulation of $Ca^{2+}$ homeostasis.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.477-486
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• 2011

The purpose of the present study was to investigate whether polyphenol-rich fraction extracted from fruit wine of Rubus coreanum M (PCRC) can affect the contractility of the thoacic aortic strips isolated from spontaneously hypertensive rats (SHRs), and to clarify its mechanism of action. PCRC (200-800 ${\mu}g/mL$) concentration-depenedently blocked phenylephrine (10 ${\mu}M$)-induced contractile responses of the isolated aortic strips of SHRs. PCRC (400 ${\mu}g/mL$), added in to bath medium, also depressed the contractile active tension evoked by both phenylephrine (3 and 10 ${\mu}M$) and high potassium (25 and 56 mM). In the simultaneous presence of PCRC (400 ${\mu}g/mL$) and L-NAME (a selective inhibitor of NO synthase, 300 ${\mu}M$), the contractile responses evoked by phenylephrine and high $K^+$ were recovered to considerable level of the corresponding control contractility compared with those effects of PCRC-treatment alone. However, in the simultaneous presence of indomethacin (10 ${\mu}M$, a selective cyclooxygenase inhibitor) and PCRC (400 ${\mu}g/mL$), they were not affected. In the endothelium-denuded aortic strips by CHAPS-treatment, PCRC did not affect the contractile responses induced by phenylephrine or high potassium. Interestingly, PCRC (1.0, 3.0 and 10.0 mg/kg/30 min, i.v., respectively) dose-dependently suppressed norepiphrine-induced vasopressor responses in anesthetized SHRs. Collectively, we concluded that PCRC causes vasorelaxation in the thoracic aortic strips with intact endothelium of SHRs at least partly by the increased NO production through the activation of NO synthase of vascular endothelium, but not through the activation of cyclooxygenase. These results suggest that PCRC might be helpful to prevent or alleviate cardiovascular diseases, including hypertension.

• Journal of Ginseng Research
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• v.26 no.4
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• pp.178-186
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• 2002

The present study was attempted to investigate the effects of total ginseng saponin (G75), panaxadiol-type (PDS) and panaxatriol-type saponin (PTS) on contractile responses of vasoconstrictors in aortic smooth muscle stripes of normotensive (NR) and spontaneous hypertensive rats (SHR). Phenylephrine (an adrenergic $\alpha$$\_$1/-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in both NR and AHR aorta, respectively. Phenylephrine- and high potassium-induced contractile responses were greater in NA than those in SHR aortic smooth muscle stripes. In NR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and PTS (300 $\mu$g/ml), respectively whereas phenylephrine (10$\^$-6/ M)-induced contractile responses were markedly inhibited. In SHR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and moderate doses of PTS (150-300 $\mu$g/ml), respectively but greatly blocked by high concentration of PTS (600 $\mu$g/ml). Phenylephrine (10$\^$-6/ M)-induced contractile responses were inhibited in a dose dependent fashion (150-600 $\mu$g/ml) by the pretreatment with PTS while not altered in the presence of GTS (300 $\mu$g/ml) and PDS (300 $\mu$g/ml), respectively. Taken together, these experimental results suggest that ginseng saponins cause vascular relaxation through blockade of adrenergic $\alpha$$\_$1/-receptors and some unknown mechanisms, and that there is some difference in sensitivity of vascular smooth muscle between NR and SHR in responses to ginseng saponins. It seems that panaxatriol type of some ginseng saponins has the greatest potency in vascular relaxation.