Hydrochlorothiazide Reduces Cardiac Hypertrophy, Fibrosis and Rho-Kinase Activation in DOCA-Salt Induced Hypertension

Author(s):  
David Mondaca-Ruff ◽  
Patricio Araos ◽  
Cristián E. Yañez ◽  
Ulises F. Novoa ◽  
Italo G. Mora ◽  
...  

Background: Thiazides are one of the most common antihypertensive drugs used for hypertension treatment and hydrochlorothiazide (HCTZ) is the most frequently used diuretic for hypertension treatment. The Rho/Rho-kinase (ROCK) path plays a key function in cardiovascular remodeling. We hypothesized that in preclinical hypertension HCTZ reduces myocardial ROCK activation and consequent myocardial remodeling. Methods: The preclinical model of deoxycorticosterone (DOCA)-salt hypertension was used (Sprague–Dawley male rats). After 3 weeks, in 3 different groups: HCTZ, the ROCK inhibitor fasudil or spironolactone was added (3 weeks). After 6 weeks myocardial hypertrophy and fibrosis, cardiac levels of profibrotic proteins, mRNA levels (RT PCR) of pro remodeling and pro oxidative molecules and ROCK activity were determined. Results: Blood pressure, myocardial hypertrophy and fibrosis were reduced significantly by HCTZ, fasudil and spironolactone. In the heart, increased levels of the pro-fibrotic proteins Col-I, Col-III and TGF-β1 and gene expression of pro-remodeling molecules TGF-β1, CTGF, MCP-1 and PAI-1 and the pro-oxidative molecules gp91phox and p22phox were significantly reduced by HCTZ, fasudil and spironolactone. ROCK activity in the myocardium was increased by 54% ( P < 0.05) as related to the sham group and HCTZ, spironolactone and fasudil, reduced ROCK activation to control levels. Conclusions: HCTZ reduced pathologic LVH by controlling blood pressure, hypertrophy and myocardial fibrosis and by decreasing myocardial ROCK activation, expression of pro remodeling, pro fibrotic and pro oxidative genes. In hypertension, the observed effects of HCTZ on the myocardium might explain preventive outcomes of thiazides in hypertension, specifically on LVH regression and incident heart failure.

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zheng ◽  
Tao Huang ◽  
Qi-Zhen Tang ◽  
Shi Li ◽  
Jie Qin ◽  
...  

Background:Astragalus polysaccharide extract (APS) has been shown to exhibit antioxidant and anti-inflammatory potential in the treatment of several diseases. However, whether APS could protect against renal damage in hypertensive mice is unknown.Methods: Hematoxylin and eosin staining, immunohistochemistry, real-time polymerase chain reaction, and Western blotting were used to investigate the effect of APS on the renal damage in deoxycorticosterone acetate- (DOCA) salt- and angiotensin II- (Ang II-) induced hypertensive mice and to elucidate the underlying mechanisms.Results: Our data demonstrated that APS significantly reduced blood pressure in DOCA-salt- and Ang II-treated mice. Furthermore, APS reduced the inflammatory response and renal fibrosis, thereby improving renal function. Furthermore, the levels of serum creatinine, urea nitrogen, and uric acid increased in DOCA-salt-treated mice, alleviated by APS administration. At the molecular level, DOCA-salt and Ang II increased the mRNA levels of IL-1β, IL-6, α-SMA, collagen I, and collagen III, while APS significantly inhibited these effects. APS inhibited the TGF-β1/ILK signaling pathway, which was activated in hypertensive mice due to the administration of DOCA-salt.Conclusion: Our results suggest that APS plays a beneficial role in improving renal dysfunction in hypertensive mice.


2002 ◽  
Vol 120 (4) ◽  
pp. 100-104 ◽  
Author(s):  
Juvenal Soares Dias da Costa ◽  
Sandra Costa Fuchs ◽  
Maria Teresa Anselmo Olinto ◽  
Denise Petrucci Gigante ◽  
Ana Maria Baptista Menezes ◽  
...  

CONTEXT: The cost-effectiveness of the treatment of hypertension has scarcely been investigated in population-based studies. Most data come from secondary analysis of clinical trials and administrative sources. OBJECTIVE: To describe the healthcare costs for outpatient hypertension treatment in comparison with diabetes mellitus and chronic bronchitis, and to examine the cost-effectiveness of different classes of antihypertensive drugs. DESIGN: Cross-sectional population-based study. SETTING: Urban area of Pelotas, southern Brazil. PARTICIPANTS: Individuals aged 20-69 years, identified through multi-stage probability sampling. METHODS: Participants were interviewed at home. Demographic data, education, income, smoking, previous morbidity, use of medicine and other characteristics were assessed via a pre-tested questionnaire, and blood pressure while seated was measured in a standardized way. RESULTS: Approximately 24% of the participants had high blood pressure or were taking antihypertensive drugs, and among these, 33% had had a physician consultation during the month preceding the interview. The monthly mean costs of care for hypertension (R$ 89.90), diabetes (R$ 80.64) and bronchitis (R$ 92.63) were similar. Treatment of hypertension consumed 22.9% of the per-capita income, corresponding to R$ 392.76 spent per year exclusively on antihypertensive drugs. Most of the direct costs associated with hypertension and diabetes were spent on drugs, while patients with bronchitis had greater expenditure on appointments. The cost-effectiveness relationship was more favorable for diuretics (116.3) and beta blockers (228.5) than for ACE inhibitors (608.5) or calcium channel blockers (762.0). CONCLUSION: The costs of hypertension care are mainly dependent on the expenditure on blood pressure-lowering drugs. Treatment of hypertension with diuretics or beta blockers was more cost-effective than treatment with ACE inhibitors and calcium channel blockers.


1983 ◽  
Vol 244 (2) ◽  
pp. H234-H238
Author(s):  
J. R. Nichols ◽  
R. L. Clancy ◽  
N. C. Gonzalez

The effect of coarctation of the abdominal aorta (AC) and of sham operation (SO) on the development of myocardial hypertrophy was studied in three groups of male rats, i.e., a group without treatment prior to AC or SO (untreated), a group with bilateral adrenalectomy (ADX) 5-7 days before AC or SO, and a group in which the adrenal medulla was removed (MDX) 5-7 days before AC or SO. MDX resulted in functional elimination of the adrenal medulla without apparent effect on cortical function. The animals were killed 7-10 days after AC or SO. AC produced carotid blood pressure (CBP) increases of 33, 31, and 25 mmHg in the untreated, ADX, and MDX groups, respectively. Ventricular weight (HW), ventricular RNA concentration, and RNA-to-DNA ratio increased significantly after AC only in the untreated and MDX groups. In the ADX group, hypertension was followed by an increase in HW that could be detected only after normalization for body weight. It is concluded that absence of the adrenal gland significantly reduces the development of pressure-induced myocardial hypertrophy. Apparently, this is due to the absence of the adrenal cortex and not absence of the adrenal medulla.


2019 ◽  
Vol 7 (1) ◽  
pp. 636-641
Author(s):  
Glory Grifith B. Saragih ◽  
Jeanny Rantung

Introduction: In 2016 West Java was the fourth ranked province as the region with the highest prevalence of hypertension, which was 29.4% in Indonesia. Failure to treat hypertension was found due to low compliance in the use of hypertension drugs. Non-compliance with the consumption of antihypertensive drugs will have an impact on the incidence of uncontrolled blood pressure. Long term Uncontrolled blood pressure can cause complications of disease and even death. The purpose of this study is to identify the overview of hypertensive patients in consuming hypertension drugs. Method: This study uses a qualitative method with a phenomenological approach. Result: From this study it was found that taking medication for a long period of time caused a feeling of laziness and boredom in taking medicine, resulting in patients with hypertension stopped consuming medication. Fear of side effects from taking medication for a long period of time makes hypertensive patients decided to stop the consumption of hypertension medicine. Discussion is hoped that this research can be an input to improve health promotion to reduce the failure of hypertension treatment.


2015 ◽  
Vol 6 (2) ◽  
pp. 64-68
Author(s):  
O. A Kislyak ◽  
A. V Starodubova

Arterial hypertension (AH) is the most common cardiovascular disease risk factor. After the menopause the prevalence of AH in women greatly exceeds than in men. Hemodynamic characteristics in case of AH in postmenopausal women determine the higher risk and the speed of left ventricle myocardial hypertrophy (LMVH), diastolic and systolic dysfunction development. There 80 women aged 44-62 years (mean age of 53.2±4.1 years) in the early postmenopausal period were enrolled in the study and we found that the main influence on LV mass index and LMVH in addition to AH and the level of systolic blood pressure play the body mass index, the level of diastolic blood pressure and the indicators characterizing the distribution of adipose tissue, presence of abdominal obesity. Guidelines for the treatment of AH in men and women have no fundamental differences. However, taking into account the high prevalence of obesity, isolated systolic hypertension and LMVH in women with AH in postmenopausal period, the drugs of choice become angiotensin receptor blocker (ARBs) and the combinations of antihypertensive drugs on the basis of the ARBs, all these data for the first time ever were shown in the study LIFE concerning the application of losartan in the treatment.


2020 ◽  
pp. 30-40
Author(s):  
M. G. Melnik

Purpose. To study the dynamics of blood pressure (BP) indicators under the influence of exogenously administered melatonin (Melatonin-SZ, Severnaya Zvezda, Russia) with various manifestations of desynchronosis of circadian BP rhythms (arterial hypertension – AH, high normal blood pressure) to determine the scheme of their effective compensation. Material and methods. The study included 101 patients with desynchronosis of circadian rhythms of blood pressure – 52 patients with hypertension, constituting the first and second groups, and 49 individuals with high normal blood pressure, representing the third and fourth groups. Patients of the second and fourth groups received conservative therapy, patients of the first and third groups combined it with melatonin. All patients underwent measurements of office blood pressure, home monitoring of blood pressure (ABPM), electrocardiography, 24-hour blood pressure monitoring (ABPM). Results and discussion. In patients of the first and third groups, compared with the traditional treatment groups, by the end of the observation period, a significantly (p < 0.05) decrease in office systolic blood pressure (SBP) / diastolic blood pressure (DBP) was established: in the first group compared with the second – 1.11 / 1.13 times, in the third group compared to the fourth – 1.43 / 1.58 times; significantly more (p < 0.05) pronounced decrease in SBP / DBP during DMAD – by 1.08 / 1.17 and 1.58 / 1.62 times, respectively, Significantly (p < 0.05) more pronounced decrease in average daily, average daily and average nighttime SBP / DBP during ABPM – by 1.13 / 1.20, 1.11 / 1.20, 1.23 / 1.25 and 1.47 / 1.31, 1.42 / 1.19, 1.54 / 1.41 times, respectively; reliably (p < 0.05) more frequent registration of the dipper rhythm type SBP / DBP – 1.6 / 1.4 and 1.6 / 1.4 times, respectively. In addition, the dynamics of patients in the first and third groups showed a significant (p < 0.05) decrease in the mean daily and mean nighttime SBP / DBP variability (SBP in the first group by 27.3 and 41.3 %, respectively; DBP in the first group by 20.1 and 26.3 %, respectively; SBP in the third group by 13.5 and 25.2 %, respectively; DBP in the third group by 12.2 and 28.2 %, respectively). Conclusions. With various manifestations of desynchronosis of circadian rhythms of blood pressure (AH, high normal blood pressure), the prescription of melatonin (Melatonin-SZ, Severnaya Zvezda, Russia) at a dose of 3 mg per day 30–40 minutes before bedtime for a month against the background of non-drug therapy and antihypertensive drugs led to a significantly more effective decrease in blood pressure at its office measurement, DMAD, ABPM with an improvement in the circadian rhythm of blood pressure and normalization of blood pressure variability.


2016 ◽  
pp. 76-84
Author(s):  
Khoa Bao Chau Thai ◽  
Thi Hong Phuong Vo

Background: Hypertension is a common condition in the world as well as in Viet Nam. If hypertension isn’t treated well, it can cause many serious complications. Controlling target blood pressure will bring positive effects on reducing mortality rate and also disabilities caused by diseases related to hypertension. Objectives: (1) Analyzing the use of medicines in treating hypertension. (2) Evaluating the effects of medicine usage in treating hypertension at the hospital of Hue University of Medicine and Pharmacy. Materials and methods: 388 patients were diagnosed as having hypertension with inpatient care at the Cardiovascular Department of Hue University of Medicine and Pharmacy’s hospital, using cross-sectional descriptive study methods. Results: All antihypertensive drugs in the research were contained in the antihypertensive list recommended by Vietnamese Society of Cardiology. Angiotensin converting enzyme inhibitor and calcium channel blocker were the two most popular drug groups (96.6% and 71.4%, respectively). The rate of using multi-therapy regimens was higher than the rate of using uni-therapy regimens in both initial therapies (64.7%>35.3%) and final therapies (61.9%>38.1%). The rate of patients having interactions between antihypertensive drugs and the other kinds of drugs was 7.5%. The rate of patients having reasonable prescriptions was 84.3%. Evaluating the effects of medicine usage in treatments showed that the rate of patients reaching target blood pressure before leaving the hospital was 67.3%. Most patients were evaluated as having good prognosis after treatment, up to 81.7%. Conclusions: All antihypertensive drugs in the research were contained in the antihypertensive list recommended by Vietnamese Society of Cardiology. The rate of using multi-therapy regimens was higher than the rate of using uni-therapy regimens. The rate of drug interactions was quite low; most patients were evaluated as having good prognosis after treatment. Key words: hypertension, antihypertensive drugs.


2019 ◽  
Vol 20 (1) ◽  
pp. 75-84

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy


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