• 대한수의학회지
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• 제27권2호
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• pp.201-206
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• 1987

This study was carried out to investigate the action of ATP, which has been known as the neurotransmitter of noncholinergic- and nonadrenergic-nerve, on the motility of immature pig uterine smooth muscle. The results were summarized as follows; 1. The contraction and the contractile responses caused by ATP were increased in a dose-dependent manner between the concentration of ATP $10^{-6}M$ and $10^{-3}M$. The maximal contractile effect was appeared at the concentration of ATP $10^{-3}M$ and it was 70.2% of 100mM K contraction. 2. The contractile responses induced by ATP ($10^{-4}M$) were not blocked by the pretreatment with cholinergic receptor blocker, atropine ($10^{-6}M$). 3. The contractile responses induced by ATP ($10^{-4}M$) were not blocked by pretreatment with ${\alpha}$-adrenergic receptor blocker, phentolamine ($10^{-6}M$) and ${\beta}$-adrenergic receptor blocker, propranolol ($10^{-6}M$). 4. The contractile response induced by ATP ($10^{-4}M$) was not blocked by the pretreatment with $H_1-receptor$ blocker, pyrilamine ($10^{-6}M$) and $H_2-receptor$ blocker, cimetidine ($10^{-6}M$).

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.119-124
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• 2006

This study was performed to investigate the influence of the spinal adenosine $A_1$ receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by cyclic AMP (cAMP), cyclic GMP (cGMP) or potassium channel. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. I.t. injection of adenosine $A_1$ receptor agonist, $N^6$-cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR and it was attenuated by pretreatment of 50 nmol of 8-cyclopentyl-1,3-dimethylxanthine, a specific adenosine $A_1$ receptor antagonist. Pretreatment with a cAMP analogue, 8-bromo-cAMP, also attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. Pretreatment with a ATP-sensitive potassium channel blocker, glipizide (20 nmol) also attenuated the depressor and bradycardiac effects of CHA (10 nmol). These results suggest that adenosine $A_1$ receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that this depressor and bradycardiac actions are mediated by cAMP and potassium channel.

• 한국동물위생학회지
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• 제17권3호
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• pp.247-254
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• 1994

To elucidate the action of the cholinergic nerve on the isolated uterine smooth muscle of the pig, effects of electrical transmural nerve stimulation and acetylcholine were investigated on the pretreatment of the physostigmine ; cholinestrase inhibitor and atropine ; cholinergic receptor blocker from physiograph. 1. The contractile response induced by acetylcholine was responsed in the concentration of 10^{-8}$ M at first and the maximum contractility was concentration of $10^{-6}$ M. 2. The contractile response induced by electrical transmural nerve stimulation(20 V, 0.5 Msec, 20 sec) was the frequency(2-64 Hz) -dependent manner. 3. The contractile response induced by acetylcholine was completely blocked by the pretreatment with cholinergic receptor blocker, atropine and was increased by the pretrement of cholinestrase inhibitor, physostigmine. 4. The contractile response induced by electrical transmural nerve stimulation was completely blocked by the pretreatment with cholinergic receptor blocker, atropine, and was increased by the pretretment of cholinestrase inhibitor, physostigmine. These findings suggest that it was powerful excitatory action by cholinergic nerve on uterine smooth muscle of the pig.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.447-456
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• 2018

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) ($576{\mu}g/kg/day$) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor ($AT_2R$) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as $TNF-{\alpha}$, MCP-1, $IL-1{\beta}$, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via $AT_2R$.

• 한국방사선학회논문지
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• 제13권3호
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• pp.359-369
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• 2019

관상동맥 스텐트 혈전증 치료에 있어서 혈소판 당단백 IIb/IIIa 수용체 차단제와 카테터를 이용한 혈전 흡입술을 동시에 시행한 경우의 효과에 대하여 알아보고자 하였다. 2008년 07월부터 2017년 07월까지의 일대학교병원 심혈관센터에서 경피적 관상동맥 스텐트 삽입술 후 관상동맥 조영술에서 스텐트 혈전증이 발생한 환자 267명($64.6{\pm}12.1$년, 187남자) 그룹 I(혈전용해술과 혈전흡입술 동시 시행한 경우, n=32명), 그룹 II(혈전용해술이나 혈전흡입술 한 가지만 시행한 경우 혹은 둘 다 시행하지 않은 경우, n=235명)로 분류하여 주요심장사건, 사망 발생률, 표적병변 재개통술 그리고 스텐트 혈전 등을 1 년동안 추적 관찰하였다. 두 군간에 임상 특성에서 연령(그룹I: $60.8{\pm}12.9$ vs. 그룹II: $65.1{\pm}11.9$, p=0.603), 남성(그룹I: 75.0% vs. 그룹II: 69.4%, p=0.681), 좌심실구혈율(그룹I: $58.1{\pm}9.0$ vs. 그룹II: $59.5{\pm}11.9$, p=0.127)등 양군 간에 차이는 없었다. 주요 심장사건은 두 군간에 차이를 보이지 않았으나(그룹I: 12.5% vs. 그룹II: 23.8%, p=0.180), 세부적으로 살펴보면 사망발생률(그룹I: 0% vs. 그룹II: 13.2%, p=0.034), 표적병변 재개통술(그룹I: 9.4% vs. 그룹II: 6.4%, p=0.461) 그리고 스텐트 혈전증(그룹I: 3.1% vs. 그룹II: 4.7%, p=1000)으로, 사망발생률은 혈소판 당단백 IIb/IIIa 수용체 차단제와 혈전흡입술을 동시에 시행한 군에서 유의하게 낮았다. 결론적으로, 관상동맥 스텐트 혈전증 치료에 있어 혈전용해술과 혈전흡입술을 동시 시행하는 경우에 비교군보다 사망 발생율을 감소시켰다.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.328-336
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• 2020

Diabetes mellitus affects the colonic motility developing gastrointestinal symptoms, such as constipation. The aim of the study was to examine the role of intracellular signaling pathways contributing to colonic dysmotility in diabetes mellitus. To generate diabetes mellitus, the rats were injected by a single high dose of streptozotocin (65 mg/kg) intraperitoneally. The proximal colons from both normal and diabetic rats were contracted by applying an electrical field stimulation with pulse voltage of 40 V in amplitude and pulse duration of 1 ms at frequencies of 1, 2, 4, and 6 Hz. The muscle strips from both normal rats and rats with diabetes mellitus were pretreated with different antagonists and inhibitors. Rats with diabetes mellitus had lower motility than the control group. There were significant differences in the percentage of inhibition of contraction between normal rats and rats with diabetes mellitus after the incubation of tetrodotoxin (neuronal blocker), atropine (muscarinic receptor antagonist), prazosin (α₁ adrenergic receptor antagonist), DPCPX (adenosine A1 receptor antagonist), verapamil (L-type Ca²⁺ channel blocker), U73122 (PLC inhibitor), ML-9 (MLCK inhibitor), udenafil (PDE₅ inhibitor), and methylene blue (guanylate cyclase inhibitor). The protein expression of p-MLC and PDE₅ were decreased in the diabetic group compared to the normal group. These results showed that the reduced colonic contractility resulted from the impaired neuronal conduction and decreased muscarinic receptor sensitivity, which resulted in decreased phosphorylation of MLC via MLCK, and cGMP activity through PDE₅.

• 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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• 제16권2호
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

• Journal of Preventive Medicine and Public Health
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• 제53권6호
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• pp.476-486
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• 2020

Objectives: The objective of this study was to estimate the risk of lung cancer in relation to angiotensin II receptor blocker (ARB) use among patients with hypertension from the Korean National Health Insurance Service-National Health Screening Cohort. Methods: We conducted a retrospective cohort study of patients with hypertension who started to take antihypertensive medications and had a treatment period of at least 6 months. We calculated the weighted hazard ratios (HRs) and their 95% confidence intervals (CIs) of lung cancer associated with ARB use compared with calcium channel blocker (CCB) use using inverse probability treatment weighting. Results: Among a total of 60 469 subjects with a median follow-up time of 7.8 years, 476 cases of lung cancer were identified. ARB use had a protective effect on lung cancer compared with CCB use (HR, 0.75; 95% CI, 0.59 to 0.96). Consistent findings were found in analyses considering patients who changed or discontinued their medication (HR, 0.50; 95% CI, 0.32 to 0.77), as well as for women (HR, 0.56; 95% CI, 0.34 to 0.93), patients without chronic obstructive pulmonary disease (HR, 0.75; 95% CI, 0.56 to 1.00), never-smokers (HR, 0.64; 95% CI, 0.42 to 0.99), and non-drinkers (HR, 0.69; 95% CI, 0.49 to 0.97). In analyses with different comparison antihypertensive medications, the overall protective effects of ARBs on lung cancer risk remained consistent. Conclusions: The results of the present study suggest that ARBs could decrease the risk of lung cancer. More evidence is needed to establish the causal effect of ARBs on the incidence of lung cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.99-109
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• 2013

The aim of this study was to determine whether fimasartan, a newly developed $AT_1$ receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 ${\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), and veratridine (100 ${\mu}M$, an activator of $Na^+$ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 ${\mu}M$) and L-NAME (30 ${\mu}M$, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high $K^+$, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 ${\mu}M$) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 ${\mu}M$). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is relevant to $AT_1$ receptor blockade without NO release.