• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.63-68
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• 1998

Nitric oxide (NO)-mediated relaxation in vascular smooth muscle involves not only activation of guanylate cyclase but also hyperpolarization of the membrane. It has been shown that depolarization decreases the [$Ca^{2+}$] sensitivity of myosin light chain kinase in arterial smooth muscle, and nitric oxide (NO)-mediated relaxation was attenuated in this situation. However, why potassium inhibits or attenuates the action of EDRF/NO is not clear. Therefore, we investigated the magnitude of relaxation and cGMP contents using measures known to release NO, such as photorelaxation, photo activated NO-mediated relaxation, and NO-donor (SNP)-mediated relaxation in porcine coronary arterial rings in which contractile conditions were made by different degree of depolarization, i.e., contraction in response to U46619 or U46619 plus KCl. In all cases, the magnitude of relaxation was significantly greater (P＜0.05) in U46619-contracted rings than in U46619+KCl-contracted ones. Although accumulation of cGMP was evident with three measures employed in the present study, no difference was found in cGMP contents between U46619 and U46619+KCl conditions, indicating that the diminished relaxation in KCl containing solution is cGMP-independent mechanism(s). To understand this further, cytosolic $Ca^{2+}$ changes due to NO were compared in rat thoracic aorta by exploiting photoactivated NO using streptozotocin (STZ) that was contracted with either NE or KCl. Fura-3 $[Ca]_{cyt}$ signal caused by NO was small and transient in high $K^+$-, but large and sustained in NE-contracted aorta. The inhibitory potency of STZ expressed in terms of $IC_{50}$ was 5.14 and 3.88 ${\mu}M$ in NE and in high $K^+$, respectively. These results suggest that modification of the cellular mobilization of $Ca^{2+}$ rather than cGMP levels may be an important mechanism for the NO-mediated relaxation when vascular membrane is depolarized, such as atherosclerosis and hypertension.

• Journal of Nutrition and Health
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• 제30권3호
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• pp.244-251
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• 1997

The effects of Artemisia princeps var orientalis(mugwort), Circium japonicum var ussuriense (Unggungqui) on cadiovascular system in hyperlipidemic rats were investgated. Thirty rats devided into 5 experimental groups, were fed with the diet contained 1% chlesterol, 0.25% sodium cholate, 10% coconut oil and 5% lard by the same method of previous paper1). Contractile and relaxation responses in the isolated artria and thoracic aortae were measured and the morphological changes of the aortic endotherium from the rats were inspected. The responses of the right atrial to isoproterenol were significantly lower value in Ungungqui powder diet group(UP) and mugwort powder diet group(MP) than the control. The contraction force by injectin of phenylephrine and calcium in isolated thoracic aortae was significantly low value in the UP and the MP groups compaired to the control. The relaxation rate by acetylcholine in isolated thoracic aortae represented significantly higher value in UP than control. The morphological changes of endothelial cell suface was smallest in UP and the damage of endothelium by retarded in MP. Although Ungungqui and mugwort extract diet groups(UE, ME) were advanced, those were less than control.

• 대한한의학회지
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• 제19권2호
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• pp.228-243
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• 1998

This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities were determined. SHCS relaxed the arterial rings which were pre-contracted by phenylephrine(PE). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50}$ of PE on its dose-response curve ruled out the possible interaction of SHCS and ${\alpha}-receptor$. The relaxant effect of SHCS was not affected by removal of endothelium, and pretreatment of the arterial rings with methylene blue or nitro-L-arginine. This results suggest that the action of SHCS is not mediated by endothelium nor soluble guanylate cyclase. SHCS relaxed high $K^{+}-induced$ contractions as well, whereas it failed to relax phorbol ester-induced contractions. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}-free$ solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium-independent manner, and inhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.11.1-11.9
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• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.

• Korean Journal of Acupuncture
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• 제17권1호
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• pp.67-73
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• 2000

The purpose of the present study is to determine the effect of Radix Stemonae on histamine induced tracheal smooth muscle contraction in guinea pigs. Guinea pig(500g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine (His) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine ($10^{-7}∼10^{-4}M$). Contractions evoked by His ($ED_{50}$) were inhibited significantly by Radix Stemonae. In guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was 87.4% (p<0.01) after $100{\mu}l/ml$ Radix Stemonae. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$ Radix Stemonae fell to 16.2% in guinea pig induced by histamine contraction. Indomethacin and methylene blue($10^{-7}M$) did not significantly alter the inhibitory effect of Radix Stemonae. These results indicate that Radix Stemonae can relax histamine induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves sympathetic effects.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.59-64
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• 2012

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, $K^+$ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the $K^+$ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine ($EC_{50}$, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholineinduced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

• 대한약리학회지
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• 제14권1_2호
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• pp.33-40
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• 1978

1. guinea-pig 요관(尿管) 평골근(平滑筋)의 수축(收縮) 및 이완반응(弛緩反應) 연령이 증가(增加)에 의(依)하여 크게 영향(影響)을 받는다는 사실(事實)을 관찰(觀察)하였다. 2. 2-3주, 3개월 및 2-3년 guinea-pig 요관(尿管)을 적출하고 Tyrode 액내(液內)에서 train stimulation법(法)으로 일정(一定)하게 수축반응(收縮反應)을 일으킨다. 3. $Ca^{++}$-free Tyrode 액(液)에서 전기자극(電氣刺戟) 반응(反應)이 소실(消失)된 후(後) $Ca^{++}$ 함유(含有) Tyrode 액(液)을 가(加)하여 야기(惹起)되는 수축반응(收縮反應)의 회복(恢復)에는 3개월(個月) 및 2-3년(年) 요관(尿管)에 비(比)하여 2-3주(週) 요관(尿管)은 훨씬 낮은 농도(濃度)의 $Ca^{++}$을 필요(必要)로 하였으며 비록 2.7mM $Ca^{++}$을 가(加)하여도 2-3주(週) 및 3개월(個月) 요관에 있어서는 처음 수축고의 90% 이상을 회복하였으나 2-3년(年) 요관(尿管)에서는 77.2%만 회복하였다. 4. ISP는 2-3년 요관(尿管)에 비(比)하여 2-3주(適) 요관(尿管)에 있어서 수축고의 억제(抑制) 효과(效果)가 유의(有意)하게 강(强)하였고 theophylline은 연령(年齡)에 관계없이 양군(兩群)모두 강력(强力)히 억제작용(抑制作用)을 나타내었다. 5. 2-3주 뇨관의 수축에 대하여 dibutyryl cyclic AMP는 dose-dependent하게 억제를 나타내었으나 2-3년 노요관(老尿管)에 있어서는 이와같은 현상은 없었다. 그리고 요관(尿管)조직내 cyclic AMP 함량(含量)은 2주기니픽 뇨관에서는 17개월 뇨관에 비(比)하여 73%의 높은 농도를 나타내었고 cyclic GMP의 함량(含量)은 큰 차이를 볼 수 없었다. 6. 유년(幼年) 요관평골근(尿管平滑筋)은 노요관(老尿管)에 비(比)하여 근수축(筋收縮) 및 이완(弛緩)에 관여(關與)하는 $Ca^{++}$의 동원(動員) 및 저장(貯藏)에 있어서 높은 효율성(效率性)을 가지고 있다고 사료(思料)되는 바이다.

• 대한수의학회지
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• 제43권3호
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• pp.415-421
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• 2003

It is now generally accepted that acupuncture is effective in diarrhea caused by bacterial infection. However, its effect on the intestinal smooth muscle dysfunction is not clear. Therefore, we investigated the effect of acupuncture therapy at Jiao-chao (GV-1) on the intestinal muscle dysfunction in weaning piglets orally infected by Escherichia coli. The animals are divided into four groups; 1) E. coli + no-treatment, 2) E. coli + antibiotic, 3) E. coli + acupuncture, 4) normal group. In the three E. coli infected groups, low frequency electrical field stimulation (EFS, 1 Hz) provoked triphasic responses composed of initial relaxation followed by on-contraction and off-contraction. While in the normal group, EFS (1Hz) induced biphasic responses composed of relaxation during the stimulation and off-contraction. At the high frequency (16Hz) EFS, both on-contraction and off-contraction of the E. coli + antibiotic, E. coli + acupuncture and the normal group were larger than those of the E. coli + no-treatment group. In the non-adrenergic non-cholinergic (NANC) condition, only biphasic responses occurred to EFS in all experimental groups and the off-contraction of E. coli + antibiotic, E. coli + acupuncture and the normal group were larger than those of the E. coli + no-treatment group. The response to carbachol of those three groups was also significantly greater than that of the E. coli + no-treatment group. These results suggest that acupuncture is as effective as antibiotic in the dysfunction of colonic circular muscle caused by E. coli infection. The maintenance of contractile neuromuscular transmission seems to be involved in the mechanism of the acupuncture effects on diarrhea.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.11-20
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• 1996

To investigate the properties of cromakalim-opened $K^{+}\;channels$ in aorta of spontaneously hypertensive rats (SHR), the effect of cromakalim on tension was compared in endothelium-rubbed aortic rings from SHR and normotensive Wistar-Kyoto rats (WKY). 1. Cromakalim relaxed the aortic ring contracted by $10^{-7}$ M norepinephrine (NE) dose-dependently, and this relaxant response to cromakalim was blocked by $10^{-5}$ M glybenclamide. 2. Cromakalim also relaxed the contraction induced by high $K^{+}$-solution or 10 mM tetraethylammonium dose-dependently. However, the relaxant response to cromakalim was decreased by raising the $K^{+}$ concentration. 3. SHR aorta exhibited myogenic tone in resting state which was inhibited by cromakalim, verapamil or $Ca^{2+}-free\;PSS.$ Whereas, WKY aorta did not exhibit any myogenic tone in resting state. 4. When aortic rings from both strains were contracted by $20\;mM\;K^{+}\;or\;NE$, relaxant responses to low concentration of cromakalim $(below\;10^{-7}\;M)$ were not different between WKY and SHR, but maximum relaxant response to cromakalim $(above\;3{\times}10^{-7} \;M)$ was greater in SHR than in WKY. 5. When the relaxant response to cromakalim was expressed as percent of maximum relaxation induced by $Ca^{2+}-free\;PSS$, relaxant response to cromakalim in 20 mM $K^{+}-induced$ contraction was not different between WKY and SHR. From the above result, it is suggested that relaxant responses to cromakalim are greater in SHR than WKY, and this may be due to the myogenic tone of aortic rings from SHR.

• 대한수의학회지
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• 제36권3호
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• pp.599-605
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• 1996

This study was designed to examine the mechanism of penile erection in adult bull by analyzing the responses of bovine proximal retractor penile muscle strips(BRP) to electtical field stimulation(EFS), exogenous nitric oxide(NO), NO synthesis precursor(L-arginine), NO synthase inhibitors(L-NAME, L-NMMA), guanylate cyclase inhibitor(methylene blue) and nonspecific potassium channel blocker(tetraethylammonium, TEA) treatments. Isometric tension of BRP was measured using physiograph. Results were summarized as follows: 1. EFS of nonadrenergic noncholinrgic(NANC) nerve in BRP produced frequency-dependent inhibitory responses to the contraction induced by co-treatment of epinephrine, guanethidine and atropine. The inhibitory responses to EFS were blocked by tetrodotoxin(TTX, $1{\mu}M$). 2. Treatment of L-NAME ($10,\;20{\mu}M$) inhibited the relaxation to EFS whereas L-NMMA ($100{\mu}M$) had no effect. 3. Treatment of NO($20,\;40{\mu}M$; as an acidified solution of $NaNO_2$) induced concentration-dependent relaxation whereas preincubation of TTX($1{\mu}M$) and L-NAME($20{\mu}M$) had no effect on the relaxation response. 4. L-arginine treatment(10mM) blocked the inhibitory effect of L-NAME($20{\mu}M$). 5. Pretreatment of methylene blue($40{\mu}M$) reduced the NANC-induced relaxation of BRP. 6. Tetraethylammonium(TEA, 80mM) reduced NANC relaxation. These results suggest that NO may act as a NANC neurotransmitter in BRP and the effects might be mediated by cGMP and potassium channel.