• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.237-244
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• 1993

The effect of nicotine on the secretion of $[Met^{5}]-enkephalin$ (ME) in addition to proenkephalin A (proENK) mRNA levels and effects of indomethacin, nordihydroguaiaretic acid (NDGA), and captopril on nicotine-induced responses were studied in bovine adrenal medullary chromaffrin (BAMC) cells. Long-term exposure of BAMC cells to nicotine at a concentration of $10{\mu}M$ significantly increased proENK mRNA level and the secretion of ME into the medium. Treatment of BAMC cells with NDGA (a lipoxygenase inhibitor, $10{\mu}M$), indomethacin (a cycloooxygenase inhibitor) or captopril (an angiotensin converting enzyme inhibitor) alone did not affect ME secretion and proENK mRNA levels. The pretreatment of BAMC cells with NDGA inhibited the increased ME secretion and proENK mRNA level induced by nicotine. However, indomethacin and captopril did not affect nicotine-induced responses. Our results indicate that neuronal regulations of ME secretion and proENK mRNA level induced by nicotine in BAMC cells are in part mediated by a lipoxygenase-but not cyclooxygenase-and endogenous renin-angiotensin pathway.

• Journal of Veterinary Science
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• v.24 no.2
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• pp.26.1-26.11
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• 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
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• v.34 no.3
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• pp.223-229
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• 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
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• v.14 no.2
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• pp.474-482
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• 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
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• v.28 no.1
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• pp.7-13
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• 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.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.312-317
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• 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.

• The Korean Journal of Nuclear Medicine
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• v.24 no.2
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• pp.325-331
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• 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
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• v.19 no.5
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• pp.390-395
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• 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.

• The Korean Journal of Nuclear Medicine
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• v.38 no.6
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• pp.498-505
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• 2004

Purpose: We compared captopril renal scintigraphic criteria for the diagnosis of renovascular hypertension by unilateral renal artery stenosis. Materials and Methods: The study group consisted of 24 patients (m/f : 16/8, age: $39{\pm}18$ years) with unilateral renal artery stenosis who underwent renal artery revascularization and captopril renal scintigraphy with $^{99m}Tc$-diethylenetriaminepentaacetic acid between May 1995 and April 2004. The blood pressure response was classified as cure/improvement or failure. We evaluated captopril-induced changes in relative function (BCfun) and renogram grade (0 to 5: 0=normal, and 5=renal failure pattern without measurable uptake) (CBren) and the difference of renograms between the normal and stenotic kidney on captopril scan (CNren). Results: light of 24 patients were cured and 11 improved and 5 patients were classified as failed revascularization. Significant predictors of a cure or improvement of blood pressure were younger age, stenosis by fibromuscular dysplasia or arteritis, BCfun, CBren and CNren. Areas under the receiver operating characteristic curve of age, BCfun, CBren and CNren were not significantly different. Positive and negative predictive values of predictors were 100% and 42% (age ${\leq}38$): 92% and 50% (BCfun ${\geq}1%$): 92% and 75% (CBren ${\geq}1$), and 90% and 60% (CNren ${\geq}1$), respectively. Conclusion: Captopril induced changes in renal function and renogram can reliably predict hypertension response to revascularization. Renogram pattern on captopril scan can diagnose renovascular hypertension without baseline data in patients with unilateral renal artery stenosis.