• The Korean Journal of Pharmacology
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• v.5 no.1
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• pp.65-72
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• 1969

After administration of tetrabenazine (TBZ) 40 mg/kg), the pressor and cardioaccelerator responses of rabbits (whole anesthetized and spinal) to norepinephrine and tyramine were studied. The maxmal potentiation of the pressor activity of norepinephrine developed about 10 hours after TBZ administration. At this time the preesor response to tyramine was not decreased. The cardioaccelerator responses to both amines were not significantly altered. The TBZ-induced supersensitivity to norepinephrine was not increased by additional intravenous reserpine, but it was further increased by giving desipramine. Carbachol, given 2 and 6 hours after TBZ administration, inhibited the development of supersensitivity to norepinephrine by TBZ. The TBZ-induced supersensitivity was discussed in relation to reserpine-induced supersensitivity.

• The Korean Journal of Pharmacology
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• v.13 no.2
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• pp.19-34
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• 1977

1) The relationship of arterial blood pressure and heart rate with raised intracranial pressure induced by the epidural balloon method was investigated in anesthetized rabbits and cats. 2) In both animals marked increase of the blood pressure was observed when the intracranial pressure became close to the blood pressure. 3) In both animals marked decrease in the blood pressure and transitory marked decrease in the heart rate were observed, when the level of the intracranial pressure exceeded that of the blood pressure. 4) In reserpinized animals raised intracranial pressure produced decrease in the blood pressure and heart rate. 5) During raised intracranial pressure, the 6-hydroxydopamine-treated (by intracerebral administration) animals showed increase of the blood pressure less than control animals. 6) The depressor response to raised intracranial pressure in the reserpinized animals was reversed to the marked pressor one by the administration of norepinephrine into the lateral ventricle. 7) These results suggest that the pressor response to raised intracranial pressure is due to the increase of norepinephrine release resulted from local stimulation of the central sympathetic neurons by the raised intracranial pressure.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.309-321
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• 1995

In the present study, the relationship between the somatosympathetic reflexes and arterial blood pressure responses to electrical stimulation of the peripheral nerve was investigated in cats anesthetized with ${\alpha}-chloralose$. Single sympathetic postganglionic fiber activities were recorded from the hindlimb muscle and skin nerves and also from the cervical and abdominal sympathetic chains. Effects of the morphine on responses of the sympathetic nerve and arterial blood pressure to activation of the peripheral $A{\delta}-$ and C-afferent nerves were analyzed. The following results were obtained. 1) Arterial blood pressure was depressed by peripheral AS-afferent stimulation (A-response) and was elevated during C-afferent activation (C-response). 2) Intravenously administered morphine enhanced the C-response while the A-response decreased insignificantly, Only the C-response was decreased by intrathecal morphine. 3) All the ten recorded cutaneous sympathetic fibers showed periodic discharge pattern similar to respiratory rhythm and five of them also showed cardiac-related rhythm. However, most of the muscular sympathetic fibers had cardiac-related rhythm and only four fibers showed respiratory rhythm. 4) Morphine decreased the sympathetic C-reflex elicited by the peripheral C-afferent activation and the abdominal sympathetic A-reflex was also decreased by morphine. From the above results, it was concluded that supraspinal mechanisms were involved in the enhanced arterial pressor response to peripheral C-afferent activation by intravenous morphine.

• Archives of Pharmacal Research
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• v.17 no.3
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• pp.150-153
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• 1994

Ethanolic extract of Daucus carota (DC) at the dose of 10-100 mg/kg caused a dose-dependent fall in systolic and diastolic arterial blood pressure in nomotensive anesthetized rats. These effects were not blocked by atropine (1 mg/kg) and pretratment with DC did not alter the pressor response to norepinephrine indicating that cardiovascular effects of DC are independent of cholinergic or adrenergic recptors involvement. In spontaneously beating guinea-pig paired atria, DC induced a concentration-dependent (03-5 mg/ml) decrease in force and rate of atrial contractions. In rabbit thoracic aorta, DC caused inhibition of $K^+$-induced contractions at similar concentrations. These results suggest that the extract may exhibit $Ca^{2+}$ channel blocking-like direct relaxant action on cardiac and smooth muscle preperations and this action may be responsible for its hypotensive effect observed in the in vivo studies.

• Journal of Life Science
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• v.20 no.7
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• pp.969-976
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• 2010

In vivo studies of KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) were performed in pithed rats, conscious angiotensin II (AII) challenged normotensive rats, renal hypertensive rats (RHRs) and furosemide-treated beagle dogs. KR-31125 induced a non-parallel right shift in the dose-pressor response curve to AII ($ID_{50}$: 0.095 mg/kg) with a dose-dependent reduction in the maximum responses in pithed rats. Compared to losartan, this antagonistic effect was about 18 times more potent, presenting competitive antagonism. Other agonists such as norepinephrine and vasopressin did not alter the responses induced by KR-31125. Orally administered KR-31125 had no agonistic effect and dose-dependently inhibited the pressor response to AII with a slightly weaker potency ($ID_{50}$: 0.25 and 0.47 mg/kg, respectively) in the AII-challenged normotensive rat model, but with a more rapid onset of action than losartan (time to $E_{max}$: 30 min for KR-31125 and 6 hr for losartan). KR-31125 produced a dose-dependent antihypertensive effect with a higher potency than losartan in RHRs, and these effects were confirmed in furosemide-treated dogs where they presented a dose-dependent and long-lasting (>8 hr) antihypertensive effect with a rapid onset of action (time to $E_{max}$: 2-4 hr), as well as a 20-fold greater potency than losartan. These results suggest that KR-31125 is a potent, orally active $AT_1$ receptor antagonist that can be applied to the development of new diagnostic and research tools as an added exploratory potential of $AT_1$ receptor antagonist.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.105-116
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• 1996

Rendering the brain ischemic would evoke the cerebral ischemic reflex which is characterized by an arterial pressor response, apnea and bradycardia. Since the rostral ventrolateral medulla (RVLM) is known to play a key role in the maintenance of normal cardiopulmonary activity, during the cerebral ischemic reflex some cardiac related cells should be excited and respiration related cells inhibited. In this context, the responses of RVLM neurons to systemie and focal hypoxia were analyzed in the present study. Twenty-five adult cats of either sex were anesthetized with ${\alpha}-chloralose$ and the single neuronal activities were identified from RVLM area. For the induction of focal hypoxia in the recording site, sodium cyanide was applied iontophoretically and for systemic hypoxia the animal was ventilated with nitrogen gas for a twenty-second period. Cellular activities were analyzed in terms of their discharge pattern and responses to the hypoxia by using post-stimulus time and single-pass time histograms. Of eighteen cardiac related cells recorded from the RVLM area, twelve cells were excited by iontophoresed sodium cyanide and of twenty-five respiration related cells, fourteen cells were excited by iontophoresed sodium cyanide. Remaining cells were either inhibited or unaffected. Eight of fifteen cells tested with iontophoresed sodium lactate were excited and remaining seven cells were inhibited. Systemic hypoxia induced by nitrogen gas inhalation elevated the arterial blood pressure, but excited, inhibited or unaffected the single neuronal activities. Some cells showed initial excitation followed by inhibition during the systemic hypoxia. Bilateral vagotomy resulted in a decrease of arterial pressor response to the systemic hypoxia, and a slight decrease in the rhythmicity related to cardiac and/or respiratory rhythms. The single neuronal responses to either systemic or focal hypoxia were not affected qualitatively by vagotomy. From the above results, it was concluded that the majority of the cardiac- and respiration- related neurons in the rostral ventrolateral medulla be excited by hypoxia, not through the mediation of peripheral chemoreceptors, and along with the remaining inhibited cells, all these cells be involved in the mediation of cerebral ischemic reflex.

• Korean Journal of Pharmacognosy
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• v.21 no.2
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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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• v.13 no.1
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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.

• YAKHAK HOEJI
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• v.37 no.1
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• pp.41-48
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• 1993

The effect of captopril on the lung angiotensin converting enzyme (ACE) was investigated after 3 weeks oral administration (120~160 mg/kg/day) through drinking water in SpragueDawley rats. On the $^{125}$I-351A, an ACE inhibitor, binding assay in the isolated perpused lungs, the number of ACE molecules at the intrapulmonary endothelial cell surface was significantly decreased (p<0.001), and recovered to the normal level 7 days after discontinuation of captopril treatment. Intrapulmonary conversion ratio of Al to All was also significantly decreased (p<0.05) in the isolated perpused lungs. Bolus intravenous injection of angiotensin I did not showed pressor response in the both of systemic and pulmonary blood pressure of the anesthetized rats. ACE activity of the lung homogenates was also significantly reduced. These data consistently indicate the decrease of functionally active ACE molecule at the pulmonary artery after chronic captopril treatment. However, serum ACE activity was increased three fold in captopril treated rats compared to the normal rats. So, these results suggest that the functionally active ACE molecule at the pulmonary artery was still inhibited, which is directly associated with the antihypertensive effects, even if the total angiotensn converting enzyme induction was resulted after chronic captopril treatment.

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