• The Korean Journal of Physiology and Pharmacology
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• 제6권4호
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• pp.225-233
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• 2002

Kanagawa hemolysin (KH), an exotoxin produced from Kanagawa phenomenon-positive Vibrio parahemolyticus, has been shown to possess various biological activities including hemolysis, enterotoxicity, cytotoxicity, and cardiotoxicity. The aim of this study was to investigate the effect of KH on the cardiovascular system and its mechanism, employing in vivo and in vitro experiments of the rat. Intracerebroventricular (icv) administration of 100 mHU KH produced a marked and continuous pressor effect (icv KH-pressor effect), and the icv pressor effect was not repeatable. However, intravenous (iv) injection of the same dose of KH induced a prominent depressor effect (iv KH-depressor effect). The icv KH-pressor effect was inhibited by acid-denaturation, while the iv KH-depressor effect was not. Simultaneous icv administration of the three agents (ouabain, diltiazem, or bumetanide: $10{\mu}g/kg$ each) significantly reduced the pressor effect. The icv KH-pressor effect was inhibited by treatment with iv phentolamine or chlorisondamine, but was not affected by iv candesartan. The iv KH-depressor effect was repeatable and was attenuated by treatment with iv NAME or methylene blue. In vitro experiments using isolated thoracic aorta, $10^{-6}$ M phenylephrine (PE) and 50 mM KCl produced a sustained contraction. In rings contracted with either agents, KH showed relaxant responses in a concentration- dependent fashion and the relaxation (KH-vasorelaxation) was not dependent on the existence of the endothelium. The KH-vasorelaxation in the endothelium-intact rings contracted by PE was abolished by methylene blue treatment. In summary, the present findings suggest that in the icv KH-pressor effect the cation leak-inducing action of KH is implicated, which leads to the increased central sympathetic tone, that the iv KH-depressor effect results from the vasorelaxation via NO-guanylate cyclase system, and that the KH-vasorelaxation is independent of the endothelium and the guanylate cyclase system is involved in it. In conclusion, the mechanism of KH producing the icv pressor effect may not be identical to that of KH producing the iv depressor effect.

• 약학회지
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• 제22권3호
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• pp.148-156
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• 1978

An influence of bethanidine (B) onpressor effects of norepinephrine (NE) and tyramine (TR) was investigated in the whole rabbits. B, in a dose 1.0, 3.0 and 5.0 mg/kg, i.v., potentiated significantly the pressor effects of NE and TR. Reserpine and desipramine did not increase the NE effect that had been potentiated by B.B also made little modification of NE effect that had been potentiated by reserpine and desipramine. B increased the NE effect that had been potentiated by tranycypromine and guanethidine. The NE pressor effect potentiated by B was decreased by tranylcypromine, but not influenced by guanethidine. The TR pressor effect potentiated by B was not altered by reserpine and guanethidine, but decreased by desipramine and tranylcypromine. B increased the TR pressor effect that had been potentiated by guanethidine. B, when given after administration of reserpine, tranylcypromine or desipramine, exerted little influence on the TR effect. The mechanism of potentiation of NE and TR pressor effects by B seems to be similar to guanethidine, and the potency of B on the influence of NE and TR effects seems to be greater than guanethidine.

• 약학회지
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• 제36권4호
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• pp.379-389
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• 1992

In order to investigate the effect of nifedipine, $Ca^{+2}$ channel antagoninst, on the action of some drugs participating in blood pressure, this experiment was peformed in rabbits. Nifedipine decreased the pressor actions of norepinephrine, angiotensin and carotid artery clamping, but did not affect the pressor actions of tyramine and depressor actions of acetylcholine and pilocarpine. Nifedipine inhibited the potentiated pressor action of norepinephrine and angiotensin, but did not influence the potentiated pressor action of tyramine in rabbits pretreated with chlorisondamine, ganglionic blocking agent. Nifedipine weakened the potentiated pressor action of norepinephrine, did not affect the pressor action of angiotensin and the potentiated pressor action of tyramine in rabbits pretreated with debrisoquine, sympathetic neuronal blocking agent.

• The Korean Journal of Physiology
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• 제26권1호
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• pp.69-74
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• 1992

Central cardiovascular effects of bradykinin were examined in anesthetized normotensive (NTR) and 2-kidney, 1 clip Goldblatt hypertensive rats (GHR). Bradykinin ($0.5{\sim}10nmol$) was administered into the right lateral cerebral ventricle, while blood pressure and heart rate (HR) were continuously monitored. In both NTR and GHR, intracerebroventricular bradykinin produced a dose dependent increase in mean arterial pressure (MAP) without significant changes in HR. GHR were more sensitive in the pressor response than NTR. The pressor response to bradykinin was attenuated by treatment with hexamethonium (2.5mg/kg/min, IV) or phentolamine (2mg/kg, IV) in both NTR and GHR. Reserpine treatment (2mg/kg/day, intramuscularly,2 days) did not affect the central pressor effect of bradykinin in NTR but it attenuated the pressor effect in GHR. Pretreatment with indomethacin (10mg/kg, intraperitoneally) or saralasin ($20{\mu}g$/kg/min, IV) was without effects on the pressor response to bradykinin. These results indicate that the central pressor effect of bradykinin is, at least in part, due to excitation of the autonomic nervous activity. Mechanisms other than the enhanced sympathetic nervous activity ran. not be ruled out, However. It is also suggested that the sensitivity to bradykinin is increased in the GHR.

• 대한수의학회지
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• 제28권1호
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• pp.23-28
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• 1988

To examine the selectivity of diltiazem, used in the cardiovascular diseases, on alpha-1 and alpha-2 adrenoceptor-induced pressor responses, effect of diltiazem on alpha-adrenocepter agonist-induced pressor responses were investigated in urethane-anesthetized rabbits and spinal rabbits. The results are summarized as follows: 1. Intravenous diltiazem(10, 30, 100, 300, $1000{\mu}g/kg$) produced dose-dependent depressor response in rabbits. 2. Pressor responses to intravenous norepinephrine($10{\mu}g/kg$) and phenylephrine ($30{\mu}g/kg$) were inhibited by pretreatment with intravenous diltiazem in rabbits and no difference was noted between the degree of both inhibitions of the pressor response by diltiazem. 3. Presser responses to intravenous norepinephrine ($3{\mu}g/kg$), phenylephrine ($20{\mu}g/kg$) and clonidine ($300{\mu}g/kg$) were inhibited by pretreatment with intravenous diltiazem in spinal rabbits. No difference was noted between the inhibition of norepinephrine-induced pressor response and that of phenylephrine-induced pressor response by diltiazem. The inhibition of clonidine-induced pressor response by diltiazem was slightly prominent than that of norepinephrine- or phenylephrine-induced pressor response. These results suggest that diltiazem significantly inhibits both pressor responses mediated by alpha-1 and alpha-2 adrenoceptors.

• 대한약리학회지
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• 제3권1호
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• pp.15-18
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• 1967

Sympathetic ganglionic stimulants (DMPP, Wy-615, TMA and McN-A-343) produced pressor response in chickens anesthetized with phenobarbital sodium. In adrenalectomized chickens the pressor activity of DMPP, Wy -615 and TMA was less than in normal chickens but that of McN-A-343 was unchanged. Hexamethonium (20 mg/kg) and chlorisondamine (5 mg/kg), ganglionic blocking agents, reduced the pressor response to DMPP and Wy-615 but did not abolish the response. The pressor effect of McN-A-343 was not potentiated by the ganglionic flocking agents, but abolished by atropine.

• The Korean Journal of Physiology
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• 제25권2호
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• pp.201-209
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• 1991

The rostral ventrolateral medulla (RVLM) has been established recently as a sympathoexcitatory area. The present study was conducted to investigate whether the somatosympathetic pressor and/or depressor responses are mediated through RVLM in cats anesthetized with ${\alpha}-chloralose$. An occipital craniectomy was performed and ventrolateral medulla were stimulated either electrically or chemically to evoke changes in arterial blood pressure. And then the effect of lesions in the ventrolateral medulla on the changes in blood pressure elicited by the peripheral nerve stimulation was observed. Followings are the results obtained: 1) Pressor areas were found in the ventrolateral medulla, lateral reticular nucleus and rostral dorsal area. 2) Depressor areas were found mainly in the ventrolateral medulla rostral to the pressor areas. 3) Some areas showed biphasic responses: a depressor response to lower frequency and a pressor response to higher frequency stimulation. 4) After electrical lesion in pressor area in RVLM, the somatosympathetic pressor response was abolished or depressed markedly. The somatosympathetic depressor response, however, remained after the lesion. 5) Electrical lesion in the depressor area abolished somatosympathetic depressor response. From the above results it is concluded that somatosympathetic pressor response is mediated through RVLM, while somatosympathetic depressor response is not mediated through RVLM.

• 대한약리학회지
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• 제3권1호
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• pp.5-13
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• 1967

It has been reported by some investigators that pressor response of rabbits to sympathetic ganglionic stimulants was weak. In this paper it was attempted to investigate this problem more thorouglhy in urethane anesthetized rabbits. 1) In rabbits the approximate doses to elicit increase of about 20 mmHg of blood pressure were $100\;{\mu}g/kg$ with DMPP, $50\;{\mu}g/kg$ with Wy-615, $500\;{\mu}g/kg$ with TMA and with nicotine. The pressor activity of these substances was markedly augmented by treating animals with syrosingopine. 2) In adrenal-ligated rabbits pressor activity of the substances was markedly reduced. Treating the adrenal-ligated animals with syrosingopine augmented significantly the pressor activity of these substances except DMPP. Direct injection of DMPP and TMA into the adrenal produced mole pressor response than intravenous injection did. These date suggest that DMPP has greater effect on the adrenal medulla than the other substances. 3) In vagotomized and atropinized rabbits the pressor activity of these compounds was more marked than in normal rabbits. 4) The above facts indicate that the pressor activity of the ganglionic stimulants in rabbits was definitely low than in cats and dogs. The low responsiveness of the rabbits to these agents was discussed in the light of catecholamine releasing mechanisms, and extraganglionic actions of these substances.

• 대한약리학회지
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• 제26권2호
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• pp.101-111
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• 1990

흰쥐, 개, 고양이의 뇌내의 머스커린수용체에 작용함이 알려져 있는 physostigmine(PS)의 동맥혈압에 미치는 효과를 urethane마취토끼에서 조사하였다. 정맥내 (iv) PS $25{\sim}250{\mu}g/kg$은 혈압변동을 일으키지 않았다. 그러나 토끼를 chlorisondamine(CS), hexamethonium, 뇌실내 (icv) clonidine, icv xylazine, icv reserpine으로 처리후 또는 척수이단후에는 승압반응을 일으켰다. CS처리토끼의 iv PS승압반응은 prazosin또는 pirenzepine처리후에는 현저히 약화되었다. Iv PS는 CS처리나 척수이단토끼에서 일어나는 McN-A-343의 승압효과를 억제하였고 또 McN-A-343주입시에는 iv PS는 승압을 일으키지 않았다. DMPP의 승압효과는 iv PS의 영향을 받지 않았다. Icv PS $12{\sim}100{\mu}g/kg$은 승압반응을 일으켰고 이는 CS처리로 강화되었다. 이 승압효과는 완전치는 않으나 prazosin 또는 pirenzepine으로 억제되었다. Angiotensin II 길항약인 $(Sar^{1},\;Ala^{8})-angiotensin$ II와 prazosin또는 pirenzepine으로 토끼를 처리할때는 icv PS승압효과는 거의 볼 수 없었다. 그러나 이 angiotensin II 길항약은 prazosin, pirenzepine의 iv PS승압반응에 대한 억제효과는 항진시키지 않았다. Icv pirenzepine은 icv PS승압반응은 차단하였으나, iv PS승압효과에는 영향을 미치지 않았다. 본실험성적은 CS처리 및 척수이단토끼에서 볼 수 있는 iv PS승압은 교감신경절의 머스커린수용체의 흥분으로 일어나고, icv PS승압은 뇌내의 머스커린수용체의 흥분으로 교감신경계 및 angiotensin계의 활성도가 높아져서 일어남을 가리키고 있다. 또한 토끼에서는 교감신경절니코틴수용체차단, 교감신경절에 미치는 중추 교감신경의 지배력의 감소 또는 척수이단등으로 교감신경절 머스커린수응체의 감수성이 바꾸어지지 않은한 iv PS는 승압반응을 일으키지 못함을 시사하고 있다.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.96-103
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• 2001

These studies were investigated about influence of SKP 450, a $K^{+}$ channel opener, on the pressor actions induced by norepinephrine, angiotensin II and carotid artery occlusion in rats. Before these studies, effect of SKP 450 itself on blood pressure was examinated. SKP 450 produced the depressor action in proportionaly to dose of 0.3, 1.0 and 3.0 $\mu$g/kg given intravenously and this depressor action was weakened by pretreatment of glibenclamide, a $K^{+}$ channel blocker. The pressor action induced by norepinephrine, an alpha-adrenergic agonist, was blocked 1 hr after administation of SKP 450 in a dose of 3.0 $\mu\textrm{g}$/kg, i.v. and directly after in a dose of 6.0 $\mu\textrm{g}$/kg, i.v.. The pressor action induced by angiotensin II was blocked immediatly after treatment of SKP 450 in a dose of 3.0 $\mu\textrm{g}$/kg, i.v.. The pressor action caused by carotid artery occlusion was not affected by SKP 450 of 3.0 $\mu\textrm{g}$/kg, i.v., whereas markedly blocked by SKP 450 of 6.0 $\mu\textrm{g}$/㎦, i.v.. The potentiated-pressor actions of norepinephrine and angiotensin II by pretreatment of chlorisondamine, a autonomic ganglionic blocking agent, were also blocked by administration of SKP 450 in a dose of 6.0 $\mu\textrm{g}$/kg, i.v.. The weakened-pressor action of carotid artery occlusion by pretreatment of chlorisondamine was more weakened by SKP 450 6.0 $\mu\textrm{g}$/kg, i.v.. The results suggest that hyperpolarization formed through $K^{+}$ channel opening in cell membrane inhibits the pressor action induced norepinephrine ; angiotensin II ; and carotid artery occlusion.usion.