• The Korean Journal of Physiology
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• 제30권2호
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• pp.269-278
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• 1996

The mechanism of impaired endothelium-dependent relaxation in the aorta of one-kidney, one clip Goldblatt hypertensive (1K,1C-GBH) rats was investigated. 8 week-old Wistar-Kyoto (WKY) rats were made hypertensive by left renal artery stenosis with contralateral nephrectomy. Endothelium-dependent relaxation was significantly reduced in 1K,1C-GBH rats as compared with WKY rats. However, the relaxation by sodium nitroprusside in 1K,1C-GBH rats was not reduced as compared with WKY rats. The impairment of endothelium-dependent relaxation in 1K,1C-GBH rats was partially restored by the pretreatment of indomethacin or SQ29548. When the nitric oxide production was inhibited by L-nitroarginine methyl ester, acetylcholine (ACh) induced a endothelium-dependent contraction that was greater in 1K,1C-GBH rats than in WKY rats. Endothelium-dependent contraction by ACh was completely abolished by indomethacin or SQ29548. However, imidazole, tranylcypromine and superoxide dismutase did not affect the endothelium-dependent contraction in 1K,1C-GBH rats. These results suggest that impaired endothelium-dependent relaxation in the 1K,1C-GBH rats might be due to the simultaneous release of EDCF, and that prostaglandin B2 may be involved as a mediator of endothelium-dependent contraction.

• 대한치과마취과학회지
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• 제6권2호
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• pp.121-126
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• 2006

Generalized anaphylaxis is a most dramatic and acutely life-threatening allergic reaction. Most fatalities from anaphylaxis occur within the first 30 minutes postantigenic exposure. The mechanism of generalized anaphylaxis is the reaction of IgE antibodies to an allergen that causes the release of histamine, bradykinin, and others. These chemical mediators cause the contraction of smooth muscles of the respiratory and intestinal tracts, as well as increased vascular permeability. Four major clinical symptoms are recognized: skin reactions, smooth muscle spasm (gastrointestinal and genitourinary tracts and respiratory smooth muscle), respiratory distress, and cardiovascular collapse. Epinephrine is the drug of choice for the management. Its syrnpathomimetic effects directly counteract most aspects of the attack. Respiration must be immediately supported by the establishment of a patent airway along with artificial ventilation. The circulation should be supported and the existing hypotension overcome by placing the victim in a position to allow gravity to aid venous return and by administering intravenous fluids, vasopressors, and corticosteroids. When an imperceptible pulse is evident, external cardiac compression must also be instituted. This is a case report of anaphylactic shock care during general anesthesia, possibly due to penicillin, pancuronium and others.

• The Journal of Korean Physical Therapy
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• 제14권4호
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• pp.454-474
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• 2002

Vasoactive intestinal peptide (VIP) is a very potent dilatator and a nonadrenergic, noncholinergic (NANC) neurotransmitter or neuromodulator in the peripheral and the central nervous systems. The mechanisms of action of VIP were examined in aortic circular and in uterine longitudinal smooth muscle strips of the rat. The effects of sympathetic neurotransmitter were investigated in gastric and aortic circular muscle strips of the mouse and the rat. The effects of silver spike point, SSP, low frequency electrical stimulations of VIP, sympathetic neurotransmitter and $\beta$-endorphin were examined in plasma, serum and 24h urine from the healthy volunteer. In gastric smooth muscle strips from the mouse, adrenergic neurotransmitter norepinephrine was inhibitory effected, followed by caused phasic and tonic contraction to the, muscrine receptor agonist carbachol and acetylcholine, respectively. In urine from the healthy volunteer, both norepinephrine and epinephrine were significantly decreased in continue type and low frequency (3 Hz) of SSP electrical stimulations. The contractile responses to S-HT in uterine longitudinal smooth muscle strips of the rats were completely decreased by a VIP 1 $\mu$M. The contractile responses to PGF2$\alpha$ were not decreased by a VIP. In plasma and serum from the healthy volunteer, both VIP and $\beta$-endorphin were significantly increased in continue type and low frequency (3 Hz) of SSP electrical stimulations. Therefore, this study demonstrate that VIP has the capacity to relax vascular or gastric smooth muscles in part by stimulating the generation of NO, and silver spike point low frequency electrical stimulation has the capacity both to decrease sympathetic neurotransmitters and to increase VIP, $\beta$-endorphin.

• 대한약리학회지
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• 제15권1_2호
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• pp.29-37
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• 1979

Cd 중독(中毒)으로 가토(家兎)에 고혈압(高血壓)을 일으키고 이를 중독(中毒) 가토(家兎)와 대조(對照) 비중독(非中毒) 가토(家兎)의 간문맥(肝門脈), 흉부(胸部) 대정맥(大動脈) 및 폐정맥(肺動脈)을 적출하여 in vitro에서 장력(張力)-길이의 관계를 관찰하고 NE, $K^+$-depolariration 및 angiotensin의 수축(收縮) 효과(效果)를 비교(比較)하였다. 1. 비중독(非中毒) 대조군의 평균 동맥압은 $87.0{\pm}4.7mmHg$이었고 Cd 중독군(中毒群)에서는 $109.0{\pm}2.8mmHg$로 Cd 중독(中毒)에 의하여 의의(意義)있는 증가(增加)를 나타내었다. 2. 동(動) 정맥(靜脈)의 장력(張力)-길이 곡선(曲線)에서 Cd 중독(中毒) 가토의 간문맥(肝門脈)은 passive tension의 증가에 따라 distensibility가 현저히 증가되나 대동맥(大動脈)에 있어서는 오히려 대조군에 비(比)하여 유의(有意)한 감소(減少)를 나타내었고 폐동맥(肺動脈)은 아무런 차이(差異)를 나타내지 아니하였다. 3. Passive tension의 증가에 따른 active tension의 변화(變化)는 대동맥(大動脈)에 있어서는 Cd중독으로 현저히 감약되었으나 간문맥(肝門脈)이나 폐동맥(肺動脈)은 대조군과 별다른 차이(差異)가 없었다. 4. Cd 중독군(中毒群)이나 비중독(非中毒) 대조군에서 passive tension의 변동에 따른 수축결과(收縮效果)는 세 혈관에서 모두 유의(有意)한 차이를 나타내지 아니하였다. 5. 대동맥(大動脈) 절편에 대한 angiotensin의 수축(收縮) 효과(效果)는 Cd 중독군(中毒群)에서 유의하게 저하되었다.

• Archives of Pharmacal Research
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• 제29권11호
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• pp.1024-1031
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• 2006

The role of mitogen-activated protein kinase (MAPK) in the decreased contractile response to phorbol ester in aortic smooth muscle strips from deoxycorticosterone acetate (DOCA)-salt hypertensive rats was examined. Norepinephrine (NE) evoked greater contractility in aortic strips from DOCA rats than in those of sham-operated rats. 12-Deoxyphorbol 13-isobutyrate (DPB) induced contraction in $Ca^{2+}-free$ medium, which was diminished in strips from DOCA rats compared to sham-operated rats. Vasoconstrictions induced by these stimulants were inhibited by SB203580 and PD098059, inhibitors of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2, respectively, in both strips. The phosphorylation of p38 MAPK and ERK1/2 induced by NE was greater in strips from DOCA rats compared to those from sham-operated rats, and this phosphorylation was inhibited by the kinase inhibitors. DPB increased the phosphorylation of p38 MAPK and ERK1/2 in strips from both animals, and the increment of p38 MAPK phosphorylation by the stimulant was diminished in strips from DOCA rats compared to sham-operated rats. These findings suggest that the $Ca^{2+}-independent$ contraction evoked by DPB results from the activation of MAPKs in rat aortic smooth muscle and that the attenuated contractility by DPB in DOCA rat appears to be associated with diminished p38 MAPK activity.

• 한국축산식품학회지
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• 제44권1호
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• pp.216-224
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• 2024

The reduction of nitric oxide (NO) bioavailability in the endothelium induces endothelial dysfunction, contributing to the development of hypertension. Although Lactobacillus consumption decreases blood pressure, intracellular signaling pathways related to hypertension have not been well elucidated. Thus, this study examined the effect of spray-dried Lactiplantibacillus plantarum K79 (LpK79) on NO production, intracellular signaling pathways, and inflammatory responses related to vascular function and hypertension. NO production was assessed in human umbilical vein endothelial cells (HUVECs) treated with LpK79. Endothelial NO synthase (eNOS) and intracellular signaling molecules were determined using Western blot analysis. LpK79 dose-dependently increased NO production and activated eNOS via the phosphoinositide 3-kinase/Akt signaling pathway HUVECs. Moreover, LpK79 mitigated the activation of crucial factors pivotal for vascular contraction in smooth muscle cells, such as phospholipase Cγ, myosin phosphatase target subunit 1, and Rho-associated kinase 2. When HUVECs were treated with LpL79 in the presence of Escherichia coli lipopolysaccharide (LPS), LpK79 effectively suppressed mRNA and protein expression of pro-inflammatory mediators induced by E. coli LPS. These results suggest that LpK79 provided a beneficial effect on the regulation of vascular endothelial function.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.463-469
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• 2000

It has been well known that 4-aminopyridine (4-AP) has an excitatory effect on vascular smooth muscle due to causing membrane depolarization by blocking $K^+-channel$. However, we observed that 4-AP had an inhibitory effect on the mesenteric artery of rat. Therefore, we investigated the mechanism of 4-AP-induced vasorelaxation. The mesenteric arcuate artery and its branches were isolated and cut into ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured. 4-AP $(0.1{\sim}10\;mM)$ induced a concentration-dependent relaxation, which was unaffected by NO synthase inhibitor, $N^G-nitro-L-arginine$ methylester $(100\;{\mu}M)$ or soluble guanylate cyclase inhibitor, methylene blue $(100\;{\mu}M).$ Glibenclamide $(100\;{\mu}M)$, ATP-sensitive $K^+$ channel blocker, did not exert any effect on the 4-AP-induced vasorelaxation. 4-AP relaxed the sustained contraction induced by 100 mM $K^+$ or $Ca^{2+}$ ionophore, A23187 $(100\;{\mu}M)$ in a dose-dependent manner. In addition, 4-AP significantly decreased the phasic contractile response to norepinephrine in the absence of extracellular $Ca^{2+}$. However, 4-AP did not block the $^{45}Ca$ influx of rat aorta. From the above results, we suggest that 4-AP may not block the $Ca^{2+}$ influx through $Ca^{2+}-channel,$ but act as a nonspecific vasorelaxant in arterial smooth muscle.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.769-774
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• 1997

Non-neuronal high affinity binding sites for benzodiazepines have been found in many peripheral tissues including cardiac muscle and vascular smooth muscle, and have been designated as 'peripheral benzodiazepine receptor'. Benzodiazepines have been shown to induce relaxation of the ileal, vesical, and uterine smooth muscles. However, it is still unclear about possible involvement of peripheral benzodiazepine receptor on the contractility of trachealis muscle. This study was performed to investigate the role of the peripheral benzodiazepine receptor on the contractility of canine trachealis muscle. Canine trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiological salt solution maintained at $37^{\circ}C$, and aerated with $95%\;O_2/5%\;CO_2$. Isometric myography was performed, and the results of the experiments were as follows: Ro5-4684, FGIN-1-27 and clonazepam reduced a basal tone of isolated canine trachealis muscle strip concentration dependently, relaxant actions of RoS-4684 and FGIN-1-27 were antagonized by PK11195, a peripheral benzodiazepine receptor antagonist. Flumazenil, a central type antagonist, did not antagonize the relaxant action of Peripheral type agonists. Saturation binding assay of [3H]Ro5-4864 showed a high affinity$(Kd=5.33{\pm}1.27nM,\;Bmax=\;867.3{\pm}147.2\;fmol/mg\;protein)$ binding site on the canine trachealis muscle. Ro 5-4684 suppressed the bethanechol-, 5-hydroxyoyptamine- and histamine- induced contractions. Platelet activating factor (PAF) exerted strong and prolonged contraction in trachealis muscle strip. Strong tonic contraction by PAE was attenuated by Ro 5-4684, but not by WEB 2086, a PAF antagonist. Based on these results, it is concluded that the peripheral benzodiazepine receptor mediates the inhibitory regulation of contractilty of canine trachealis muscle.

• The Korean Journal of Physiology
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• 제16권1호
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• pp.1-11
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• 1982

Force development of smooth muscle cells is directly regulated by the concentration of free calcium ions in the sarcoplasm, and the sarcoplasmic concentration of calcium ion can be modulated by electrogenic Na-K pump. The role of Na-K pump on vascular tone was studied in isolated rabbit renal artery. Helical strips of arterial muscle were prepared from left renal arteries. All experiments were performed in $HCO_3^--buffered$ Tyrode solution which was aerated with $3%CO_2-97%\;O_2$ mixed gas and kept at $35^{\circ}C$. In some experiments, rabbit was injected intraperitoneally $18{\sim}24$ hours prior to the experiments, with a large dose(5 mg/kg body wt) of reserpine, in order to eliminate the catecholamines present in intrinsic adrenergic nerve terminate. Treatment used in this experiment that inhibits Na-K pump was the exposure of strips to K-free Tyrode solution. Contractile response to K free Tyrode solution developed slowly and the time required for maximum contracture was $20{\sim}30$ minutes. This K-free contracture was rapidly relaxed by the addition of potassium to the bathing solution. No K-free contracture occurred in a Ca-free Tyrode solution. But contraction developed rapidly when calcium ion was added to the bathing solution after 30 minute exposure of the strip to Ca-free Tyrode solution. This contracture was completely inhibited by Ca-antagonist, verapamil. The K-free contracture was abolished by ${\alpha}-adrenergic$ blocker, phentolamine, as well as by the catecholamine depletion from adrenergic nerve terminals. Even in reserpinized strip, the exogenous norepinephrine-induced contraction in K-free Tyrode solution was rapidly suppressed by the addition of potassium ion. The results of this experiment suggest that K free contracture develops by norepinephrine release from adrenergic nerve terminals, while the relaxation of K-free contracture is induced by the activation of electrogenic Na-K pump.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.49-57
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• 2024

While arterial tone is generally determined by the phosphorylation of Ser¹⁹ in myosin light chain (p-MLC2), Thr¹⁸/Ser¹⁹ diphosphorylation of MLC2 (pp-MLC2) has been suggested to hinder the relaxation of smooth muscle. In a dual-wire myography of rodent pulmonary artery (PA) and mesenteric artery (MA), we noticed significantly slower relaxation in PA than in MA after 80 mM KCl-induced condition (80K-contraction). Thus, we investigated the MLC2 phosphorylation and the expression levels of its regulatory enzymes; soluble guanylate cyclase (sGC), Rho-A dependent kinase (ROCK) and myosin light chain phosphatase target regulatory subunit (MYPT1). Immunoblotting showed higher sGC-α and ROCK2 in PA than MA, while sGC-β and MYPT1 levels were higher in MA than in PA. Interestingly, the level of pp-MLC2 was higher in PA than in MA without stimulation. In the 80K-contraction state, the levels of p-MLC2 and pp-MLC2 were commonly increased. Treatment with the ROCK inhibitor (Y27632, 10 µM) reversed the higher pp-MLC2 in PA. In the myography study, pharmacological inhibition of sGC (ODQ, 10 µM) slowed relaxation during washout, which was more pronounced in PA than in MA. The simultaneous treatment of Y27632 and ODQ reversed the impaired relaxation in PA and MA. Although treatment of PA with Y27632 alone could increase the rate of relaxation, it was still slower than that of MA without Y27632 treatment. Taken together, we suggest that the higher ROCK and lower MYPT in PA would have induced the higher level of MLC2 phosphorylation, which is responsible for the characteristic slow relaxation in PA.