• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.3
• /
• pp.149-155
• /
• 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 $D_3$.

• Biomolecules & Therapeutics
• /
• v.11 no.2
• /
• pp.119-125
• /
• 2003

The present study was conducted to investigate the effects of bornyl acetate on arterial blood pressure and vascular contractile responses in the normotensive rats and to establish the mechanism of action. Both phenylephrine (an adrenergi$\alpha$-receptor agonist) and high potassium (a membrane-depolarizing agent) caused greatly contractile responses in the isolated aortic strips. These phenylephrine (10$^{-5}$ M)-induced contractile responses were depressed in the presence of high concentrations of bornyl acetate (10∼20 $\mu\textrm{g}$/ml), but not affected in low concentrations of bornyl acetate (2.5∼5$\mu\textrm{g}$/ml). High potassium (5.6 ${\times}$ 10$^{-2}$ M)-induced contractile responses were also greatly inhibited in the presence of bornyl acetate (2.5∼20 $\mu\textrm{g}$/ml) in a dose-dependent fashion. Bornyl acetate (1∼10 mg/kg) given into a femoral vein of the normotensive rat produced a dose-dependent depressor response, which is transient (data not shown). Interestingly, the infusion of a moderate dose of bornyl acetate (3mg/kg/30 min) made a significant reduction in pressor responses induced by intravenous norepinephrine. Collectively, these results obtained from the present study demonstrate that intravenous bornyl acetate causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of adrenergic $\alpha$$_1$-receptors. bornyl acetate also causes vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic $\alpha$$_1$-receptors, in addition to the unknown mechanism of direct vasorelaxation.

• Natural Product Sciences
• /
• v.10 no.5
• /
• pp.228-236
• /
• 2004

The aim of the present study was to examine whether green tea extract (CUMC6335) affects the blood pressure and the isolated aortic contractility of the rabbit in comparison with one of the most powerful active catechins, epigallocatechin gallate (EGCG). The phenylephrine $(1-10\;{\mu}M)-induced$ contractile responses were greatly inhibited in the presence of CUMC6335 (0.3-1.2 mg/ml). Also, high potassium (56 mM)-induced contractile responses were depressed in high concentration (0.6-1.2 mg/ml), but not affected in low concentration CUMC6335 (0.3 mg/ml). However, epigallocatechin gallate $(EGCG,\;4-12\;{\mu}g/ml)$ did not affect the contractile responses evoked by phenylephrine and high $K^+$. The infusion of CUMC6335 with a rate of 20 mg/kg/30 min made a significant reduction in pressor responses induced by intravenous norepinephrine. However, EGCG (1 mg/kg/30 min) did not affect them. Collectively, these results obtained from the present study suggest that intravenous CUMC6335 causes depressor action in the anesthetized rat at least partly through the blockade of adrenergic ${\alpha}_1-receptors$. CUMC6335 also causes the relaxation in the isolated aortic strips of the rabbit partly via the blockade of adrenergic ${\alpha}_1-receptors$, in addition to the unknown direct mechanism. It seems that there is no species difference in the vascular effect between the rat and the rabbit.

• Archives of Pharmacal Research
• /
• v.26 no.3
• /
• pp.214-223
• /
• 2003

The present study was conducted to investigate the effects of green tea extract (GTE) on arterial blood pressure and contractile responses of isolated aortic strips of the normotensive rats and to establish the mechanism of action. The phenylephrine ($10^{-6}~10^{-5}M$)-induced contractile responses were greatly inhibited in the presence of GTE (0.3~1.2 mg/mL) in a dose-dependent fashion. Also, high potassium ($3.5{\times}10^{-2}~5.6{\times}10^{-2}{\;}M$)-induced contractile responses were depressed in the presence of 0.6~1.2 mg/mL of GTE, but not affected in low concentration of GTE (0.3 mg/mL). However, epigallocatechin gallate (EGCG, $4~12{\;}{\mu}g/mL$) did not affect the contractile responses evoked by phenylephrine and high $K^+$. GTE (5~20 mg/kg) given into a femoral vein of the normotensive rat produced a dose-dependent depressor response, which is transient. Interestingly, the infusion of a moderate dose of GTE (10 mg/kg/30 min) made a significant reduction in pressor responses induced by intravenous norepinephrine. However, EGCG (1 mg/kg/30 min) did not affect them. Collectively, these results obtained from the present study demonstrate that intravenous GTE causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of adrenergic $\alpha_1$-receptors. GTE also causes the relaxation in the isolated aortic strips of the rat via the blockade of adrenergic $\alpha_1$-receptors, in addition to the unknown direct mechanism. It seems that there is a big difference in the vascular effect between GTE and EGCG.

• The Korean Journal of Pharmacology
• /
• v.2 no.1 s.2
• /
• pp.41-48
• /
• 1966

The author studied the adrenotropic receptors of the non-pregnant uteri of the rabbit and rat, using epinephrine (alpha and beta activator), phenoxybenzamine(alpha blocking agent) and nethalide (beta blockade), and obtained the following results: 1. The spontaneous motility of isolated non-pregnant uteri from rabbits were stimulated by epinephrine, whereas that of isolated non-pregnant rat uterus was inhibited by epinephrine. 2. Both alpha and beta adrenergic receptors were present in the uterine muscle of both animals. 3. In the non-pregnant rabbit uterus, alpha receptors were predominant, whereas in the non -pregnant rat uterus, beta receptors preponderated over alpha receptors.

• The Korean Journal of Pain
• /
• v.12 no.2
• /
• pp.177-182
• /
• 1999

Background: Clonidine, an ${\alpha}_2$ adrenergic agonist blocks nerve conduction. However, in our previous experiment we found that adrenaline neither blocks nerve conduction by itself nor augment nerve conduction blockade by lidocaine near clinical concentrations. Possible explanations are: 1) there may be antagonism between some of adrenergic receptors, 2) clonidine may block nerve conduction via non-adrenergic mechanism. The purpose of this study is to obtain dose-response curves of several different forms of adrenergic receptor agonist to see the relative potencies of each adrenergic receptors to block nerve conduction. Methods: Recordings of compound action potentials of A-fiber components (A-CAPs) were obtained from isolated sciatic nerves of adult male Sprague-Dawley rats. Nerve sheath of the sciatic nerve was removed and desheathed nerve bundle was mounted on a recording chamber. Single pulse stimuli (0.5 msec, supramaximal stimuli) were repeatedly applied (2Hz) to one end of the nerve and recordings of A-CAPs were made on the other end of the nerve. Dose-response curves of epinephrine, phenylephrine, isoproterenol, clonidine were obtained. Results: $ED_{50}$ of each adrenergic agonist was: $4.51\times10^{-2}$ M for epinephrine; phenylephrine, $7.74\times10^{-2}$ M; isoproterenol, $9.61\times10^{-2}$ M; clonidine, $1.57\times10^{-3}$ M. Conclusion: This study showed that only clonidine, ${\alpha}_2$ adrenergic agonist, showed some nerve blocking action while other adrenergic agonists showed similar poor degree of nerve blockade. This data suggest that non-effectiveness of epinephrine in blocking nerve conduction is not from the antagonism between adrenergic receptors.

• Natural Product Sciences
• /
• v.11 no.1
• /
• pp.33-40
• /
• 2005

The present study was undertaken to investigate the effects of ${\beta}-eudesmol$, one of various ingredients isolated and identified from the bark of Magnolia obovata Thunberg, on arterial blood pressure and vascular contractile responses in the normotensve rats and to establish its mechanism of action. ${\beta}-Eudesmol\;(30{\sim}300\;{\mu}g/kg)$ given into a femoral vein of the normotensive rat produced a dose-dependent depressor response. These ${\beta}-eudesmol-induced$ hypotensive responses were markedly inhibited in the presence of chlorisondamine (1.0 mg/kg, i.v.) or phentolamine (2.0 mg/kg, i.v.). Interestingly, the infusion of ${\beta}-eudesmol$ (1.0 mg/kg/30min) into a femoral vein made a significant reduction in pressor responses induced by intravenous norepinephrine. Furthermore, the phenylephrine $(10^{-5}\;M)-induced$ contractile responses were depressed in the presence of high concentrations of ${\beta}-eudesmol\;(10{\sim}40\;{\mu}g/ml)$, but not affected in low concentration of ${\beta}-eudesmol\;(2.5{\sim}5\;{\mu}g/ml)$. Also, high potassium $(5.6{\times}10^{-2}\;M)-induced$ contractile responses were greatly inhibited in the presence of ${\beta}-eudesmol\;(10{\sim}40\;{\mu}g/ml)$ in a dose-dependent fashion. Taken together, these results obtained from the present study demonstrate that intravenous ${\beta}-eudesmol$ causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of vascular adrenergic ${\alpha}_1-receptors$, in addition to the some unknown mechanism of direct vasorelaxation.

• International Journal of Oral Biology
• /
• v.36 no.4
• /
• pp.173-178
• /
• 2011

Tumor necrosis factor alpha ($TNF{\alpha}$) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that ${\beta}2$ adrenergic receptor (${\beta}2AR$) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether $TNF{\alpha}$ modulates ${\beta}AR$ expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by $TNF{\alpha}$. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of ${\beta}AR$, ${\beta}2$ and ${\beta}3AR$ were found in our analysis to be upregulated by $TNF{\alpha}$. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in $TNF{\alpha}$-primed C2C12 cells, indicating that $TNF{\alpha}$ enhances ${\beta}2AR$ signaling in osteoblasts. $TNF{\alpha}$ was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a ${\beta}2AR$ antagonist, attenuated this $TNF{\alpha}$ suppression of osteogenic differentiation. $TNF{\alpha}$ increased the expression of receptor activator of NF-${\kappa}B$ ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that $TNF{\alpha}$ increases ${\beta}2AR$ expression in osteoblasts and that a blockade of ${\beta}2AR$ attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by $TNF{\alpha}$. These findings imply that a crosstalk between $TNF{\alpha}$ and ${\beta}2AR$ signaling pathways might occur in osteoblasts to modulate their function.

• Biomolecules & Therapeutics
• /
• v.13 no.1
• /
• pp.48-58
• /
• 2005

The present study was conducted to investigate the effects of nicorandil on arterial blood pressure and vascular contractile responses in the normotensive anesthetized rats and to establish the mechanism of action. Nicorandil (30~300 ${\mu}g/kg$) given into a femoral vein of the normotensive anesthetized rat produced a dose-dependent depressor response. These nicorandil-induced hypotensive responses were not affected by pretreatment with atropine (3.0 mg/kg, i.v.) or propranolol (2.0 mg/kg, i.v.), while markedly inhibited in the presence of chlorisondamine (1.0 mg/kg, i.v.) or phentolamine (2.0 mg/kg, i.v.). Futhermore, after the pretreatment with 4-aminopyridine (1.0 mg/kg/30 min, i.v.) or glibenclamide (50.0 ${\mu}g/kg$/30min) into a femoral vein made a significant reproduction in pressor responses induced by intravenous norepinephrine. In he isolated rat aortic strips, both phenylephrine (10$^{-5}$ M)- and high potassium (5.6 ${\times}\;10^{-2}$ M)-inducedcontractile responses were dose-dependently depressed in the presence of nicorandil (25~100 ${\mu}M$). Collectively, these experimental results demonstrate that intravenous nicorandil causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of vascular adrenergic ${\alpha}_1$-receptors, in addition to the well-known mechanism of potassium channel opening-induced vasorelaxation.

• Natural Product Sciences
• /
• v.20 no.3
• /
• pp.216-225
• /
• 2014

The present study was designed to investigate whether ethylacetate (EtOAc) fraction extracted from Rubus coreanum affect the contractility of the isolated thoracic aortic strips and blood pressure of normotensive rats. The EtOAc fraction ($400{\mu}g/mL$) significantly depressed both phenylephrine (PE, $10{\mu}M$)- and high $K^+$ (56 mM)-induced contractile responses of the isolated thoracic aortic strips in a concentration-dependent fashion. In the simultaneous presence of L-NAME (an inhibitor of NO synthase, $300{\mu}M$) and EtOAc ($400{\mu}g/mL$), both PE- and high $K^+$-induced contractile responses were recovered to the corresponding control level in comparison with inhibition of EtOAc-treatment alone. Moreover, in the simultaneous presence of EtOAc after pretreatment with 0.4% CHAPS, both PE- and high $K^+$-induced contractile responses were recovered to the corresponding control level compared to the inhibitory response of EtOAc-treatment alone. Also, in anesthetized rats, EtOAc fraction (0.3~3.0 mg/kg) injected into a femoral vein dose-dependently produced depressor responses. This hypotensive action of EtOAc fraction was greatly inhibited after treatment with phentolamine (1 mg/kg), chlorisondamine (1 mg/kg), L-NAME (3 mg/kg/30 min) or sodium nitroprusside ($30{\mu}g/kg/30 min$). Intravenous infusion of EtOAc fraction (1.0~10.0 mg/kg/30 min) markedly inhibited norepinehrine-induced pressor responses. Taken together, these results demostrate that EtOAc causes vascular relaxation in the isolated rat thoracic aortic strips as well as hypotensive action in anesthetized rats. These vasorelaxation and hypotension of EtOAc seem to be mediated at least by the increased NO production through the activation of NO synthase of vascular endothelium, and the inhibitory adrenergic modulation.