• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.629-638
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• 2006

This study was carried out to examine the relaxational response to the water extract of Sobokchuko-tang (SCT) in rat thoracic aorta. Segments of thoracic aorta obtained from rats immediately after delivery were mounted in organ baths superfused on a polygraph. It was found that the thoracic aorta segments responded to the SCT with dose-dependent vasorelaxation. At $10^{-7}M$ phenylephrine-induced contraction, the contractile response of thoracic aortic rings were inhibited by 99.2%. 75.3%. 42.4% and 35.8% after addition of the respective concentration (1O. 30. 100. $300{\mu}g$/ml) of SCT. This vasorelaxation of rat thoracic aorta was endothelium-dependent. The action mechanisms of vasorelaxation are thought to be concerned with the role of NO. cAMP and cyclooxygenase. but not with cGMP.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.385-395
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• 2017

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline ($10^{-6}M$ and especially $10^{-7}M$) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations ($10^{-4}M$ and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor $N^w$-nitro-L-arginine methyl ester (L-NAME; $10^{-4}M$) or NO scavanger $OHB_{12}$ ($10^{-3}M$), as well as non-specific inhibition of $K^+$-channels with tetraethylammonium (TEA; $10^{-3}M$), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin ($10^{-5}M$) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at $3{\times}10^{-7}$ and $10^{-6}M$, but not at the highest concentration ($10^{-4}M$). Neither the 5-$HT_{1D}$-receptor selective antagonist BRL 15572 ($10^{-6}M$) nor 5-$HT_7$ receptor selective antagonist SB 269970 ($10^{-6}M$) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and $K^+$-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-$HT_{2B}$ subtype.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.75-79
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• 1992

Higenamine, which is one of active component of Aconiti tuber, has been known to have positive inotropic effect through adrenergic beta-receptor. The effect of higenamine on norepinepharine or potassium induced contraction of pulmonary aorta in rabbit were studies. 1. The contraction of aortic strips induced by norepinephrine was suppressec by pre-or post-treatment of higenamine dose dependently and those effects of higenamine were prevented by propranolol. The $pA_2$ value of higenamine against propranolol calculated as 8.25. 2. The effect of higenamine was not affected by phentolamine. 3. Isoprotrenol has shown 10 times stronger vasodiatory effect on norepinephrine induced cntracture than that of higenamine but high concentration $(3.3{\times}10^{-6}\;M)$ of isoproterenol produce intrinsic activity. 4. Vasodilatory effect of higenamine or isoproterenol was not observed in potassium induced contacture of pulmonary aortic strips. These results strongly suggest that higenamine dilated the pulmonary vascular smooth muscle through stimulation of adrenergic beta-receptor.

• The Journal of Internal Korean Medicine
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• v.1 no.1
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• pp.25-34
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• 1976

The extract of commercial mistletoe caused transient contraction of mouse ileum in vitro at the level of $7{\times}10^{-4}g/ml$ and augmented significantly its peristalsis. When the ileum was pre-treated With $10^{-6}g/ml$ of adrenaline the administration of the extract at a level of $10^{-4}g/ml$ blocked the contraction. The increase inperistalsis and intention was also observed in rabbit ileum in vitro with the administration of the extract at a level of $10^{-1}g/ml$ but these phenomenon were inhibited by the adrenaline treatment at a level of $10^{-6}g/ml.$ When the extract was applied to spirally cut strips of thoracic aorta at the level of $10^{-3}g/ml$ the contractile action of adrenaline was significantly inhibited. When the extract was infused to auricular blood vessel of rabbit at the rate of $10^{-4}g/ml,\;10^{-3}g/ml,\;10^{-2}g/ml$ and $10^{-1}g/ml$ increases in number of drops by 70%, 77%, 93% and 100% were observed if the maximum number of drops caused by $10^{-1}g/ml$ is considered to be 100%. The duration of prolongation was proportionate to the increase in concentration of the extract. Hypotensive action of the extract and its duration were proportionately increased as the quantity of the extract increased. The increase in number and depth of respiration observed during the hypotensive status was brought to the normal when the tension became normal. In view of these observations it is concluded that the extract of commercial mistletoe has a contractile action of acetylcholine effect in the ileum of mouse and rabbit, loosens both aorta and smooth muscle and promotes peripheral circulation. As for the hypotensive action it is concluded that the action is brought about by the decrease in peripheral circulatory resistance due to the antagonism between acetylcholine and adrenaline.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.743-748
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• 2005

This study was performed for the investigation of vasodilatory efficacy and its underlying mechanisms of Jagumhuan(JGH), a herbal remedy. JGH produced completely endothelium-dependent relaxation and relaxed phenylephrine(PE)-precontracted aorta in a concentration dependent manner. The magnitude of relaxation was greater in PE induced contraction than that of KCl, suggesting involvement of $K^+$ channel in the relaxant effect. Both glibenclamide$(10^{-5}M)$, a $K_{ATP}$ channel inhibitor and indometacin, a cyclooxygenase inhibitor, completely prevented this relaxation. The relaxation effects of JGH, involve in part the release of nitric oxide from the endothelium as pretreatment with L-NAME, an NOS inhibitor, and methylene blue, a cGMP inhibitor, attenuated the responses by 62% and 58%, respectively. In addition, nitrite was produced by JGH in human aortic smooth muscle cells and human umbilical vein endothelial cells. The relaxant effect of JGH was also inhibited by 55.41% by tetraethylammonium(TEA; 5mM), a $K_{Ca}$ channel inhibitor. In the absence of extracellular $Ca^{2+}$, pre-incubation of the aortic rings with JGH significantly reduced the contraction by PE, suggesting that the relaxant action of the JGH includes inhibition of $Ca^{2+}$ release from intracellular stores. These results indicate that in rat thoracic aorta, JGH may induce vasodilation through ATP sensitive $K^+$ channel activation by prostacyclin production. However, the relaxant effect of JGH may also mediated in part by NO pathways and $Ca^{2+}$ activated $K^+$ channel.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.99-104
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• 2000

We investigated the action of NOS inhibitors on NOS in rats. Both of nitric oxide synthase inhibitors, $N^G$-monomethyl-L-arginine $(L-NMMA,\;3\;{\mu}M)$ or $N^G$-nitro-L-arginine methylester $(L-NAME,\;30\;{\mu}M),$ augmented phenylephrine $(PE,\;10^{-7}\;M)-induced$ contraction which was inhibited by acetylcholine (ACh) in rat thoracic aorta. This augmentation by L-NAME or L-NMMA was attenuated with the treatment of NO precursor, arginine. ACh, however, decreased the augmentation induced by L-NMMA, but not by L-NAME. Superoxide dismutase (SOD, 50 u/ml) potentiated an inhibitory effect of ACh on the PE $(10^{-7}\;M)-induced$ contraction. It has been known that platelet activating factor itself induces iNOS. Platelet activating factor $(PAF,\;10^{-7}\;M)$ inhibited PE $(10^{-7}\;M)-induced$ contraction. Pretreatment with L-NMMA (30 mM) or L-NAME (30 mM) significantly blocked the inhibitory action of PAF on PE-induced contraction. L-NMMA (100 mM) or L-NAME (100 mM) reduced nerve conduction velocity (NCV) relevant to nNOS in rat sciatic nerve. ACh attenuated the reduction of NCV by L-NMMA-, but not by L-NAME-induced reduction of NCV. These results suggest that L-NMMA and/or L-NAME have different action on three types of NOS in rats.

• The Korean Journal of Emergency Medical Services
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• v.23 no.3
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• pp.165-173
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• 2019

Purpose: Norepinephrine (NE) is a neurotransmitter of the sympathetic nervous system. It is used for treating hypotension on distributive shock, central nervous system injury, or sepsis. There are several reports that state that alcohol suppresses vasoconstriction by NE. Thus, our hypothesis is that the effect of NE is reduced in alcohol-drinking patients with distributive shock. We investigated whether alcohol suppresses NE-induced contraction and aimed at finding a solution to this problem. Methods: For this study, we used the aorta from male Sprague-Dawley rats (9-11 weeks) and an isometric contraction system. Results: Our results showed that alcohol suppresses NE contraction and does not affect epinephrine induced a contraction. Moreover, in the presence of alcohol, a 7:3 mixture of NE and epinephrine induced a contractile force similar to that induced by NE under normal conditions. Conclusion: We found that the vasoconstrictive force of NE decreased in the blood vessels in which alcohol was present, which was not because endothelial cells. The reduced contractile force was most similar to that induced by a 7:3 mixture of NE and epinephrine.

• BMB Reports
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• v.44 no.6
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• pp.415-420
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• 2011

Diabetes is a well-known independent risk factor for vascular disease. However, its underlying mechanism remains unclear. It has been reported that increased influx of the hexosamine biosynthesis pathway (HBP) induces O-GlcNAcylation of proteins, leading to insulin resistance. In this study, we determined whether or not O-GlcNAc modification of proteins could increase vessel contraction. Using an endothelium-denuded aortic ring, we observed that glucosamine induced OGlcNAcylation of proteins and augmented vessel contraction stimulated by U46619, a thromboxane $A_2$ agonist, via augmentation of the phosphorylation of MLC20$MLC_{20}$, MYPT1(Thr855), and CPI17, but not phenylephrine. Pretreatment with OGT inhibitor significantly ameliorated glucosamine-induced vessel constriction. Glucosamine treatment also increased RhoA activity, which was also attenuated by OGT inhibitor. In conclusion, glucosamine, a product of glucose influx via the HBP in a diabetic state, increases vascular contraction, at least in part, through activation of the RhoA/Rho kinase pathway, which may be due to O-GlcNAcylation.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.19-24
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• 2004

The vascular relaxant effect of amlodipine adipate, a new salt of amlodipine, was evaluate in isolated rat aorta, and compared with that of amlodipine besylate. Furthermore, antihypertensive effects were measured in hypertensive rat models, such as spontaneously hypertensive rats (SHR) and rena1 hypertensive rats (RHR). Amlodipine adipate concentration-dependently inhibited $Ca^{2+}$-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5 h;$IC_{50}$: 3.76 nM), having a pattern and a potency similar to those of amlodipine besylate ($IC_{50}$: 4.01 nM). In SHR and RHR, orally administered amlodipine adipate produced a dosedependent and long-lasting (>10-24 h) antihypertensive effect ($ED_{20}$: 2.48 and 1.57 mg/kg, respectively), with a pattern and a potency similar to those of amlodipine besylate ($ED_{20}$: 2.50 and 1.99 mg/kg in SHR and RHR, respectively). These results suggest that amlodipine adipate is a potent and long-lasting antihypertensive agent and that its antihypertensive effect is not significantly different to that of amlodipine besylate.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.485-493
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• 2005

We studied the effects of trazodone on arterial blood pressure in anesthesized guinea pigs, and on vascular responses in isolated thoracic aorta. Trazodone produced a concentration-dependent relaxation in phenylephrine-precontracted endothelium intact (+E) rings, but not in a KCl-precontracted aortic rings. These relaxant effects of trazodone on +E rings were significantly greater than those on denuded (-E) rings. The trazodone-induced relaxation was suppressed by glibenclamide and tetrabutylammonium, but not by N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), methylene blue (MB), nifedipine, indomethacin, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC) and clotrimazole. In vivo, infusion of trazodone elicited a significant decrease in arterial blood pressure. Trazodone-induced blood pressure lowering was markedly inhibited by intravenous pretreatment of prazosin but not by pretreatment of saponin, L-NNA, L-NAME, MB, nifedipine, glibenclamide, clotrimazole and NCDC. In addition, trazodone produced an increase in twitch force of isolated papillary muscle and left ventricular pressure of perfused heart. These findings suggest that the endothelium-independent vasorelaxant effect of trazodone may be explained by activation of $Ca^{2+}$-activated and ATP-sensitive $K^+$ channels, and the hypotensive effect of trazodone is not associated with cardiac contraction.