• Korean Journal of Veterinary Research
• /
• v.43 no.3
• /
• pp.373-382
• /
• 2003

Magnesium ion ($Mg^{2+}$) is a vasodilator, but little is known about its mechanism of action on vascular system. In vitro, extracellular magnesium sulfate ($MgSO_4$) produced relaxation in phenylephrine (PE) or high KCl-precontracted isolated rat thorocic aorta with (+E) or without (-E) endothelium in a concentration-dependent manner. The $MgSO_4$-induced relaxations were not affected by removal of the endothelium. Pretreatment of +E or -E aortic rings with nitric oxide synthase (NOS) inhibitors ($20{\mu}M$ L-NNA, $100{\mu}M$ L-NAME, $1{\mu}M$ dexamethasone and $400{\mu}M$ aminoguanidine), cyclooxygenase inhibitor ($10{\mu}M$ indomethacin), guanylate cyclase inhibitors ($10{\mu}M$ ODQ and $30{\mu}M$ methylene blue) and $Ca^{2+}$ transport blocker ($10{\mu}M$ ryanodine) did not affect the relaxant effects of $MgSO_4$. $Ca^{2+}$ channel blockers ($0.3{\mu}M$ nifedipine and $0.5{\mu}M$ veropamil) completely decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. However, in $Ca^{2+}$-free medium, $MgSO_4$-induced vasorelaxation was potentiated and this response was inhibited by nifedipine. Protein kinase C (PKC) inhibitors ($1.0{\mu}M$ staurosporine, $0.5{\mu}M$ tamoxifen and $0.1{\mu}M$ H7) or PLC inhibitor ($100{\mu}M$ NCDC) markedly decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. In vivo, infusion of $MgSO_4$ elicited significant decreases in arterial blood pressure. After intravenous injection of nifedipine ($150{\mu}g/kg$) and NCDC (3 mg/kg), infusion of $MgSO_4$ inhibited the $MgSO_4$-lowered blood pressure markedly. However, after introvenous injection of saponin (15 mg/kg), L-NNA (3 mg/kg), L-NAME (5 mg/kg), indomethacin (2 mg/kg), methylene blue (15 mg/kg) and aminoguanidine (10 mg/kg) failed to inhibit it. These results suggest that endothelial NQ-cGMP or prostaglandin pathway is not involved in vasorelaxant or hypotensive action of $Mg^{2+}$ and that these effects are due to the inhibitory action of $Mg^{2+}$ on the $Ca^{2+}$ channel or PLC-PKC pathway, and are due to the competitive influx of $Mg^{2+}$ and $Ca^{2+}$ through the $Ca^{2+}$ channel.

• The Journal of Korean Medicine
• /
• v.31 no.6
• /
• pp.47-57
• /
• 2010

Objective: The present study investigated the effect of ethanol extract of Cynanchum wilfordii (ECW) on vascular relaxation and vascular inflammation in rat artery isolated from rats and anti-inflammatory activity in human aortic smooth muscle cells (HASMC). Methods: Vascular tone and guanosine 3',5'-cyclic monophosphate (cGMP) production were examined in rat artery isolated from Sprague Dawley rats, in the presence of ECW. HASMC were incubated with tumor necrosis factor-alpha (TNF-${\alpha}$) or Angiotensin II for 24 h. Matrix metalloproteinase (MMP)-2 and anti-oxidant activity of ECW was investigated by pretreatment with ECW in HASMC. Results: Cumulative treatment of ECW relaxed aortic smooth muscles of rats in a dose-dependent manner. ECW-induced vasorelaxation was significantly decreased by pretreatment of L-arginine methyl ester (L-NAME) or oxadiazolo-quinoxalinone (ODQ). Furthermore, ECW treatment of thoracic aorta significantly increased cGMP production. Incubation of ECW with ODQ or L-NAME markedly decreased ECW-induced cGMP production. ECW treatment dose-dependently suppressed TNF-${\alpha}$- or Angiotensin II-induced increase in matrix metalloproteinase-2 expression in HASMC. Also, ECW exhibited 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity in vitro and reduced TNF-${\alpha}$-induced increase in reactive oxygen species production in a dose-dependent manner. Conclusions: Taken together, the results suggest that ECW exerts vascular relaxation via NO/cGMP signaling pathway and decreases MMP-2 expression via anti-oxidant activity.

• Journal of Convergence for Information Technology
• /
• v.10 no.10
• /
• pp.143-149
• /
• 2020

This study tried to observe the ability to inhibit vasocontriction in phloretin - the primary ingredient of apple tree leaves and the Manchurian apricot - through ROCK(Rho-associdated, coiled-coil containing protein kinase) inactivation in rat aortae. A piece of artery that was separated from Sprague-Dawley male rats and retained or damaged the endothelium was suspended in myograph tank with two metal rings, the lower ring fixed to the bottom of the tank, and the upper ring connected to the isotonic force transducer. Interestingly, phloretin inhibited fluoride- or phorbol ester-provoked contraction implying that additional pathways dissimilar from endothelial nitric oxide synthesis such as ROCK or MEK (mitogen activated protein kinase kinase) inactivation might be involved in the vasorelaxation. Therefore, this study provides that phloretin participates in the reduction of ROCK or MEK activity in smooth muscle in addition to the endothelial-dependent action of the endotheliuim in complete blood vessels, and consequently inhibits actin-myosin interaction in smooth muscle. Furthermore, phloretin inhibited thromboxane A2-induced contraction suggesting the mechanism including inhibition of ROCK and MEK.

• The Korean Journal of Physiology and Pharmacology
• /
• v.4 no.6
• /
• pp.471-477
• /
• 2000

In the rabbit renal artery, acetylcholine $(ACh,\;1\;nM{\sim}10\;{\mu}M)$ induced endothelium-dependent relaxation of arterial rings precontracted with norepinephrine $(NE,\;1\;{\mu}M)$ in a dose-dependent manner. $N^G-nitro- L-arginine$ (L-NAME, 0.1 mM), an inhibitor of NO synthase, or ODQ $(1\;{\mu}M),$ a soluble guanylate cyclase inhibitor, partially inhibited the ACh-induced endothelium-dependent relaxation. The ACh-induced relaxation was abolished in the presence of 25 mM KCl and L-NAME. The cytochrome P450 inhibitors, 7- ethoxyresorufin $(7-ER,\;10\;{\mu}M),$ miconazole $(10\;{\mu}M),$ or 17-octadecynoic acid $(17-ODYA,\;10\;{\mu}M),$ failed to inhibit the ACh-induced relaxation in the presence of L-NAME. 11,12-epoxyeicosatrienoic acid $(11,12-EET,\;10\;{\mu}M)$ had no relaxant effect. The ACh-induced relaxation observed in the presence of L-NAME was significantly reduced by a combination of iberiotoxin $(0.3\;{\mu}M)$ and apamin $(1\;{\mu}M),$ and almost completely blocked by 4-aminopyridine (5 mM). The ACh-induced relaxation was antagonized by $P_{2Y}$ receptor antagonist, cibacron blue $(10\;and\;100\;{\mu}M),$ in a dose-dependent manner. Furthermore, 2-methylthio-ATP (2MeSATP), a potent $P_{2Y}$ agonist, induced the endothelium-dependent relaxation, and this relaxation was markedly reduced by either the combination of iberiotoxin and apamin or by cibacron blue. In conclusion, in renal arteries isolated from rabbit, ACh produced non-NO relaxation that is mediated by an EDHF. The results also suggest that ACh may activate the release of ATP from endothelial cells, which in turn activates $P_{2Y}$ receptor on the endothelial cells. Activation of endothelial $P_{2Y}$ receptors induces a release of EDHF resulting in a vasorelaxation via a mechanism that involves activation of both the voltage-gated $K^+$ channels and the $Ca^{2+}-activated\;K^+\;channels$. The results further suggest that EDHF does not appear to be a cytochrome P450 metabolite.

• Journal of Ginseng Research
• /
• v.29 no.1
• /
• pp.1-18
• /
• 2005

Ginseng Radix, the root of Panax ginseng C. A. Meyer has been used in Eastern Asia for 2000 years as a tonic and restorative, promoting health and longevity. Two varieties are commercially available: white ginseng(Ginseng Radix Alba) is produced by air-drying the root, while red ginseng(Ginseng Radix Rubra) is produced by steaming the root followed by drying. These two varieties of different processing have somewhat differences by heat processing between them. During the heat processing for preparing red ginseng, it has been found to exhibit inactivation of catabolic enzymes, thereby preventing deterioration of ginseng quality and the increased antioxidant-like substances which inhibit lipid peroxide formation, and also good gastro-intestinal absorption by gelatinization of starch. Moreover, studies of changes in ginsenosides composition due to different processing of ginseng roots have been undertaken. The results obtained showed that red ginseng differ from white ginseng due to the lack of acidic malonyl-ginsenosides. The heating procedure in red ginseng was proved to degrade the thermally unstable malonyl-ginsenoside into corresponding netural ginsenosides. Also the steaming process of red ginseng causes degradation or transformation of neutral ginsenosides. Ginsenosides $Rh_2,\;Rh_4,\;Rs_3,\;Rs_4\;and\;Rg_5$, found only in red ginseng, have been known to be hydrolyzed products derived from original saponin by heat processing, responsible for inhibitory effects on the growth of cancer cells through the induction of apoptosis. 20(S)-ginsenoside $Rg_3$ was also formed in red ginseng and was shown to exhibit vasorelaxation properties, antimetastatic activities, and anti-platelet aggregation activity. Recently, steamed red ginseng at high temperature was shown to provide enhance the yield of ginsenosides $Rg_3\;and\;Rg_5$ characteristic of red ginseng Additionally, one of non-saponin constituents, panaxytriol, was found to be structually transformed from polyacetylenic alcohol(panaxydol) showing cytotoxicity during the preparation of red ginseng and also maltol, antioxidant maillard product, from maltose and arginyl-fructosyl-glucose, amino acid derivative, from arginine and maltose. In regard to the in vitro and in vivo comparative biological activities, red ginseng was reported to show more potent activities on the antioxidant effect, anticarcinogenic effect and ameliorative effect on blood circulation than those of white ginseng. In oriental medicine, the ability of red ginseng to supplement the vacancy(허) was known to be relatively stronger than that of white ginseng, but very few are known on its comparative clinical studies. Further investigation on the preclinical and clinical experiments are needed to show the differences of indications and efficacies between red and white ginsengs on the basis of oriental medicines.

• The Korean Journal of Pharmacology
• /
• v.32 no.1
• /
• pp.39-49
• /
• 1996

In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

• The Korean Journal of Pharmacology
• /
• v.29 no.2
• /
• pp.213-223
• /
• 1993

To investigate the endothelium dependent vascular reactivity of the systemic arterial and the pulmonary arterial system in acute renal hypertensive rats of 2-kidney, 1-ligation type (RHRs), acetylcholine (ACh)-induced vasodilation and depressor effects were evaluated in isolated arteries and in vivo, respectively, in the presence and absence of functional endothelium. ACh $(10^{-5}\;M)$ relaxed the intact thoracic aortas from RHRs and normotensive rats (NRs), but the effect was significantly smaller for those from RHRs (34 and 86%, respectively, p<0.01). ACh-induced vasodilation was completely abolished after removal of endothelial cell or pretreatment with EDRF inhibitors, L-NAME and MB, indicative of its dependence on intact endothelial or EDRF function. ACh also induced vasorelaxation of the intact pulmonary arteries from RHRs and NRs; however, unlike the effects on the thorcic aorta, no significant difference in amplitude was noted between two groups. ACh $(0.1{\sim}10\;{\mu}g/kg,\;i.v.)$ reduced mean systemic arterial pressure in anesthetized RHRs and in NRs to the similar magnitude (% change: 39 and 46% at $10\;{\mu}g/kg$, respectively) and these hypotensive effects were significantly decreased after pretreatment with L-NAME (30 mg/kg, i.v.). Deprssor effects of ACh on mean pulmonary arterial pressure were similar in RHRs and NRs with and without pretreatment of L-NAME. However, in both NRs and RHRs, the depressor effects of ACh on mean pulmonary arterial pressure were significantly reduced compared with those for mean systemic arterial pressure, and the increment of mean pulmonary arterial pressure noted after L-NAME $(0.1{\mu}100\;mg/kg,\;i.v.)$ was significantly smaller than that for mean systemic arterial pressure. These results indicate that in RHRs the endothelial cell function was impaired, at least in part, in systemic arterial system, but not in pulmonary arterial system, and both ACh-evoked and basal release of EDRF was less in the pulmonary arterial system than in systemic arterial system of both NRs and RHRs.