Captopril: Evaluation of Low Doses, Twice-Daily Doses and the Addition of Diuretic for the Treatment of Mild to Moderate Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 443s-445s ◽  
Author(s):  
◽  
Barry J. Materson
Keyword(s):  
Blood Pressure ◽  
Adverse Effects ◽  
Diastolic Blood Pressure ◽  
Low Dose ◽  
Moderate Hypertension ◽  
Treated Group ◽  
Daily Treatment ◽  
High Dose ◽  
Low Doses

1. We randomized 475 men whose diastolic blood pressure was 92–109 mmHg to either placebo- or captopril-treated (37.5, 75 and 150 mg/day) groups for 7 weeks. 2. After 7 weeks, the placebo-treated patients were given hydrochlorothiazide (25 mg twice daily), as were two-thirds of each captopril-treated group, and they were observed for 7 additional weeks. 3. Captopril reduced blood pressure by 12.2 ± 0.8/9.4 ± 0.4 mmHg at 7 weeks (n = 323) and captopril plus placebo by 10.3 ± 1.9/10.2 ± 0.9 at 14 weeks (n = 83); placebo by 20 ± 1.7/3.4 ± 0.8 (n = 76); captopril plus hydrochlorothiazide by 24.4 ± 1.1/16.2 ± 0.6 (n = 173). The effect of low-dose captopril was similar to that of a high dose. The effect of twice-daily captopril appeared to be equal to that of thrice-daily treatment but monitoring studies are needed to confirm this. 4. Only 15 out of 384 (3.9%) of patients were dropped from the study because of adverse effects. 5. Low-dose captopril may be useful in patients with mild to moderate hypertension.

scholarly journals Comparison between methyldopa and combination of methyldopa and nifedipine in terms of mean change in blood pressure in pregnancy induced hypertension

2021 ◽  
Vol 15 (7) ◽  
pp. 1703-1705
Author(s):  
Bilqees Akhtar Malik ◽  
Shahzad Bashir Momina ◽  
Tazeen Ashraf
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Gestational Age ◽  
Low Dose ◽  
High Dose ◽  
Pregnancy Induced Hypertension ◽  
Induced Hypertension ◽  
Group A ◽  
Group B ◽  
In Pregnancy

Objective: Comparison between Methyldopa and combination of Methyldopa and Nifedipine in terms of mean change in blood pressure in pregnancy induced hypertension. Material and methods: This randomized controlled trial was conducted at Department of Obstetrics and Gynecology, Combined Military Hospital Bahawalpur from February 2020 to August 2020 over the period of 6 months. Total 80 patients with pregnancy induced hypertension as per operational definition having age 20-40 years and having gestational age ≥ 20 weeks assessed on LMP were selected. Results: Mean age of the patients was 30.81 ± 5.670 years, mean age of patients of group A was 31.50 ± 5.809 years and mean age of group B was 30.13 ± 5.515 years. Mean gestational age was 30.17 ± 5.981 weeks, mean gestational age of patients of group A was 29.70 ± 6.329 weeks and mean gestational age of patients of group B was 30.65 ± 5.65 weeks. In group A, mean diastolic blood pressure was decrease from 101.2250 ± 4.97938 to 84.5000 ± 3.26599 and in group B from 107.7750 ± 7.18434 to 82.5000 ± 2.25320. Comparison of mean decrease in diastolic blood pressure between group A (High dose Methyldopa) and group B (Low dose Low dose Methyldopa with Nifedipine) was done. Mean decrease in diastolic blood pressure in group A was 16.72 ± 3.935 and in group B was 25.28 ± 6.876. Statistically significant difference of mean decrease in diastolic blood pressure between the both groups was noted with p value 0.000. Conclusion: Results of this study showed that Low dose Methyldopa with Nifedipine combination is more effective as compared to High dose Methyldopa to reduce diastolic blood pressure in pregnant women suffering from pregnancy induced hypertension. Keywords: Diastolic blood pressure, Methyldopa, Nifedipine, Pregnancy induced hypertension, Systolic blood pressure

scholarly journals Ripk3 Signaling Regulates Hematopoietic Stem Cell Number and Function during Stress

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3714-3714
Author(s):  
Lei Zhang ◽  
Huacheng Luo ◽  
Jing Li ◽  
Hong-Min Ni ◽  
Mark Sellin ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Low Doses ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Leukemia Development ◽  
Serial Transplantation

Background: Among all tissues, bone marrow (BM) is the most sensitive tissue to ionizing radiation (IR)-induced acute tissue damage (ATD) and chronic long-term residual damage (LT-RD). BM failure and a significant reduction in blood cells (pancytopenia) often occurs within days after exposure to IR due to the massive death of proliferative hematopoietic progenitor cells (HPCs). However, due to their quiescent cell cycle status and reduced fidelity of DNA repair feature, many hematopoietic stem cells (HSCs) cannot fully eliminate such damage and enter senescence; this results in LT-RD. Abnormal dysplastic hematopoiesis is the most common LT-RD in most victims of IR, followed by an increased risk of leukemia/lymphoma development. Thus IR exposure is an established cause of BM failure and leukemia. A significant increase in the production of inflammatory cytokines is induced by IR which contributes to the pathogenesis of both ATD and LT-RD. Such inflammatory cytokines induce the activation of Ripk3-Mlkl-mediated necroptotic signaling in HSCs. However, the role of Ripk3-Mlkl signaling in IR-induced damage has not studied. Experimental procedures: The self-renewal capacity of HSCs among Ripk3-/-, Mlkl-/- and WT mice were examined and compared by serial transplantation assay. The phenotypes of ATD and LT-RD induced by different dosages of IR were compared among Ripk3-/-, Mlkl-/- and WT mice. The mechanism by which Ripk3 signaling prevents IR-induced leukemia development was studied. Results: Ripk3-Mlkl signaling is not required for hematopoiesis during homeostatic condition. However, during serial transplantation, inactivation of such signaling prevents stress-induced loss of HSCs. Interestingly, Ripk3 signaling also induces an Mlkl-independent ROS-p38-p16-mediated senescence in HSCs. Thus Ripk3-/- HSCs showed better competitive hematopoietic ability compared to Mlkl-/- and WT HSCs during serial transplantation. A sub-lethal dosage of IR (6Gy) induces Ripk3-dependent NF-κB activation and pro-survival gene expression in HSCs, which is necessary for the survival of damaged HSCs. After 6Gy IR, although DNA damage is repaired in most HSCs within 2 days, a proportion of HSCs in WT and Mlkl-/- mice fail to fully repair the damage and undergo p53-p21-dependent senescence. However such cells in Ripk3-/- mice die from apoptosis. Thus the remaining HSCs in Ripk3-/- mice should be functionally normal, while a proportion of the remaining HSCs in Mlkl-/- and WT mice remain damaged but senescent, all as demonstrated by competitive hematopoietic reconstitution assay. Multiple low-doses of IR (1.75Gy once week × 4) induce HSC exhaustion in WT mice but not in Ripk3-/- and Mlkl-/- mice. Interestingly, almost all Ripk3-/- mice develop acute lymphoblastic leukemia within 200 days after such low dose IR, while 45% of WT and 60% of Mlkl-/- mice develop thymomas within 360 days (see Figure). Mechanistically, such low-dose IR stimulates chronic inflammatory cytokine production. Such cytokines induce Ripk3-Mlkl-mediated necroptosis in response to HSC exhaustion observed in WT mice. These cytokines also induce Ripk3-ROS-p38-p16-mediated senescence in response to impaired HSC functioning observed in both WT and Mlkl-/- mice. In Ripk3-/- mice, due to the lack of both necroptotic and senescent signaling, mutant HSCs accumulate and leukemia development is accelerated. Conclusion: Ripk3 signaling plays distinct roles in HSCs in response to different doses of IR. High-dose IR induces Ripk3-dependent NF-κB/survival signaling, which is required for the survival of HSCs which fail to repair the damage. Thus temporal inhibition of Ripk3-NF-κB signaling might help to remove the damaged HSCs thus preventing the occurrence of LT-RD. However multiple low-doses of IR induces Ripk3 activation in HSCs which represses leukemia development by inducing both ROS-p38-p16-mediated senescence and Ripk3-Mlkl-mediated necroptosis. Induced activation of Mlkl-necroptosis might help to repress leukemia development by removing damaged HSCs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Marwa M. M. Refaie ◽  
Entesar F. Amin ◽  
Nashwa F. El-Tahawy ◽  
Aly M. Abdelrahman
Keyword(s):  
Protective Effect ◽  
Low Dose ◽  
Caspase 3 ◽  
Interleukin 1 ◽  
Treated Group ◽  
Limiting Factors ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.

Abstract P242: Nicotinic Acetylcholine Receptor Subunit α7 is Protective Against Angiotensin II-induced Aneurysm and Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Nayaab S Khan ◽  
Spyros Mavropoulos ◽  
Kaie Ojamaa
Keyword(s):  
Blood Pressure ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Low Dose ◽  
Histological Analysis ◽  
Inflammatory Activity ◽  
High Dose ◽  
Ang Ii ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr

Alpha7 nicotinic acetylcholine receptor (α7 nAChR), an integral component of the cholinergic nervous system is known to mediate cholinergic anti-inflammatory activity in various disease models such as sepsis, stroke and neurocognitive disorders. We report for the first time that the α7 nAChR -/- deficient mouse serves as a novel model of hypertension and aneurysm formation. Seven month old male WT and α7 nAChR -/- mice weighing 28-33g were infused with low dose Ang II (350 ng/kg/min) or high dose (700 ng/kg/min) or vehicle for 15 days using mini-osmotic pumps (Alzet, model 2004) implanted subcutaneously. Blood pressure (BP) was recorded on day 0,3,7,10 and 14. Mice were euthanized on day 15. Heart and body weights were measured, histological analysis was performed on the aortas and immune profile of peripheral blood was analyzed by flow cytometry. High dose Ang II resulted in 70% mortality from aneurysm rupture in α7 nAChR -/- mice starting as early as the 4 th day of infusion. While cardiac hypertrophy was not observed, low dose Ang II resulted in a sharp rise in blood pressure in α7 nAChR -/- beginning on the 3 rd day to 167±3.7 mmHg compared to 138±3.3 mmHg in WT treated mice. On day14 of low dose treatment, BP in α7 nAChR -/- rose to 171±4.2 vs.135±3.1 in WT mice. No changes were observed in BP of untreated WT or α7 nAChR -/- animals. Histological analysis revealed high grade aneurysm in aortas of α7 nAChR -/- mice treated with low dose Ang II, demonstrating a prominent germinal center within the false lumen and fibrous desmoplastic stroma. Increased infiltration of CD11B + monocytes, and myeloperoxidase + stained neutrophils were observed in these aortas but not in the aortas of similarly treated WT mice. Flow cytometric analysis showed 27% ± 3.9 CD11B + /CD45 + circulating monocytes and 48% ± 0.8 Ly6G + /CD45 + neutrophils in α7 nAChR -/- vs. 19% ± 3 monocytes and 11.85% ± 2.9 neutrophils in WT mice. No differences in the levels of circulating immune cells were observed in untreated mice of either genotype. These data support a protective role of α7 nAChR in hypertension and aneurysm, potentially acting through its cholinergic anti-inflammatory activity. The α7 nAChR -/- mouse may serve as a new genetic model of aneurysm relevant in studies of the human disease.

Abstract 528: Dose- And Salt-dependency Of Angiogenesis Inhibition-induced Blood Pressure Rise And Renal Toxicity

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Stephanie Lankhorst ◽  
Mariëtte H Kappers ◽  
Stefan Sleijfer ◽  
A H Danser ◽  
Anton H van den Meiracker
Keyword(s):  
Low Dose ◽  
Renal Toxicity ◽  
Pressure Rise ◽  
High Salt ◽  
High Dose ◽  
Low Doses ◽  
High Salt Diet ◽  
Salt Diet ◽  
Angiogenesis Inhibition ◽  
Cystatine C

Angiogenesis inhibition with the VEGF inhibitor sunitinib is an established anti-cancer therapy, inducing hypertension and nephrotoxicity. We explored the dose- and salt-dependency of these side effects. In male WKY rats, mean arterial pressure (MAP) was monitored telemetrically during oral treatment with a high (27.5 mg/kg.day, n=14), an intermediate (14 mg/kg.day, n=6) and low dose (7 mg/kg.day, n=6) of sunitinib or vehicle (n=8) after normal salt diet for 2 weeks. The low dose-model was also combined with a high salt diet (8% NaCl and saline water). Eight days after administration rats were sacrificed and blood and 24h urine samples collected for biochemical measurements. With the high dose of sunitinib, MAP increased from 94.7±0.9 mmHg to 125.8±1.5 mmHg (Δ31.1±0.9 mmHg, p<0.001). The intermediate and low doses induced MAP rises of 24.3±2.7 mmHg (p<0.001) and 13.4±3.3 mmHg (p<0.001), respectively. The low dose of sunitinib with high salt, induced a MAP rise of 43.5±2.2 mmHg (p<0.001 compared to normal salt). With the high dose, circulating ET-1 increased from 0.6±0.1 pg/ml to 1.6±0.2 pg/ml (p<0.01) and serum cystatine-C from 4.5±0.1 mg/L to 6.6±0.3 mg/L (p<0.001). Comparable increases in circulating ET-1 were seen with the intermediate and low doses, whereas serum cystatine-C did increase with the intermediate dose (to 6.3±0.1 mg/L, p0.05). Serum cystatine-C levels with low and high salt were identical. With the high dose of sunitinib, proteinuria increased from 7.5±1.3 to 33.3±4.8 mg/day (p<0.05). The rise in proteinuria was attenuated with the intermediate (16.2±2.1 mg/day, p<0.01) and low dose (19.9±3.3 mg/day, p<0.01), but increased to 40.4±30.1 mg/day (p>0.05) with high salt. Angiogenesis inhibition-induced hypertension and nephrotoxicity are dose-dependent with a lower threshold for the rise in BP than for renal toxicity. The BP rise observed with the low dose of sunitinib observed in normotensive rats is comparable to the sunitinib-induced BP rise observed in patients and clearly is salt-sensitive. Since cystatine-C levels during normal and high salt diet were comparable, the BP rise during high salt seems independent of renal dysfunction.

scholarly journals Carbidopa for Afferent Baroreflex Failure in Familial Dysautonomia

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 724-731
Author(s):  
Lucy Norcliffe-Kaufmann ◽  
Jose-Alberto Palma ◽  
Jose Martinez ◽  
Horacio Kaufmann
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
Low Dose ◽  
Familial Dysautonomia ◽  
Reduce Blood Pressure ◽  
Catecholamine Release ◽  
High Dose ◽  
Double Blind ◽  
Adequate Treatment ◽  
Baroreflex Failure

Afferent lesions of the arterial baroreflex occur in familial dysautonomia. This leads to excessive blood pressure variability with falls and frequent surges that damage the organs. These hypertensive surges are the result of excess peripheral catecholamine release and have no adequate treatment. Carbidopa is a selective DOPA-decarboxylase inhibitor that suppresses catecholamines production outside the brain. To learn whether carbidopa can inhibit catecholamine-induced hypertensive surges in patients with severe afferent baroreflex failure, we conducted a double-blind randomized crossover trial in which patients with familial dysautonomia received high dose carbidopa (600 mg/day), low-dose carbidopa (300 mg/day), or matching placebo in 3 4-week treatment periods. Among the 22 patients enrolled (13 females/8 males), the median age was 26 (range, 12–59 years). At enrollment, patients had hypertensive peaks to 164/116 (range, 144/92 to 213/150 mm Hg). Twenty-four hour urinary norepinephrine excretion, a marker of peripheral catecholamine release, was significantly suppressed on both high dose and low dose carbidopa, compared with placebo ( P =0.0075). The 2 co-primary end points of the trial were met. The SD of systolic BP variability was reduced at both carbidopa doses (low dose: 17±4; high dose: 18±5 mm Hg) compared with placebo (23±7 mm Hg; P =0.0013), and there was a significant reduction in the systolic BP peaks on active treatment ( P =0.0015). High- and low-dose carbidopa were similarly effective and well tolerated. This study provides class Ib evidence that carbidopa can reduce blood pressure variability in patients with congenital afferent baroreflex failure. Similar beneficial effects are observed in patients with acquired baroreflex lesions.

Sedative and physiologic effects of tiletamine–zolazepam following buccal administration in cats

2019 ◽  
Vol 22 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Pablo Nejamkin ◽  
Verónica Cavilla ◽  
María Clausse ◽  
Florencia Landivar ◽  
Augusto M Lorenzutti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Low Dose ◽  
Sedation Score ◽  
High Dose ◽  
Physiological Effects ◽  
Chemical Restraint ◽  
Hemoglobin Saturation ◽  
Baseline Systolic Blood Pressure ◽  
Over Time

Objectives The aim of this study was to describe the sedative and some physiological effects of tiletamine–zolazepam following buccal administration (BA) in cats. Methods Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine–zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. Results All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively ( P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. Conclusions and relevance BA of tiletamine–zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.

Effects of low-dose meloxicam in cats with chronic kidney disease

2020 ◽  
pp. 1098612X2093575
Author(s):  
Kate KuKanich ◽  
Christopher George ◽  
James K Roush ◽  
Sherry Sharp ◽  
Giosi Farace ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Adverse Effects ◽  
Transforming Growth Factor Beta ◽  
Low Dose ◽  
Transforming Growth Factor ◽  
Joint Disease ◽  
Cystatin B

Objectives Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD). Methods Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (ß):creatinine ratio, urine clusterin, urine cystatin B and serum inosine. Results No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-ß:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months ( P = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects. Conclusions and relevance No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.

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