• Journal of Chest Surgery
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• 제24권7호
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• pp.637-646
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• 1991

Effect of noradrenaline and endothelium on the high K+ or Ach-induced contraction were investigated in the pig myocardial coronary artery. The helical strip of isolated pig myocardial coronary artery was immersed in the Tris-buffered Tyrode`s solution equilibrated with 100% O2 at 37oC and its isometric tension was measured. High K+ and Ach-induced contraction were dose-dependent. By denuding the endothelium, dose-contraction curve of K+ was not shifted significantly to the left and upward, but that of Ach was shifted significantly to same direction 25 mM K+ - and Ach-induced contraction were relaxed by norepinephrine[NE]. NE-induced relaxation was blocked by the pretreatment of propranolol, which was known as b-adrenoceptor blocker. And, phenylephrine known as a-adrenoceptor agonist, and clonidine known as a-adrenoceptor agonist increased the 25mM K+ - induced contraction respectively. Denuding of endothelium did not show any significant effects on NE-induced relaxation and contraction increased by phenylephrine and clonidine. Tyramine increased 25mM K+ - induced contraction further. The contractile response by tyramine on the 25mM K+ - induced contraction was not blocked by the pretreatment of phentolamine, but was partially blocked by the pretreatment of atropine. From the above results, it is suggested that activation of a1-and a2-adrenoceptors induce the contraction, activation of b-adrenoceptors induce the relaxation, and NE-induced relaxation is mainly due to activation of b-adrenoceptors. Also it is suggested that denudation of endothelium did not influence NE-induced relaxation, but influence Ach-induced contraction in the pig myocardial coronary artery.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.99-108
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• 1989

The effects of prostaglandin $(PGF_{2{\alpha}})$ on the contractility of vascular smooth muscle were investigated in the helical strip of the rabbit aorta. The aortic strip was immersed in the phosphate-buffered Tyrode's solution which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$ and its isometric tension was measured. The contraction was induced by $(PGF_{2{\alpha}})$, norepinephrine (NE), or potassium (40 mM) in the nomal Tyrode's solution (1 mM, $Ca^{2+}$) or $Ca^{2+}-free$ Tyrode's solution. Effects of verapamil and phentolamine on the contraction were also observed. The aortic strip began to contract at the concentration of $5\;{\mu}g%$ and reached the maximal contraction at the concentration of $150\;{\mu}g%$ $(PGF_{2{\alpha}})$. The maximal contraction was corresponded respectively to $52.2{\pm}3.0%$ and $81.5{\pm}3.5%$ of maximal contraction by NE $(1{\times}10^{-5}M)$ and 40 mM $K^{+}$. And the maximal contractions by $(PGF_{2{\alpha}})$ or NE were induced at the concentration of about 1 mM $Ca^{2+}$. $(PGF_{2{\alpha}})$ induced the contraction of aortic strip even after induction of contraction by 40 mM $K^{+}$ and the contraction by $(PGF_{2{\alpha}})$ was not blocked by the ${\alpha}-receptor$ blocker, phentolamine. And the contraction by the $(PGF_{2{\alpha}})$ was inhibited partially by a verapamil at the concentration of $1{\times}10^{-5}M$ and the contraction began to increase at the concentration of $1{\times}10^{-4}M$ verapamil. Whereas the contraction by NE was completely blocked by verapamil. Though both the $(PGF_{2{\alpha}})$ and NE induced the contraction in the $Ca^{2+}-free$ Tyrode's solution, the peak tension was not maintained. But the rate of tension decline was lower in the contraction by $(PGF_{2{\alpha}})$ than in that by NE. The verapamil did not inhibit the contraction by $(PGF_{2{\alpha}})$ in the $Ca^{2+}-free$ Tyrode's solution and increased the contraction at the concentration of above $1{\times}10^{-4}M$. The NE-induced contraction in the $Ca^{2+}-free$ Tyrode's solution was inhibited completely by a verapamil. From the above results it is suggested that the contraction induced by $(PGF_{2{\alpha}})$ results from the promotion of the both $Ca^{2+}$ influx and the intracellular $Ca^{2+}$ release by different way from NE.

• The Korean Journal of Physiology
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• 제27권1호
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• pp.27-35
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• 1993

Effects of the endothelium on the contractile responses to norepinephrine (NE) were investigated in isolated helical strips of the proximal and distal coronaries artery of pigs. The helical strips were immersed in Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $35^{\circ}C$ and its isometric tension was measured. NE relaxed the strips precontracted with acetylcholine from both the proximal and distal coronary artery. NE-induced relaxation, which might be induced mainly by $\beta$-adrenoceptor function was dominant in the distal coronary arteries. NE-induced relaxation was converted to a contraction after $\beta$-adrenoceptor blockade with propranolol $(3{\times}10^{-6}M)$. ${\alpha}$-adrenoceptor-mediated contraction by NE was greater in the proximal coronary artery than the distal coronary artery. Quantitatively, ${\alpha}_1$-adrenoceptor mediated contraction by NE was greater than ${\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries. NE-induced relaxation was decreased by rubbing of endothelium in both arteries. ${\alpha}_1-and\;{\alpha}_2$-adrenoceptor mediated contraction by NE were potentiated by rubbing of endothelium in both arteries. Pretreatment with methylene blue, an inhibitor of soluble guanylate cyclase, increased ${\alpha}_1-\;and\;{\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries with endothelium. From the above results, we suggest that the effect of activation of $\alpha$-adrenoceptors by NE may be modulated by endothelium in the proximal and distal coronary arteries of pigs. This effect may be mediated via endothelium derived relaxing factor.

• 동의생리병리학회지
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• 제17권2호
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• pp.493-498
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• 2003

Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamchotang have been used in Oriental Medicine for many centuries as a treatment for various disease. The purpose of the present study is to determine the effect of Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamchotang on narepinephrine(NE) induced contraction of isolated rabbit femoral artery. Rabbits (2.0kg, female) were killed by CO₂ exposure and a segment (8-10mm) of the aortic ring from each rabbit was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 1.5g loading tension. The dose of NE which evoked 50% of maximal response (ED/sub 50/) was obtained from cumulative dose response curves for NE (10/sup -7/～10/sup -4/M). Contractions evoked by NE (ED/sub 50/) were inhibited significantly by Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamcho-tang. The mean percent inhibition of NE induced contraction was 83.9% (p<0.01) after 150㎕/㎖ Paeoniae Radix, 101.1 %(p<0.01) after 150 ㎕/㎖, Glycyrrhizae Radix and 107.3%(p<0.01) after 150㎕/㎖ Jakyakgamcho-tang, Indomethacin slightly but significantly attenuated the inhibitory effects of Paeoniae Radix. Following treatment with indomethacin, the mean percent inhibition caused by 150㎕/㎖ Paeoniae Radix fell to 16.4% in femoral artery induced by NE contraction. Propranolol, ODQ, and L-NNA did not significantly alter the inhibitory effect of Paeoniae Radix. ODQ slightly but significantly attenuated the inhibitory effects of Glycyrrhizae Radix. Following treatment with ODQ, the mean percent inhibition caused by 150㎕/㎖ Glycyrrhizae Radix fell to 13.0% in femoral artery induced by NE contraction. Propranolol, indomethacin and L-NNA did not significantly alter the inhibitory effect of Glycyrrhizae Radix. L-NNA slightly but significantly attenuated the inhibitory effects of Jakyakgamchotang. Following treatment with L-NNA, the mean percent inhibition caused by 150㎕/㎖ Jakyakgamchotang fell to 13.8% in femoral artery induced by NE contraction. Propranolol, ODQ and indomethacin did not significantly alter the inhibitory effect of Jakyakgamcho-tang. These results indicate that Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamcho-tang can relax NE induced contraction of the isolated rabbit femoral artery, and that this inhibition related to nitric oxide.

• 한국응급구조학회지
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• 제23권3호
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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.

• The Korean Journal of Physiology
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• 제23권2호
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• pp.351-361
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• 1989

The contraction of renal arterial strip by no.epineph.me (NE) or 40 mM $K^+$ were Significantly attenuated after histamine $(10^{-5}\;M)-induced$ contraction. The mechanisms of this phenomenon were investigated in the helical strips of isolated renal artery with the measurement of isometric tension. The arterial strip was immersed in the tris-buffered Tyrode's solution which was equilibrated with 100% $O_2\;at\;35^{\circ}C$. The contraction was induced by NE or 40 mM $K^+$ during the recovery from the histamine-induced contraction which lasted for 15 minutes. The contraction by NE was also attenuated in the $Ca^{2+}-free$ Tyrode's solution and the increase of contraction by addition of 2 mM $Ca^{2+}$ was attenuated as well. This attenuation phenomenon was not observed in the presence of low concentration $(3{\times}10^{-7}\;M)$ of histamine. This attenuation was not affected by destruction of endothelium, pretreatment with papaverine or propranolol. This attenuation was partially inhibited by pretreatment of ouabain or in low $K^+(0.5 mM)$ Tyrode's solution. But the attenuation in the $Ca^{2+}-free$ Tyrode's solution was not inhibited. Furthermore this attenuation was completely blocked by pretreatment of djphenhydramine $(H_1-receptor blocker)$ and potentiated by pretreatment of cimetidine $(H_2-receptor\;blocker)$. This attenuation Phenomenon was disappeared after recovery of 1 hour. From the above results, it is suggested that the attenuation phenomenon may be resulted partially from the activation of $Na^+-K^+$ exchange pump and partially from the depletion of intracellular $Ca^{2+}$ pool after the histamine-induced contraction mediated through $H_1-receptor$ function.

• 동의생리병리학회지
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• 제27권4호
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• pp.437-445
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• 2013

This study was investigated to evaluate the vasorelaxant effect of Rubus coreanus(RC) extract on contracted rabbit carotid artery and its mechanism. To study the effect of RC extract on contracted rabbit carotid arterial strips, arterial strips with intact or damaged endothelium were used for experiment using organ bath. The pre-contracted arterial strips with norepinephrine(NE) or potassium chloride(KCl) was treated with various concentrations of an extract of RC(0.01, 0.03, 0.1, 0.3 and 1.0 $mg/m{\ell}$). To determine the mechanisms of RC-induced vasorelaxant, RC extract was infused into contracted arterial rings which had been pretreated by indomethacin(IM), tetraethylammonium chloride(TEA), $N{\omega}$-nitro-L-arginine (L-NNA), methylene blue(MB). And calcium chloride(Ca) 1 mM was infused into precontracted arterial ring induced by NE or KCl after treatment of RC extract in $Ca^{2+}$-free krebs solution. Cytotoxic activity of RC extract on human umbilical vein endothelial cell(HUVEC) was measured by MTT assay, and nitric oxide(NO) prodution was measured by Griess reagent. RC extract revealed significant relaxation on NE-induced arterial contraction, but didn't relax on KCl-induced arterial contraction. RC extract also had an effective relaxation to the intact endothelium arterial ring, but not the damaged endothelium arterial ring. Treatment of IM, TEA, L-NNA, MB reduced the relaxation of RC extract. Pretreatment of RC extract inhibited the contraction by influx of extracellular $Ca^{2+}$ in contracted arterial ring induced by NE, but it didn't work the contraction by influx of extracellular $Ca^{2+}$ in contracted arterial ring induced by KCl in $Ca^{2+}$-free krebs solution. RC extract increased nitric oxide production on HUVEC. This study indicated that the relaxation effect of RC extract on contracted rabbit carotid artery is related with NO-cGMP pathway, EDHF, prostacyclin.

• The Korean Journal of Physiology
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• 제24권1호
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• pp.67-76
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• 1990

The contractile mechanisms of serotonin were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the normal or $Ca^{2+}$-free tris-buffered Tyrode's solution, which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$. The contraction by serotonin or norepinephrine (NE) began at $1{\times}10^{-7}\;M$ and reached the maximal contraction at $1{\times}10^{-5}\;M$. The maximal contraction by serotonin corresponded to $58.1{\pm}4.2%$ of maximal contraction by NE. Cyproheptadine, a serotonin receptor blocker, shifted the concentration-response curve to the right without any reduction in the maximum response but shifted that of NE to the right with reduction in maximum response. And phentolamine, an ${\alpha}-receptor$ blocker, shifted the concentration-response curve of serotonin or NE without any reduction in maximum responses. The $pA_{2}$ values for cyproheptadine against serotonin and NE were $10.35{\pm}0.04$ and $8.45{\pm}0.13$, respectively. The $pA_{2}$ values for phentolamine against serotonin and NE were $6.87{\pm}0.04$ and $8.14{\pm}0.08$, respectively. after the pretreatment with 6-hydroxydopamine, the contraction induced by 100 mM $K^{+}$, tyramine and serotonin reduced to $83.0{\pm}2.0$, $26.8{\pm}6.2$ and $82.0{\pm}3.5%$ of control, respectively. The contraction by serotonin in the $Ca^{2+}$-free Tyrode's solution was increased and sustained with the addition of $Ca^{2+}$ extracellulary. The serotonin-sensitive intracellular $Ca^{2+}$ pool was depleted completely by the pretreatment with NE, but the NE-sensitive intracellular $Ca^{2+}$ pool was depleted partially by the pretreatment with serotonin. From the above results, it is suggested that the contraction induced by serotonin in the renal artery of a rabbit may be due to mechanisms in which serotonin acts directly on specific serotonin receptors and also acts indirectly on ${\alpha}-adrenoceptors$ by displacing NE from neuronal stores.

• 대한약리학회지
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• 제24권2호
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• pp.203-216
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• 1988

돼지, 가표 및 가토의 뇌동맥에서 기저동맥 (basilar artery, BA)과 circle of willis동맥 (WC)의 동맥환을 만들어 혈관수축제와 calcium 길항제의 효과 그리고 내피세포의 역할은 검토하였다. 돼지 BA와 WC에 서 norepinephrine (NE), phenylephrine (PE)및 epinephrine (EP)은 propranolol $10^{-6}M$ 전처리하에서 그리고 KCI, histamine, 5-hydroxytryptamine (5-HT) 및 angiotensin은 모두 용량의존성 수축반응을 일으켰다. 그 최대수축력은 angiotensin에서 가장 적었고, 5-HT에서 가장 강력하였다. KCI 35 mM수축반응은 calcium 길항제로 용량의존성으로 억제되었고, 그 효력은 nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glycerl trinitrate의 순서였다. 5-HT $10^{-5}M$의 수축반응은 nifedipine으로는 용량의존성으로 억제 되었으나 diltiazem과 ISDN으로는 경미한 억제만을 일으켰다. 내피세포동맥환에서 KCI 35 mM의 수축반응은 acetylcholine (ACh)으로 거의 영향받지 않았으나 $PGF_{2{\alpha}}\;10^{-5}M$의 수축반응은 ACh과 adenosine으로 용량의존성으로 억제되었고, 이 내피세포 의존성억제는 nifedipine $10^{-6}M$로는 영향받지 않으나 methylene blue $50\;{\mu}M$로는 현저히 억제되었다. 네피제거동맥환에의 $PGF_{2{\alpha}}$의 수축반응은 ACh의 영향이 없거나 더욱 수축되었다. 내피세포를 제거하지 않은 가토흉부대동맥편을 bath에 함께 넣어주면 ACh의 용량의존성 이완반응이 나타났고 이 이완반응도methylene blue로 억제되었다. 가묘 BA와 WC에서 5-HT와 NE는 용량의존성 수축반응을 일으켰고 ACh도 내피세포 존재유무와 관계없이 강력한 용량의존성 수축반응을 일으켰으며 그 최대수축력은 ACh에서 가장 강력하였다. 내피세포동맥환에서 5-HT $10^{-5}M$의 수축반응은 ACh에 의하여 이완반응없이 더욱 수측되었다. 가토 BA에서 5-HT와 NE는 응량의존성 수축반응을 일으졌고5-HT의 수축반응이 더욱 현저하였다. 내피세포동맥환에서 5-HT $10^{-5}M$의 수축반응은 ACh $10^{-5}M$로 현저하게 이완되있고 이 내피세포의존성 이완반응은 atropine $10^{-7}M$로는 억제되었으나 diltiazem $10^{-6}M$로는 거의 억제되지 않았다. 이상의 실험성적은 돼지와 가토의 뇌동맥에서 ACh은 내피세포-의존성 이완반응을 일으키며그 이완반응은 muscarinic receptor를 통해 나타났고, 가묘뇌동맥에서 ACh은 혈관수축제의 역할을 갖고 있음을 시사하고 있다.

• Korean Journal of Acupuncture
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• 제17권1호
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• pp.75-80
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• 2000

Fructus Aristolochiae has been used in Korea for many centuries as a treatment for various disease.The purpose of the present study is to determine the effect of Fructus Aristolochiae on norepinephrine(NE) induced blood vessel contraction in rabbits. Rabbit(2 kg, male) were killed by $CO_2$ exposure and a segment (8-10mm) of each rabbit was cut into equal segments and mounted in a tissue bath. Contractile force was measured with force displacement transducers under 2-3 g loading tension. The dose of norepinephrine(NE) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for NE ($10^{-6}{\sim}10^{-3}M$). Contractions evoked by NE ($ED_{50}$) were inhibited significantly by Fructus Aristolochiae in abdominal aorta and femoral artery. Fructus Aristolochiae inhibited the relaxation pretreated propranolol and L-NNA in femoral artery. But Fructus Aristolochiae did not effect the relaxation pretreated ODQ in femoral artery and abdominal aorta. These results indicate that Fructus Aristolochiae can relax NE induced contraction of rabbit blood vessel selectively, and that this relaxation relates to nitric oxide synthesis and sympathetic action.