• Radiation Oncology Journal
• /
• 제22권1호
• /
• pp.40-54
• /
• 2004

목적 : 정상 흰쥐의 심장에 방사선을 조사한 군과 captopril과 방사선 조사를 병용한 군의 병리학적 소견과 $TNF-{\alpha}$ (tumor necrosis factor-alpha), $TGF-{\beta}1$ (transforming growth factor-beta), PDGF (platelet-derived growth factor), FGF (fibrobiast growth factor)-2의 발현상태를 비교 관찰함으로써 심장의 조기 방사선손상에서 captopril의 효과와 보호기전에서의 사이토카인의 역할을 알아보고자 하였다. 대상 및 방법 : 실험동물(Sprague-Dawley-Dawley 흰쥐)은 대조군, 방사선 조사 단독군, captopril과 방사선 조사 병용군으로 분류하였다. 방사선 조사 단독군은 12.5 Gy의 X-선을 좌흉곽에 단일 조사하였다. Captopril과 방사선 조사 병용군은 1일 50 mg/kg의 captopril을 방사선조사 1주 전부터 실험종료 시인 8주 후까지 식수에 섞어 음용시켰다. 실험 결과는 방사선조사 2주와 8주 후에 심방과 심실의 병리조직 소견을 비교 관찰하였고 면역조직화학염색으로 $TNF-{\alpha}$, $TGF-{\beta}$1, PDGF, FGG-2의 발현을 관찰하였다. 결과 : 방사선조사 2주 후 병리조직 소견상 대조군에 비해 심한 심방 심장막(pericardium) 섬유소 침착(p=0.093), 심실 혈관주위(perivascular space) 부종(p=0.082)과 혈관주위 및 사이질(interstitium)의 섬유소 침착(p=0.018)이 보였으며, 심방 심장막의 섬유소 침착은 심실에 비해 현저하였다(p=0.009). 방사선 조사 후 8주의 변화는 2주 소견에 비해서 부종 및 섬유소 침착은 소멸되었고, 섬유화가 관찰되었는데 이는 심실보다 심방의 심장막에서 현저하게 나타났다. Captopril과 방사선 병용군은 방사선에 의한 심장손상이 감소되어 병리학적 소견상 대조군과 비교 시 유의한 차이가 없었고, 방사선 조사 단독군과 비교하여 특히 2주 후에 심방의 심내막(endocardium) 섬유소 침착(p=0.047)과 심실의 사이질 섬유소 침착(p=0.019) 및 부종(p=0.042)이 현저히 감소되었다. 방사선조사 2주 후에 $TNF-{\alpha}$, $TGF-{\beta}$1, PDGF, FGF-2의 발현이 방사선 조사 단독군에서 대조군과 비교하여 증가되었으며, 특히 심방의 심장막 및 심장내막에서 현저하게 증가되었다. 방사선조사 8주 후에는 심장막의 $TNF-{\lapha}$, $TGF-{\beta}$1이 계속 증가되었으며 $TGF-{\beta}1$는 심방 심내막(p=0.015)과 사이질(p=0.025)에서 특히 증가되었으나, PDGF와 FGF-2는 감소되었다. Captopril과 방사선조사 병용군은 2주에 방사선 조사 단독군에 비하여 $TNF-{\alpha}$, $TGF-{\beta}$l, PDGF의 발현이 감소되었으며, 8주에는 심방과 심실의 심장막에서 $TNF-{\alpha}$가 현저히 감소되었고(p=0.049, p=0.009) $TGF-{\beta}1$, PDGF의 경우 감소되는 경향을 보였으나 유의한 차이는 없었다. 결론 : 흰쥐의 심장에 captopril을 방사선과 병용 투여하여 병리조직 소견을 관찰한 결과 방사선에 의한 조기 심장 손상이 감소됨을 확인할 수 있었다. 또한 방사선조사 후 2주 및 8주에 병용군에서 단독군에 비하여 $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF 등의 발현이 감소하는 양상이 관찰되어, captopril이 사이토카인의 발현을 억제함으로써 방사선에 의한 심장손상을 감소시킬 수 있을 것으로 생각된다.

• 대한약리학회지
• /
• 제29권2호
• /
• pp.237-244
• /
• 1993

소 부신수실 크롬친화성 세포(BAMC)에서 $[Met^5]-enkephalin$ (ME)의 분비와 Proenkephalin A (proENK) mRNA의 함량에 대한 nicotine의 영향과 이에 대한 indomethacin, nordihydroguaiaretic acid(NDGA) 및 captopril의 작용을 연구하였다. 10 uM Nicotine으로 BAMC 세포를 장기간 자극시 proENK mRNA의 함량과 배양액으로의 ME 분비가 유의하게 증가하였다. BAMC 세포를 NDGA(lipoxygenase 억제제, 10 uM), indomethacin (cyclooxygenase 억제제), captopril (angiotensin 변환효소 억제제)만으로 처리시에는 ME 분비와 proENK mRNA의 함량에 영향이 없었다. Nicotine에 의한 ME 분비와 proENK mRNA 함량의 증가는 NDGA에 의하여 억제되었다. 그러나 indomethacin과 captopril은 nicotine의 작용에 대하여 아무 영향이 없었다. 이들 결과는 nicotine에 의한 ME 분비와 proENK mRNA 함량의 증가가 부분적으로 lipoxygenase 경로에 의해 매개되며, cyclooxygenase 및 내재성 renin-angiotensin 경로는 관련되지 않음을 나타낸다.

• Journal of Veterinary Science
• /
• 제24권2호
• /
• pp.26.1-26.11
• /
• 2023

Background: Angiotensin-converting enzyme inhibitor (ACEi) inhibits the catalysis of angiotensin I to angiotensin II and the degradation of substance P (SP) and bradykinin (BK). While the possible relationship between ACEi and SP in nociceptive mice was recently suggested, the effect of ACEi on signal transduction in astrocytes remains unclear. Objectives: This study examined whether ACE inhibition with captopril or enalapril modulates the levels of SP and BK in primary cultured astrocytes and whether this change modulates PKC isoforms (PKCα, PKCβI, and PKCε) expression in cultured astrocytes. Methods: Immunocytochemistry and Western blot analysis were performed to examine the changes in the levels of SP and BK and the expression of the PKC isoforms in primary cultured astrocytes, respectively. Results: The treatment of captopril or enalapril increased the immunoreactivity of SP and BK significantly in glial fibrillary acidic protein-positive cultured astrocytes. These increases were suppressed by a pretreatment with an angiotensin-converting enzyme. In addition, treatment with captopril increased the expression of the PKCβI isoform in cultured astrocytes, while there were no changes in the expression of the PKCα and PKCε isoforms after the captopril treatment. The captopril-induced increased expression of the PKCβI isoform was inhibited by a pretreatment with the neurokinin-1 receptor antagonist, L-733,060, the BK B1 receptor antagonist, R 715, or the BK B₂ receptor antagonist, HOE 140. Conclusions: These results suggest that ACE inhibition with captopril or enalapril increases the levels of SP and BK in cultured astrocytes and that the activation of SP and BK receptors mediates the captopril-induced increase in the expression of the PKCβI isoform.

• Radiation Oncology Journal
• /
• 제34권3호
• /
• pp.223-229
• /
• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• Journal of Yeungnam Medical Science
• /
• 제14권2호
• /
• pp.474-482
• /
• 1997

There have been some case reports of the coexistence of extraadrenal pheochromocytoma and renal artery stenosis. Some reporters proposed that their coexistence may be associated through a common pathophysiological mechanism mediated by catecholamine secretion. Also some noted that trasient renal artery stenosis due to a spasm was induced by the catecholamines released from pheochromacytoma. We report a case of left paraaortic extraadrenal pheochromacytoma that had a transient oral captopril test positive result. After 5 days ${\alpha}$-antagonist reduced the vasospastic response of catecholamines. After surgical removal of the tumor, plasma catecholamines and urinary vanillyhnandelic acid concentrations as well as the blood pressure level, were restored to normal.

• Journal of Pharmaceutical Investigation
• /
• 제28권1호
• /
• pp.7-13
• /
• 1998

The captopril microcapsules were prepared and were investigated by measuring their size distribution using Scanning Electron Microscopy(SEM) and dissolution of captopril. Cetyl alcohol microcapsules prepared by emulsion melted-cooled method with various ratios of drug to cetyl alcohol were spherical and uniform. The release rate of cetyl alcohol microcapsules was decreased proportionally as the content of cetyl alcohol increased but, the particle size of microcapsules was increased. The surface of cetyl alcohol microcapsules was comparatively rough as drug content increased. Pellet type microcapsules were prepared using fluidized-bed coating system by spraying captopril solution on nonpareil-seeds followed by applying $Eudragit^{\circledR}$ RS solution containing propylene glycol as a plasticizer. The release rate of drug from pellet type microcapsules decreased as the content of $Eudragit^{\circledR}$ RS increased.

• 대한핵의학회지
• /
• 제26권2호
• /
• pp.312-317
• /
• 1992

To evaluate the sensitivity and specificity of captopril renal scan for renovascular hypertension, we employed the captopril renal scan in conjunction with renal angiography in 81 patients, 159 kidneys, who were referred to evaluate the cause of hypertension. We defined the renovascular hypertension by the criteria of demonstration of renal artery stenosis by angiography, and improvement or cure of hypertension by revascularization. Visual and quantitative evaluation of $^{99m}Tc-DTPA$ renal scan was peformed pre and post captopril administration. The prevalence rate of renovascular hypertension was 40% in comparing with renal angiography, and 70% in confirmed cases. The causes of renovascular hypertension in 81 patients were Takayasu's arteritis, fibromuscular dysplasia, atherosclerosis, essential hypertension, chronic pyetonephritis etc. The sensitivity and specificity of captopril renal scan in comparing with renal angiography were 80%, 86.5%, respectively and also 84.2%, 72.6% in confirmed cases of renovascular hypertension, respectively. The causes of false negative cases were nonfunctioning kidney due to complete obstruction or long duration of disease in basal scan, segmental branch artery stenosis, unknown causes, and suspicious true negative cases without confirmation. The false positive cases were abdominal aortic stenosis or aneurysm, dehydration, unknown causes, and suspicious true positive cases. We conclude that captopril renal scintigraphy is highly sensitive, reasonably specific diagnostic method and comparable to other techniques very favorably.

• 대한핵의학회지
• /
• 제24권2호
• /
• pp.325-331
• /
• 1990

Radionuclide renal scintigraphies were performed in a 24-year-old man with right renal artery branch stenosis. Captopril enhanced $^{99m}Tc-DTPA$ renal scintigraphy revealed no abnormal finding in the right kidney. But, $^{99m}Tc-DMSA$ renal scintigraphy showed regional cortical photon deficient area corresponding to the area supplied by the stenotic branch artery. The defect size increased in captopril enhanced $^{99m}Tc-DMSA$ renal scintigrphy and nearly disappeared after successful transluminal renal angioplasty. This case suggests that the captopril enhanced $^{99m}Tc-DMSA$ renal scintigraphy may be a useful method in the evaluation of renovascular hypertension, especially due to branch renal srtery stenosis.

• Archives of Pharmacal Research
• /
• 제19권5호
• /
• pp.390-395
• /
• 1996

To investigate whether $AT_{1}$ receptor antagonists are acting by increasing endothelium-de-pendent and -independent relaxation of aortas in normotensive rats, $AT_{1}$ receptor antagonists, losartan and KR-30988, and angiotensin converting enzyme inhibitor, captopril, were orally administered for two weeks (50 mg/kg, b.i.d.). THe blood pressure, heart rate and body weight were not significantly changed by losartan, KR-30988 and captopril compared to the control group. In aortic preparations, the $pD_{2}$ of KR-30988 for ACh-induced relaxation was 8.33 $\pm$ 0.16, significantly (p <0.05) lower than that of control group $(7.71 \pm 0.15)$. ACh-induced relaxation was significantly increased on losartan-treated group (p<0.01) at $10^{-6}$ M of ACh, and in captopril-treated group (p<0.05) at the range of $10^{-7}$ -$10^{-5}$ M of ACh. The $pD_{2}$ values for histamine-induced relaxatio of losartan, KR-30988 and captopril were 5.57 $\pm$ 0.10, 5.85 $\pm$ 0.21 and 5.60 $\pm$ 0.01, respectively, with significant differences in all groups (p<0.01) compared to that of control group (5.13 $\pm$ 0.09). ACh-induced relaxations of aortic preparations were not changed by pretreatment of indomethacin ($10_{-5}$ M), and completely bolcked by pretreatment of L-NAME $(10_{-5}M)$ in all groups. Sodium nitroprusside-induced relaxations were not significantly changed by all drugs tested in this experiments. These results suggest that $AT_{1}$ receptor antagonists, losartan and KR-30988, enhance the endothelium-dependent relaxatio on aortic preparations through the release of, or increase sensitivity, to nitric oxide in nor-motensive rats.

• 대한핵의학회지
• /
• 제38권6호
• /
• pp.498-505
• /
• 2004

목적: 신혈관성고혈압의 진단에서 캅토프릴 투여후 $^{99m}Tc$-DTPA 신기능곡선 및 신기능의 기준 별로 비교된 바 없다. 이 연구는 단측 신동맥협착에 의한 신혈관성고혈압에서 캅토프릴 스캔의 진단 기준별 성적을 비교함이었다. 대상 및 방법: 1995년 5월에서 2004년 5월까지 신혈관성고혈압이 의심되어 캡토프릴신장스캔과 신혈관조영술을 시행한 64명 중 신혈관협착 있어서(n=51), 혈관재성형술을 받은 37명 중 양측성 신혈관협착 13명을 제외한 24명을 대상으로 하였다. 동맥경화가 14예, 섬유근성이형성증이 4명, 기타 혈관염이 6명이었다. 캅토프릴 및 기저 스캔은 The Society of Nuclear Medicine의 표준화된 지침에 의하여, 신기능곡선(5등급) 및 상대적 신기능, 협착이 있는 신장의 캅토프릴과 기저 스캔의 신기능곡선의 등급차이(CBren), 신기능의 차이(BCfun) 및 캅토프릴스캔시 반대측 신기능곡선과의 등급 간의 차이(CNren) 를 구하였다. 결과: 24명(남/여=16/8, 나이 $39.2{\pm}18.4$세)중 8명이 완치, 11명이 호전되어 신혈관성고혈압으로 진단되었고, 5명이 혈압의 변화가 없었다. 신혈관성고혈압과 본태성고혈압군 간에 나이(median 30 vs. 52; p<0.05), 원인(동맥 경화/기타: 9/10 vs. 5/0, p<0.05), CBren (median 2.5 vs. 0; p<0.005), BCfun (median 4 vs -0.5; p<0.05), CNren (median 2 vs. 0; p<0.05)의 유의한 차이가 있었다. 성별, creatinine과 기저 및 캅토프릴시 신기능은 차이가 없었다. 수신자판단특성곡선하의 면적은 나이 0.826, CBren 0.929, BCfun 0.804, CNren 0.784로 곡선하의 면적은 유의한 차이가 없었다. 양성 및 음성예측도는 나이 38세 이하의 기준으로 100%(12/12), 42%(5/l2), BCfun 1% 이상 92%(11/12), 50%(3/6), CBren 1이상 92%(13/14), 75%(3/4), CNren 1이상 90% (17/19), 60% (3/5)였다. 유용한 진단기준으로 알려진 BCfun 5% 이상은 100%(4/4), 29%(4/14)였다. 결론: 캅토프릴스캔에서 신기능곡선과 신기능 모두 유용한 신혈관성고혈압의 기준이 되며, 신기능곡선은 기저스캔과의 비교없이도 정상 신장의 신기능곡선을 비교하여 신혈관성고혈압을 진단할 수 있다.