Combination Of Captopril Research Articles

The efficacy of captopril and 5-fluorouracil combination in the proliferation and collagen deposition of keloid fibroblast

Keloid is a benign fibroproliferative tissue growth that exceeds the initial wound margins. Captopril has been tested in vitro to reduce fibroblast proliferation and collagen deposition; thus, it has potential for use in the treatment of keloids. Meanwhile, 5‐fluorouracil (5‐FU) has already been used in keloid management. This study aimed to determine the efficacy of the combination of captopril and 5‐FU in keloid fibroblast cultures. Keloid tissues were cultured up to passages 4–7. The study consisted of a control group, captopril in various concentrations (10‐2, 10‐3, 10‐4, and 10‐5 mol/L), 5‐FU 1 mg/mL and a combination of captopril at various concentrations with 5‐FU 1 mg/mL. After 144 hours of treatment, fibroblast proliferation and collagen deposition were measured. The study showed a significant decrease in the mean index of fibroblast proliferation and collagen deposition in the group receiving captopril in various concentrations (10‐2, 10‐3, 10‐4, and 10‐5 mol/L) and the 5‐FU group against the control group (p<0.05). In the combined‐dose group, captopril at a concentration of 10‐2 mol/L and 5‐FU showed a significant reduction in fibroblast proliferation and collagen deposition compared to the 5‐FU group and the captopril at the same dose (p<0.05). In conclusion, the combination of captopril 10‐2 mol/L and 5‐FU 1 mg/mL is better at reducing fibroblast proliferation and collagen deposition in keloid fibroblast cultures than captopril or 5‐FU as a single therapeutic agent.

Consumption analysis of two-component fixed combinations of medicines for arterial hypertension treatment in Ukraine as one of the stages for evaluation of their reimbursement prospects

The aim was to conduct a retrospective consumption analysis of 4 groups of single pill combinations for hypertension treatment and identify potential candidates for future inclusion in the reimbursement list in Ukraine, based on retrospective consumption patterns.
 Materials and methods: The objects of the study were retail sales data in pharmaceutical market in Ukraine of four groups of single pill combinations used for arterial hypertension treatment. Data was provided by the marker research system “Pharmstandard” of the company of “Morion”. Analytic-comparative, systematic, logical, and mathematical-statistical methods were used.
 Results: Single pill combinations of ACE inhibitors with diuretics were the most consumed among other combinations on 2018-2020. Retrospective evaluation of consumption patterns in period of 2018-2020 showed that combinations of captopril and hydrochlorothiazide (HCTD) 50 mg/25 mg, enalapril and HCTD 10 mg/25 mg, lisinopril and HCTD 10 mg/12.5 mg were the most consumed. Among ARB and diuretics combinations valsartan and HTCD (160 mg/12.5 mg and 80 mg/12.5 mg) and losartan and HTCD (50 mg /12.5 mg) were the most consumed among ARB and diuretics combinations. Within ACE inhibitors and calcium channel blockers (CCB) combinations the most consumed were lisinopril/amlodipine 10 mg/5 mg and a perindopril arginine/amlodipine 5 mg/5 mg. Valsartan and amlodipine holds the majority among ARC and CCB combinations, consumed in period of 2018-2020.
 Conclusion: Apart from the single pill combinations, enlisted in the WHO Essential medicines list, eight more single pill combination were identified, based on retrospective consumption patterns, as potential candidates for further inclusion in the reimbursement list in Ukraine

Blockade of endothelial Mas receptor restores the vasomotor response to phenylephrine in human resistance arterioles pretreated with captopril and exposed to propofol

BackgroundHypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1–7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril.MethodsThe internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10–9 to 10–5 M) in the presence and absence of propofol (10–6 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10–5 M; added 30 min before phenylephrine) in separate experimental groups. Additional groups of arterioles were incubated for 16 to 20 h with captopril (10–2 M) or Ang 1–7 (10–9 M) before experimentation with phenylephrine, propofol, and A779.ResultsPropofol blunted phenylephrine-induced vasoconstriction in normal vessels. Captopril pretreatment alone did not affect vasoconstriction, but the addition of propofol markedly attenuated the vasomotor response to phenylephrine. A779 alone did not affect vasoconstriction in normal vessels, but it restored vasoreactivity in arterioles pretreated with captopril and exposed to propofol. Ang 1–7 reduced the vasoconstriction in response to phenylephrine. Addition of propofol to Ang 1–7-pretreated vessels further depressed phenylephrine-induced vasoconstriction to an equivalent degree as the combination of captopril and propofol, but A779 partially reversed this effect.ConclusionsMas receptor activation by Ang 1–7 contributes to phenylephrine-resistant vasodilation in resistance arterioles pretreated with captopril and exposed to propofol. These data suggest an alternative mechanism by which refractory hypotension may occur in anesthetized patients treated with ACE inhibitors.

Captopril and Spironolactone can Attenuate Diabetic Nephropathy in Wistar Rats by Targeting ABCA1 and microRNA-33.

Nephropathy diabetes is one of the important causes of death and a more prevalent cause of end-stage renal disease. The present study investigated the effect of applying spironolactone and captopril and their combination on some renal performance indices and cholesterol-efflux-related gene expression in nephropathy diabetic rats. Intraperitoneal injection of streptozotocin was used to induce diabetes in rats. FBS, creatinine, and BUN were assayed using the calorimetry technique; also, urine microalbumin was assayed by ELISA. Hepatic gene expressions of ABCA1, ABCG1, and miR-33 were evaluated by the real-time PCR method. FBS levels in the captopril-treated group were significantly decreased compared with the untreated diabetic group. BUN levels of treated groups with captopril and a combination of captopril + spironolactone were significantly increased. GFR of both treated diabetic groups with captopril and spironolactone was significantly lower than an untreated diabetic group. ABCA1 gene expression in hepatic cells of the combination of spironolactone + captopril treated group was significantly increased compared to other treated and untreated diabetic groups. The hepatic expression of the ABCG1 gene in the treated and untreated diabetic groups was significantly lower than in the control group. Treatment of the diabetic group with only combination therapy decreased the hepatic gene expression of miR-33 significantly. Obtained results suggest that S+C combination therapy can improve nephropathy and diabetes disorders by targeting the ABCA1 and miR-33 gene expression. It is suggested that miR-33 and ABCA1 genes evaluation could be a new therapeutic strategy for nephropathy diabetes remediation.

POSSIBILITIES OF PROLONGED BLOOD PRESSURE MONITORING IN ASSESSMENT OF THE EFFICACY AND SAFETY OF COMBINED ANTIHYPERTENSIVE THERAPY IN EMERGENCY CARE

<b>Introduction.</b> At the stage of emergency medical care, the time of observation of a patient receiving antihypertensive therapy is limited to the time of stay of the emergency medical service team with this patient. Therefore, assessing the efficacy and safety of prescribing a particular antihypertensive treatment pattern is a relevant task. <br><b>Patients and Methods.</b> In this study, we used three two-component combinations of antihypertensive drugs (captopril and furosemide, moxonidine and furosemide, moxonidine and nifedipine) and prolonged blood pressure monitoring. We included 105 patients with a history of primary arterial hypertension who called an ambulance because of an increase in blood pressure and signed a voluntary informed consent. Evaluation of the results of prolonged blood pressure monitoring was carried out in 91 patients. The comorbidity, the clinical condition of the patient, blood pressure monitoring parameters, the efficacy and safety of antihypertensive therapy at the prehospital stage were evaluated. <br><b>Results.</b> The most pronounced and somewhat excessive hypotensive effect developed when using a combination of moxonidine with nifedipine. The index of excessive decrease in blood pressure below 120/70 mm Hg in this group was 51.6% (p<0.05), as compared to the combinations of captopril with furosemide and moxonidine with furosemide (10.3% and 7.8%, respectively). <br><b>Conclusion.</b> The use of blood pressure monitoring in patients with a clinically significant increase in blood pressure on prehospital stage allows us to assess the dynamics of blood pressure, the effectiveness and safety of prescribing various combinations of antihypertensive drugs.

Combination of Captopril with Gliclazide Decreases Vascular and Renal Complications and Improves Glycemic Control in Rats with Streptozotocin- Induced Diabetes Mellitus.

The common antihypertensive angiotensin-converting enzyme (ACE) inhibitor captopril was reported to possess anti-oxidant and anti-inflammatory effects in different experimental models. Diabetic vascular complications arise from increased vascular endothelial inflammation and oxidative stress as well as decreased nitric oxide bioavailability in the vessel walls due to poor glycemic control. This study aimed to evaluate the role of captopril and gliclazide in decreasing diabetes mellitus (DM) vascular complications caused by decreased cellular glucose uptake and impaired endothelial nitric oxide metabolism, as well as examine the effects of the combination on diabetic renal complication and plasma lipid profile. Adult male Wister rats received captopril (25 mg/kg/day) and/or gliclazide (10 mg/kg/- day) by oral gavage daily for one month after induction of DM using streptozotocin (50 mg/kg, i.p., once). Serum glucose and insulin levels, inflammatory mediators like TNF-α, oxidative stress biomarkers like glutathione and nitric oxide, and plasma lipid profile were measured. Besides, histopathological examination of the thoracic aorta and kidney tissues, Western blot assessed the expression of nitric oxide synthase (NOS) subtypes in the thoracic aorta. Captopril significantly improved vascular architecture and oxidative stress and modulated nitric oxide synthesis via regulation of nitric oxide synthases, as well as decreased inflammation via down-regulating TNF-α, decreased systolic and diastolic blood pressure, and improved serum lipid profile in diabetic rats. Gliclazide increased serum insulin and decreased serum glucose, as well as its anti-oxidant and anti-inflammatory effects. Captopril showed a promising protective effect against DM vascular complications, at least via nitric oxide modulating effect, anti-oxidant effect, and anti-inflammatory activity that appeared in biochemical and histopathological findings, lipid profile, renal function, and architecture improvements. Combining gliclazide with captopril gives an additive effect through enhanced glycemic control and increased anti-oxidant and anti-inflammatory properties above captopril alone.

Kidney protective effect of acalypha indica linn. root extract in high-fructose and high-cholesterol diet-fed rats

Diet high in fructose and cholesterol may lead to the development of diabetic nephropathy (DN). One of the first drugs of choice in DN treatment is captopril. Prolonged use of this drug may lead to some adverse effects and the treatment can be optimized through using other therapy options. Acalypha indica Linn. (AI) may be an alternative herbal therapy for DN. The objective of this research is to investigate the renoprotective effect of AI on DN. For seven weeks, thirty-two Sprague-Dawley rats were divided into groups receiving normal diet and high-fructose and high-cholesterol diet (HFCD). Then, the HFCD-fed rats were divided into four groups receiving different treatment: negative control, AI root extract (250 mg/kgBW), captopril (2.5 mg/kgBW), and combination of captopril and AI. Normal diet group was divided into AI and no treatment. After four weeks of treatment, the rats were terminated and serum urea and creatinine levels were measured. In the normal group, AI therapy decreased serum urea and creatinine levels. In the HFCD groups, AI and captopril monotherapy groups had increased serum urea levels, but lower compared to negative control. Meanwhile, serum creatinine levels decreased in both groups. However, these findings are not statistically significant. We found that combination therapy group had the highest increase in serum urea level, which was significantly different with captopril group (p=0.01). Serum creatinine level was also increased in this group. Our present study showed that AI tend to reduce serum urea and creatinine levels in normal diet group and inhibit the increase of serum urea and creatinine levels in rats fed with HFCD diet. Antagonistic interaction between captopril and AI might be present.

Kajian Penggunaan Antihipertensi dan Potensi Interaksi Obat Pada Pengobatan Pasien Hipertensi Dengan Komplikasi

Hipertensi secara luas dikenal sebagai penyakit kardiovaskular dan merupakan salah satu faktor risiko penyebab terjadi gagal ginjal kronik (GGK). Penderita hipertensi dengan gangguan ginjal menempati posisi dengan angka kejadian terbesar (35%) dibandingkan dengan hipertensi yang menyebabkan komplikasi pada organ lain. GGK merupakan suatu keadaan klinik yang ditandai dengan penurunan fungsi ginjal yang ireversibel. Pemberian obat antihipertensi lebih dari satu dapat menimbulkan interaksi obat (Fitriani, 2007). Penelitian Rahmawati et al. (2006) tentang kajian retrospektif interaksi obat di RS pendidikan dr. Sardjito Yogyakarta melaporkan bahwa interaksi obat yang terjadi pada pasien rawat inap sebesar 59%. Untuk pasien rawat inap ditemukan 125 kejadian interaksi obat. Interaksi obat antihipertensi yang paling banyak terjadi adalah kombinasi kaptopril dan furosemidTujuan dari penelitian ini adalah untuk mengetahui gambaran pengobatan antihipertensi pada pasien hipertensi dengan GGK beserta kerasionalan terapi ditinjau dari aspek tepat indikasi, tepat pasien, tepat dosis dan tepat obat berdasarkan JNC VIII. Dan penelitian yang lain bertujuan untuk meneliti potensi interaksi obat pada terapi antihipertensi.
 Metode penelitian yang digunakan adalah jenis penelitian deskriptif yang bersifat non-eksperimental, data yang diambil secara retrospektif. Sampel penelitian ini adalah pasien yang terdiagnosis hipertensi dengan komplikasi yang mendapatkan terapi kombinasi antihipertensi yang memenuhi kriteria inklusi dan eksklusi. 
 Hasil penelitian pertama menunjukkan bahwa obat antihipertensi yang paling banyak digunakan oleh pasien adalah golongan diuretik loop yaitu furosemid (9,23%). Kategori ketepatan obat menurut JNC VIII didapatkan untuk terapi indikasi (100%), tepat pasien (100%), tepat obat (78,5%) tepat dosis (98,46%). Hasil penelitian kedua menunjukan terdapat 31 pasien (81,58%) yang mengalami interaksi obat dan 7 pasien (18,42%) tidak mengalami interaksi obat. Dari total 31 pasien potensi interaksi yang paling banyak terjadi adalah moderate 120 (53,6%). Obat yang paling banyak digunakan dan menimbulkan interaksi adalah catapres dengan diazepam menimbulkan interaksi moderate.

Combination treatment of captopril and prazosin to treat patients with gestational hypertension

Gestational hypertensive disorder is a complication of pregnancy, which adversely affects mother-child health. Captopril and prazosin are two agents that are frequently applied for the treatment of patients with gestational hypertension. However, the cooperative efficacy of captopril and prazosin has been not investigated in a previous study. In the present study, the comprehensive treatment of captopril and prazosin for the treatment of patients with gestational hypertension was investigated. A total of 324 patients with gestational hypertension were recruited to analyze the therapeutic effects of captopril and prazosin in patients with gestational hypertension. The duration of the treatment, dose-limiting toxicities and maximum tolerated dose of captopril and prazosin were examined in this cohort. Furthermore, the levels of blood pressure and proteinuria were also examined in patients with gestational hypertension who received treatment with captopril and/or prazosin with placebo as a control. Serum levels of vasodilation-converting enzyme and α-adrenergic receptor were also examined prior to and during the 4-week post-treatment period. It was observed that the most common treatment-emergence adverse events were hypertension and proteinuria following 4-week treatments. The data revealed that captopril or prazosin treatments significantly ameliorated gestational hypertension and symptoms compared with placebo (P<0.01). Notably, the combination of captopril and prazosin treatments significantly ameliorated hypertension and proteinuria and reduced the expression levels of vasodilation-converting enzyme and α-adrenergic receptor (all P<0.01), which contributed to beneficial effects on complications and blood coagulation mechanism compared with either captopril or prazosin treatment. In conclusion, the present clinical study indicated that combination treatment of captopril and prazosin exhibited more efficient outcomes than the single agent by improving gestational hypertension, indicating that a comprehensive therapeutic regimen of captopril and prazosin may be a potential clinical opinion for patients with gestational hypertension.

Protective effect of captopril on cardiac fibrosis in diabetic albino rats: a histological and immunohistochemical study

Background Cardiomyopathy is one of the common complications of diabetes mellitus.Aim The aim of the present study was to investigate the effects of Captopril on myocardial fibrosis in streptozotocin-induced diabetic rats (an animal model of type 1 diabetes mellitus).Materials and methods Forty albino rats were divided into five groups. Group I (control group), group II (untreated diabetic rats), group III (insulin-treated diabetic rats), group IV (Captopril-treated diabetic rats), and group V (insulin and Captopril-treated diabetic rats) were killed at 4 and 8 weeks, and the samples were collected for histological evaluation using hematoxylin and eosin, Masson trichrome, and immunohistochemical staining with anti-P53 for apoptosis, alpha smooth muscle actin (α-SMA) for collagen deposition.Results Treatment of streptozotocin-induced diabetic rats with insulin and Captopril (group V) showed marked decrease in myocardial injury and apoptosis, which was confirmed by marked decrease of sarcoplasmic p53 expression. Group V also showed decreased collagen deposition as confirmed by Masson trichrome staining and α-SMA expression. The results were better after 8 weeks compared with those after 4 weeks.Conclusion The administration of Captopril alone with diabetic rats minimally affected cardiac fibrosis, while the combination of Captopril and insulin markedly improved cardiac fibrosis.

Pentoxifylline treatment enhances antihypertensive activity of captopril through hemorheological improvement in spontaneously hypertensive rats during development of arterial hypertension

The rheological properties of blood play a significant role in the onset and progression of arterial hypertension. The aim of our work was to evaluate the effect of the angiotensin-converting enzyme inhibitor captopril (20 mg/kg/d), pentoxifylline (PTX; 100 mg/kg/d), and the combination of captopril + PTX (20 + 100 mg/kg/d) on the hemodynamic and hemorheological parameters in spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. In the group of animals that received captopril, the mean arterial pressure (MAP) was significantly lower by 30% due to a decrease in cardiac output of 23% and in total peripheral resistance (TPR) of 26% compared with the control group, whereas blood viscosity did not change significantly. PTX-treated SHRs had significantly lower MAP and TPR (by 19% and 31%, respectively) and blood viscosity (by 4%–6%) and a higher erythrocyte deformability index (by 1.5%–2%) than the control group. In the group of animals that received captopril + PTX, MAP and TPR were significantly lower, by 41% and 46%, than those in the control group, and by 16% and 27% than those in the captopril group. The combination of the angiotensin-converting enzyme inhibitor captopril and the hemorheological agent PTX, affecting various systems that are involved in blood pressure regulation, exhibits synergism and prevents an increase in arterial blood pressure during the development of arterial hypertension in SHRs (ie, from 5 to 11 weeks of life).

A Clinical Experience on Sulodexide in the Treatment of Patients with Diabetic Nephropathy

Background: Diabetic nephropathy, characterized by albuminuria, is a severe complication of diabetes mellitus, leading cause of end-stage renal disease. The aim of the present study was to evaluate the efficacy and safety of sulodexide, alone or in combination with captopril, versus captopril alone in consecutive adult patients with diabetic nephropathy. Methods: Patients aged ≥ 18 years, with type 1 or type 2 diabetes mellitus and albumin excretion rate (AER) ≥ 30 mg/24 h, without severe renal insufficiency, cardiac or hepatic insufficiency, or haematuria, were enrolled. Patients were treated with captopril 25 mg twice daily, sulodexide 25 mg twice daily, or a combination of captopril 25 mg twice daily + sulodexide 25 mg twice daily for 6 months. The primary endpoint was the evaluation of AER. Secondary endpoints included evaluation of arterial blood pressure, fasting glucose, HbA1c, serum creatinine and uricemia and safety. Results: Globally, 123 patients were enrolled and treated with captopril alone (n=42), sulodexide alone (n=53) or sulodexide plus captopril (n=28). After adjustment for initial albuminuria, the AER reduction at T3 and T6 versus T0, although highly significant in all treatment groups, was higher in patients treated with the combination or with sulodexide alone than in patients given captopril alone (further decrease of 17.6% and 18.2% at T3 and of 29.3% and 19.8% at T6, respectively). In the whole population, serum creatinine and uric acid levels increased during the study, HbA1c and fasting glucose levels increased from T0 to T3 and remained stable thereafter, while blood pressure was constant throughout the study. Sulodexide was well tolerated. Conclusions: Long term administration of sulodexide 50 mg/day, both in monotherapy or in combination with captopril, is effective and well tolerated in reducing proteinuria in diabetic patients and can be considered a valid therapeutical option in order to prevent major complications and reduce morbidity and mortality in this population.

Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria.

Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored. In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P<0.05) with nonsignificant differences in membrane fluidity. Decrease in the value of maximum reaction rate Vmax (P<0.05) without any change in the value of Michaelis-Menten constant Km, indicative of a noncompetitive inhibition, was presented. At the in vivo level, we did not demonstrate any significant changes in the ATP synthase activity and the membrane fluidity in rats receiving captopril, nifedipine, and combined therapy. In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria.

Epoxyeicosatrienoic Acid Analog Reduces Proteinuria And Renal Cast Formation In Experimental Radiation Nephropathy

Thirty‐three million Americans are estimated to have chronic kidney disease (CKD). Exposure to radiation through industrial accidents, terrorist events, or total body irradiation (TBI) associated with hematopoietic stem cell transplant (HSCT), increases the risk for acquiring CKD. Clinical symptoms of human radiation nephropathy (i.e. azotemia, hypertension, proteinuria, anemia) can present within 6–12 months following irradiation in cases of acute radiation exposure. Current therapies for radiation nephropathy are limited and variable in their success. Our laboratory has demonstrated that epoxygenase metabolites of arachidonic acids epoxyeicosatrienoic acids (EETs) protect the kidney in different pathologies. We have developed novel small molecule EET analogs that protect from cisplatin‐induced and hypertension‐induced kidney injury. The aim of this research study is to examine the efficacy of a novel therapeutic, EET‐A, in reducing kidney damage following total body TBI (11 Gy) in WAG/RijCmcr rats. We also examined the efficacy of the current therapy, captopril (an ACE inhibitor) to treat experimental radiation nephropathy when administered alone or in combination with EET‐A. Four groups (n=6/group) of male WAG/RijCmr rats received TBI and were treated with vehicle (TBI‐V), EET‐A (10mg/kg/d p.o.; TBI‐EET‐A), captopril (15mg/kg/d p.o.; TBI‐Cap), or the combination of captopril and EET‐A (TBI‐Cap, 15mg/kg/d + EET‐A, 10mg/kg/d). Treatment was started when the rats developed azotemia (BUN 30–50 mg/dL) and was continued for 45 days. Renal tissue and urine samples were collected from the rats at the end of the treatment period. Treatments were simultaneously compared in their effectiveness of reducing the effects of radiation nephropathy‐associated proteinuria in rats through analyses of protein‐to‐creatinine ratios, and percent quantification of protein casts within medulla and cortex histological cross‐sections. TBI‐V rats were markedly proteinuric with protein‐creatinine ratio of 59±6 mg/mg. All treatments reduced proteinuria by 20–55% and a one‐way ANOVA demonstrated that overall differences in the protein/creatinine ratio existed between drug treatments, F (5,38)=8.126; p&lt;0.05. Pairwise comparisons between the TBI‐Cap (32.5±5 mg/mg) and TBI‐Cap+EET‐A (30.1±3 mg/mg) revealed no statistical difference (p&gt;0.05). All treatments reduced protenaceous tubular cast formation in TBI rats. TBI‐EET‐A, TBI‐Cap, and TBI‐Cap+EET‐A groups demonstrated a comparable effect in reducing cortical tubular cast formation with ~75% reduction. On the other hand, TBI‐Cap (70%) and TBI‐Cap+EET‐A (86%) treatments were more effective than TBI‐EET‐A (50%) in reducing medullary protein casts. Overall, captopril and its combination with EET‐A were comparatively more effective than EET‐A alone in reducing medullary cast formation. Our data demonstrates that EET‐A or EET‐A in combination with captopril can be effective treatments for radiation nephropathy.

Hypertension Treatment and Control in Older Adult at Tanjung Sari Primary Health Care

Background : Hypertension is considered as a major health problem in Indonesia, especially in older adult population because of its prevalence increases by age. Treatment strategy and control management of hypertension in Public Health Center (Pusat Kesehatan Masyarakat, Puskesmas) as primary health care should be enhanced to overcome this issue. This study aimed to describe the pattern of antihypertensive agent in older adults. Methods : This was a descriptive study with total sampling method for data collection. Data were collected from medical record of older adult patients with diagnosis of hypertension at Puskesmas Tanjung Sari from January to December 2013. The variables observed were gender, number of visits, the degree of hypertension, types of antihypertensive drug, combinations of antihypertensive drugs, and blood pressure control. Results : The number of older adults with hypertension was 180 people. Some of which, 120 women (66.7%) participated, 152 (84.4%) had hypertension stage 2, 100 (55.6%) had just one visit, and 80 (44.4%) had more than one visit. Among 80 participants with more than one visit, 8 had achieved target blood pressure. There were 166 participants (92.2%) who received single antihypertensive agent (captopril was given the most), and 14 participants (7.8%) who received the combination of two antihypertensive agent (combination of captopril and HCT (hydrochlorothiazide)) were given the most). Conclusions : More than 75% of older adult with hypertension have stage 2 hypertension and are treated by single antihypertensive agent. Ninety percent of the patient have uncontrolled blood pressure. [AMJ.2016;3(1):17–21] DOI: 10.15850/amj.v3n1.699

Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans.

Background. Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.

Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

EFFICACY OF CAPTOPRIL, MOXONIDINE AND THEIR COMBINATIONS WITH NIFEDIPINE IN THE NON-THREATENING HYPERTENSION

Objective. To study several medications and their combinations in non-threatened hypertension worsening captopril, and moxonidine, captopril + nifedipine, captopril + moxonidine.Design and methods. We include326 patients (253 females) aged 45–89 years who referred for the urgent health care due to the non-threatene hypertension worsening. Mean duration of hypertension was 20,6 ± 0,6 years. Special questionnaires were fille in, heart rate, blood pressure by Korotkoff method, and electrocardiogram were registered.Results. Moxonidinwas shown to be more effective in patients with the sympathetic hyperactivity, captopril — in patients withouincreased sympathetic activity. The combination of captopril and nifedipine was associated with the reductioof therapy effi ciency, and the combination of moxonidine and nifedipine — with its increase. Moreover, administration of captopril and nifedipine led to the higher rate of side effects, compared to the combination moxonidine and nifedipin.

Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1–50 mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5–10 mg/kg) and INV-161 (1–10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.

Deletion of the Distal C Terminus of CaV1.2 Channels Leads to Loss of β-Adrenergic Regulation and Heart Failure in Vivo

L-type calcium currents conducted by CaV1.2 channels initiate excitation-contraction coupling in cardiac and vascular smooth muscle. In the heart, the distal portion of the C terminus (DCT) is proteolytically processed in vivo and serves as a noncovalently associated autoinhibitor of CaV1.2 channel activity. This autoinhibitory complex, with A-kinase anchoring protein-15 (AKAP15) bound to the DCT, is hypothesized to serve as the substrate for β-adrenergic regulation in the fight-or-flight response. Mice expressing CaV1.2 channels with the distal C terminus deleted (DCT-/-) develop cardiac hypertrophy and die prematurely after E15. Cardiac hypertrophy and survival rate were improved by drug treatments that reduce peripheral vascular resistance and hypertension, consistent with the hypothesis that CaV1.2 hyperactivity in vascular smooth muscle causes hypertension, hypertrophy, and premature death. However, in contrast to expectation, L-type Ca2+ currents in cardiac myocytes from DCT-/- mice were dramatically reduced due to decreased cell-surface expression of CaV1.2 protein, and the voltage dependence of activation and the kinetics of inactivation were altered. CaV1.2 channels in DCT-/- myocytes fail to respond to activation of adenylyl cyclase by forskolin, and the localized expression of AKAP15 is reduced. Therefore, we conclude that the DCT of CaV1.2 channels is required in vivo for normal vascular regulation, cell-surface expression of CaV1.2 channels in cardiac myocytes, and β-adrenergic stimulation of L-type Ca2+ currents in the heart.