• 약학회지
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• 제31권2호
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• pp.82-91
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• 1987

The effect of neurotoxic compound 6-hydroxydopamine (6-OHDA) on the change in blood pressure and contractile response of Vas deference by centrally acting agents has been studied in normal and DOCA-salt induced hypertensive rats. The treatment of neonatal rats with 6-OHDA (2$\times$100mg, 250mg Kg$^{-1}$s.c) significantly inhibited the antihypertensive and relaxant effects of Vas deference of clonidine(100$\mu\textrm{g}$ Kg$^{-1}$iv.). The simultaneous administration of desipramine with clonidine into neonatal rats decreased the antihypertensive response of clonidine although treated did not affect the relaxative response of Vas deference. Furthermore, the antihypertensive and relaxant responses of clonidine were reduced by the neonatal rats with 6-OHDA regardless of the administration of desipramine. When neonatal rats were administered with 6-OHDA, the development of DOCA-salt hypertension was prevented. These results suggest that 6-OHDA, clonidine and desipramine hada significant effect on the development and the inhibition of central hypertension mediating the central adrenergic neuron due to their affinity to the central nervous system.

• Journal of Pharmaceutical Investigation
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• 제6권2호
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• pp.101-110
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• 1976

1. In the rabbit and the dog, the blood pressure response to water extract and methanol extract obtained from Atractylodes rhizoma alb'a was investigated. 2. Water extract and methanol extract, when administered into the rabbit and the dog by the route of vein, produced fall of the blood pressure. 3. The depressor response of the rabbit to water extract and methanol extract was not affected by $Avicel{\circledR}$, propranolol and atropine. 4. The depressor response by water extract and methanol extract in the rabbit was not affected by guanethidine, but water extract and methanol extract produced elevation of blood pressure in this rabbit. 5. Pretreatment of rabbit with chlorisendamine or phenoxybenzamine weakened the depressor response to water extract and methanol extract, and the both extracts produced secondary elevation of blood pressure in this rabbit. 6. The pressor response of the chlorisondamine-treated rabbit to water extract and methanol extract was not affected by atropine. 7. Water extract decreased the pressor action of tyramine and depressor action of pilocarpine and isoproterenol, but did not affect the blood pressure response of nor einephrine, angiotensin and dimethylpehnyl piperazinium iodide(DMPP).

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.299-305
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• 2008

Active cardiovascular anaphylactic response was induced in ovalbumin-sensitized, pithed Sprague-Dawley and Wistar rats. On intravenous administration of the antigen, ovalbumin, marked tachycardia and pressor responses were immediately elicited. Thereafter, a delayed long-lasting severe hypotensive response was observed. These anaphylactic cardiovascular responses were maximal 2-3 weeks after the sensitization, and the response was slightly diminished 6 weeks after sensitization. The immediate pressor response was blocked by a non-selective serotonin antagonist methysergide at a dose-dependent manner, but not by histamine receptor antagonists mepyramine (pyrilamine) or cimetidine. The delayed hypotension was reduced either by histamine $H_1$ receptor antagonist mepyramine or $H_2$ receptor antagonist cimetidine, both in a dose-dependent manner. The tachycardic response was not influenced by serotonin or histamine receptor antagonists examined in this study. Differently from the cardiovascular responses, there was no observable bronchial contraction in Sprague-Dawley rat trachea in contrast to Wistar rat where the trachea contracted to in vitro antigen challenge. The cardiovascular anaphylactic model seems to be useful for studying cardiovascular events that occur exclusively in peripheral heart-blood vessel systems. The involvement of two major anaphylactic mediators, serotonin and histamine, is partially demonstrated.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.370-373
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• 1998

Ten substituted phenacyl derivatives of 4-hydroxypiperidine were synthesized and studied for their effects on the mean arterial blood pressure (MABP) in normotensive anaesthetized rats and smooth muscles contractions of isolated rabbit jejunum. Two derivatives caused fall in blood pressure at the dose of 10-20 mg/kg and one rise in blood pressure at the dose of 20 mg/kg. Two compounds exhibited biphasic response (hypotensive followed by hypertensive) and one gave triphasic response at 10 mg/kg dose. Rest of four derivatives were found devoid of any effect on mean arterial blood pressure up to the dose of 30 mg/kg. All the derivatives except two caused relaxant effect on the spontaneous contraction of rabbit jejunum at the dose range of 0.1 -2 mg/kg.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.383-391
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• 1999

This study was carried out to determine whether the effects of an ${\alpha}_2-adrenoceptor$ agonist, clonidine, on mean arterial pressure (MAP) and heart rate (HR) are influenced by mild hypothermia. Experiments were performed in respiration-controlled and spontaneously breathing pentobarbital-anesthetized rats. Rectal temperature was maintained at $37.5{\pm}0.3^{circ}C$ for normothermic groups or at $35.2{\pm}0.3^{circ}C$ for mild hypothermic groups. Intravenous injection of clonidine (1 and 2 ${\mu}g/kg)$ produced depressor and bradycardic responses in spontaneously breathing rats under both normothermic and mild hypothermic condition: a decrease in MAP was not altered but bradycardic response was significantly augmented in the mild hypothermic group as compared with the normothermic group. Under the respiration-controlled condition, the hypotensive effect of clonidine $(2\;{\mu}g/kg)$ was reduced, whereas the bradycardic effect was increased in mild hypothermic rats as compared with normothermic rats. Both hypotensive and bradycardic effects of clondine $(2\;{\mu}g/kg)$ were blocked by pretreatment with an ${\alpha}_2-adrenoceptor$ antagonist, yohimbine (0.5 mg/kg), in both thermal conditions. Yohimbine (0.5 mg/kg, i.v.) alone produced signifcantly an increase in heart rate in the mild hypothermic group than in the normothermic group. Pretreatment with a muscarinic receptor antagonist, atropine methylnitrate (1 mg/kg, i.v.), attenuated the bradycardic effect of clonidine in the mild hypothermic group but not in the normothermic group. These results suggest that clonidine- induced bradycardia is amplified by mild hypothermia probably through an increased parasympathetic activity.

• Journal of Ginseng Research
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• 제23권2호
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• pp.81-87
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• 1999

신성고혈압백서모델인 one-kidney, one-clip Goldblatt 고혈압백서에서 혈압과 NO생성에 미치는 고려홍삼 사포닌과 비사포닌의 영향을 규명하고자, 무마취 무제한상태에서 혈압을 측정하고, 혈중 NO와 NO합성효노에 대한 활성 및 단백량을 실시한 결과이다. 고려홍삼 사포닌은 정상혈압백서 및 신성고혈압백서에서 모두 혈압을 강하시키는 효과가 현저하였는데 혈압강하는 초기 2-4분 동안 최대를 보였으며 혈압강하와 동시에 심박수의 증가 현상이 관찰되었다. 그러나 고려홍삼 비사포닌은 혈압강하효과와 심박수의 증가현상은 사포닌에 비하여 미미 하였다. 고려홍삼 사포닌에 의한 혈압강하 현상과 NO와의 상관관계를 규명하기 위하여 혈중 NO를 측정한 결과 홍삼사포닌은 혈중 NO를 상승시켰다. NO합성효소의 활성도를 측정하기 위하여 $[^{3}H]-L-arginine$의 $[^{3}H]-L-cioulline$으로의 변환률을 측정한 결과 고려홍삼 사포닌에 의하여 NO합성효소의 활성도는 증가하였다. 이상의 결과를 종합해 볼 때 고려홍삼은 혈압을 강하시키는 효과가 있으며, 이러한 혈압강하는 주로 사포닌 성분에 의한 것으로 생각된다. 이러한 고려홍삼 혈압강하 현상은 혈중의 NO량을 증가시키는 것에 기인하며 NO의 증가는 NO합성효소의 활성도의 증가에 기인하는것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.77-86
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• 2022

The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings precontracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018-185 ㎍/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 ㎍/kg. A concentrationdependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10^-6 M), the addition of PHAR-DBH-Me to the superfusion solution (10^-12-10^-5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB₁ receptor antagonist (AM 251) did not modify the response, while CB₂ receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10^-5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB₂ receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.

• 생약학회지
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• 제21권2호
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• pp.173-178
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• 1990

This study was attempted to examine the effect of Sopung-Tang(SPT) on the arterial blood pressure in rats and to elucidate its mechanism of action. SPT given into a femoral vein produced a dose-related vasopressor responses followed by vasodepressor responses. SPT-induced hypotension was significantly inhibited by pretreatment with atropine or propranolol while was not affected by chlorisondamine, Prazosin and cyproheptadine. SPT-evoked hypertensive activity was markedly blocked by pretreatment with prazosin but was not influenced by atropine, chlorisondamine, propranolol and cyproheptadine. Infusion of SPT(15.0 mg/kg/30min) did not affect norepinephrine-induced pressor responses. These experimental results suggest that SPT causes biphasically initial hypertensive activity followed by hypotensive activity, and that this hypertension may be due to the stimulation of peripheral adrenergic alpha-receptors and hypotension may be elicited through stimulation of peripheral cholinergic muscarinic receptors and adrenergic beta-receptors.

• Biomolecules & Therapeutics
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• 제13권1호
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• pp.48-58
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• 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
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• 제16권2호
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• pp.123-132
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• 2010

The aim of the present study was to investigate whether self-fermented pine extract for 2 years (SFPE2) and ethyl acetate (EtOAc) fraction from self-fermented pine needle extract may affect the contractility of the isolated aortic strips and blood pressure of normotensive rats. SFPE2 ($360-1440\;{\mu}g/mL$) significantly depressed both phenylephrine ($10\;{\mu}M$)- and high potassium (56 mM)-induced contractile responses of the isolated rat aortic strips in dose-dependent fashion. The EtOAc-fraction ($400\;{\mu}g/mL$) also inhibited both phenylephrine ($10\;{\mu}M$)- and high potassium (56 mM)-induced contractile responses. Also, in anesthetized normotensive rats, intravenous injection of the EtOAc fraction (1.0~10.0 mg/kg) dose-dependently elicited hypotensive responses. The EtOAc fractions (1.0 and 3.0 mg/kg/30 min) inhibited norepinehrine-induced pressor responses. Intravenous infusion of SFPE2 fraction (3.0 and 10.0 mg/kg/30 min) also inhibited norepinehrine-induced pressor responses in both anesthetized spontaneously hypertensive rats (SHRs) and normotensive rats. In conclusion, these results suggest that both SFPE2 and the EtOAc fraction cause vascular relaxation in the aortic strips isolated from normotensive rats and SHRs as well as vasodepressor responses. Based on these experimental data, it seems that SFPE2 or the EtOAc fraction possesses active antihypertensive components, which are available to prevent or treat hypertension in future.