Early Administration of Angiotensin-Converting Enzyme Inhibitor Captopril, Prevents the Development of Hypertension Programmed by Intrauterine Exposure to a Maternal Low-Protein Diet in the Rat

1998 ◽  
Vol 94 (4) ◽  
pp. 373-381 ◽  
Author(s):  
Rachel C. Sherman ◽  
Simon C. Langley-Evans
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Control Diet ◽  
Female Offspring ◽  
Fetal Exposure ◽  
Early Administration ◽  
Low Protein ◽  
Blood Pressures ◽  
Protein Diets

1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of ‘programmed’ hypertension was used to investigate the role of the renin—angiotensin system in the initiation and maintenance of high blood pressure. 2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24–25 mmHg higher than those of rats exposed to a control diet in utero. 4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopriltreated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero. 6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early administration of an angiotensin-converting enzyme inhibitor. The actions of angiotensin II in the late suckling period may be a critical determinant of long-term cardiovascular functions in these animals.

Maternal Carbenoxolone Treatment Lowers Birthweight and Induces Hypertension in the Offspring of Rats Fed a Protein-Replete Diet

1997 ◽  
Vol 93 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Simon C. Langley-Evans
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Fetal Growth ◽  
Low Birthweight ◽  
Control Diet ◽  
Later Life ◽  
Hydroxysteroid Dehydrogenase ◽  
Fetal Exposure ◽  
Low Protein ◽  
Protein Diets

1. In the rat low birthweight and raised systolic blood pressure are the consequence of fetal exposure to maternal low protein diets. Nutritional down-regulation of the placental isoform of 11β-hydroxysteroid dehydrogenase, which may increase exposure of the fetus to maternal glucocorticoids, has been suggested to underlie effects of low protein diets on fetal growth and blood pressure. 2. Pregnant rats were fed control (18% casein) or low protein (9% casein) diets throughout gestation. Animals fed the control diet were injected with carbenoxolone, an inhibitor of 11β-hydroxysteroid dehydrogenase. Injections were administered either throughout pregnancy (days 0–22), or targeted to specific periods in early (days 0–7), mid- (days 8–14) or late (days 15–22) gestation. 3. Exposure to a low protein diet reduced birthweight and at 4 weeks of age systolic blood pressure was significantly elevated in the rats exposed to low protein. These hypertensive animals had small kidneys in proportion to body weight. 4. Fetal exposure to carbenoxolone at any period in gestation resulted in lower weight at birth. In rats exposed to the inhibitor over days 8–14, 15–22 or 0–22 systolic blood pressure at 4 weeks was significantly higher than in control animals. The greatest elevation of pressure was associated with carbenoxolone treatment in late (days 15–22) gestation. Animals with carbenoxolone-induced hypertension did not exhibit evidence of retarded renal growth. 5. Increased fetal exposure to maternal glucocorticoids impairs fetal growth and programmes elevated blood pressure in later life.

Weanling Rats Exposed to Maternal Low-Protein Diets during Discrete Periods of Gestation Exhibit Differing Severity of Hypertension

1996 ◽  
Vol 91 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Simon C. Langley-Evans ◽  
Simon J. M. Welham ◽  
Rachel C. Sherman ◽  
Alan A. Jackson
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Plasma Renin ◽  
Late Gestation ◽  
Protein Diet ◽  
Male Rats ◽  
Low Protein Diet ◽  
Fetal Exposure ◽  
Low Protein ◽  
Protein Diets

1. In the rat, hypertension is induced by fetal exposure to maternal low-protein diets. The effect on blood pressure of undernutrition before conception and during discrete periods in early, mid or late pregnancy was assessed using an 18% casein (control) diet and a 9% casein diet to apply mild protein restriction. 2. The offspring of rats fed 9% casein developed raised blood pressure by weaning age. Feeding a low-protein diet before conception was not a prerequisite for programming of hypertension. 3. Hypertension was observed in rats exposed to low protein during the following gestational periods: days 0–7, days 8–14 and days 15–22. Blood pressure increases elicited by these discrete periods of undernutrition were lower than those induced by feeding a low-protein diet throughout pregnancy. The effect in early gestation was significant only in male animals. Post-natal growth of male rats exposed to low-protein diets was accelerated, but kidneys were small in relation to body weight. 4. Biochemical indices of glucocorticoid action in liver, hippocampus, hypothalamus and lung were elevated in rats exposed to low-protein diets in utero. The apparent hypersensitivity to glucocorticoids was primarily associated with undernutrition in mid to late gestation. 5. Plasma renin activity was elevated in rats exposed to 9% casein over days 15–22 of gestation. Animals undernourished over days 0–7 and 8–14 produced pups with lower plasma angiotensin II concentrations at weaning. 6. Fetal exposure to maternal low-protein diets for any period in gestation may programme hypertension in the rat. Alterations to renal structure, renal hormone action or the hypothalamic—pituitary-adrenal axis may all play a role in the programming phenomenon, either independently or in concert.

Maternal quercetin intake during lactation attenuates renal inflammation and modulates autophagy flux in high-fructose-diet-fed female rat offspring exposed to maternal malnutrition

2019 ◽  
Vol 10 (8) ◽  
pp. 5018-5031 ◽  
Author(s):  
Shin Sato ◽  
Toshio Norikura ◽  
Yuuka Mukai
Keyword(s):  
Female Offspring ◽  
Female Rat ◽  
Autophagy Flux ◽  
Maternal Malnutrition ◽  
High Fructose Diet ◽  
Rat Offspring ◽  
Low Protein ◽  
High Fructose ◽  
Protein Diets

Quercetin intake during lactation causes long-term alterations in inflammation and autophagy flux in the kidneys of high-fructose-diet-fed adult female offspring exposed to maternal normal- or low-protein diets.

Prenatal programming of adult blood pressure: role of maternal corticosteroids

2005 ◽  
Vol 289 (4) ◽  
pp. R955-R962 ◽  
Author(s):  
Lori L. Woods ◽  
Douglas A. Weeks
Keyword(s):  
Blood Pressure ◽  
Food Intake ◽  
Female Offspring ◽  
Common Mechanism ◽  
Long Term Effects ◽  
Pregnant Rats ◽  
Body Weights ◽  
Glucocorticoid Administration ◽  
Blood Pressures

Both maternal glucocorticoid administration and maternal dietary protein or food restriction in pregnancy cause fewer nephrons and hypertension in the adult offspring. The purpose of these studies was to determine the extent to which nutritional factors contribute to programming of offspring hypertension by maternal glucocorticoids. Pregnant rats were treated with dexamethasone (100 μg·kg−1·d−1sc) on days 1–10 (ED) or days 15–20 (LD) of pregnancy. Additional groups of pregnant animals were pair fed to the early (EDPF) and late (LDPF) dexamethasone-treated groups, and another group was untreated or given vehicle (C). The dams treated with dexamethasone reduced their food intake and lost or failed to gain a normal amount of weight during treatment; body weights of ED dams caught up to normal after the treatment period, whereas those of LD dams did not. In adulthood (∼21 wks), chronically instrumented male offspring of ED had normal blood pressures (125 ± 2 mmHg vs. 126 ± 1 mmHg in C), whereas LD offspring were hypertensive (136 ± 3 mmHg). However, LDPF offspring were equally hypertensive (134 ± 2 mmHg). Glomerular filtration rates normalized to body weight were not significantly different among groups. Qualitatively similar results were found in female offspring. Thus the long-term effects of maternal glucocorticoid administration at this dose on offspring’s blood pressure may, in large part, be accounted for by the reduction in maternal food intake. These data suggest that maternal glucocorticoids and maternal food or protein restriction may, at least in part, share a common mechanism in programming offspring for hypertension. The window of sensitivity of future offspring blood pressure to either maternal insult coincides with nephrogenesis in the rat, suggesting that impaired renal development could play an important role in this programming.

scholarly journals Does 20 mg long-acting methylphenidate alter blood pressure and heart rate in children with ADHD?

2011 ◽  
Vol 51 (5) ◽  
pp. 282
Author(s):  
Tjhin Wiguna ◽  
Sasanto Wibisono ◽  
Sudigdo Sastroasmoro ◽  
Fransiscus D. Suyatna
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiovascular Effects ◽  
Children With Adhd ◽  
Normal Ranges ◽  
Blood Pressures ◽  
Drug Naïve ◽  
Repeated Analysis ◽  
Long Acting

Objective To identify the cardiovascular effects of long-acting methylphenidate administered for twelve weeks in Indonesian children with ADHD.Methods This was an 18-week, time series study on children with ADHD who were given 20 mg of long-acting methylphenidate for twelve weeks. During the study period we made ten serial observations of the subjects, including before, during and 6 weeks following drug administration. We included drug naive children with ADHD between the ages of 7 – 10 years. Children with mental retardation and chronic physical or mental disorders were excluded. Blood pressure was measured by sphygmomanometer with a child’s cuff at the brachial artery. We also collected data on heart rate, side effects, complaints and other medications used during the study. Repeated analysis was performed on the data with a P level of 0.05.Results Twenty-one subjects were recruited for this study. Mean blood pressure fluctuated insignificantly during the research period, for both mean systolic and mean diastolic blood pressures (P=0.115 and P=0.059). Mean heart rate also fluctuated insignificantly (P=0.091). All fluctuations were within the normal ranges. During the study, there were complaints of dizziness, nausea, and gastrointestinal upset, but they were reportedly mild and disappeared before the second week of observation.Conclusion Administration of 20 mg long-acting methylphenidate for twelve weeks in children with ADHD altered mean blood pressures and heart rates, but within the normal range for children of their age. However, cardiovascular risk observation is still needed when administering methylphenidate to children with ADHD, especially for those using the medication long-term.[Paediatr Indones. 2011;51:282-7].

scholarly journals P1462IMPACT OF HEART RATE AND BETA-BLOCKER USE ON THE LONG-TERM SURVIVAL OF CHRONIC HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Takuhiro Moromizato ◽  
Kunitoshi Iseki ◽  
OCTOPUS Study Group
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cox Regression ◽  
Chronic Hemodialysis ◽  
Time Varying ◽  
Term Survival ◽  
Blood Pressures ◽  
Β Blocker ◽  
Time Varying Covariates

Abstract Background and Aims Increase in resting heart rate might influence mortalities of dialysis patients, and the use of β-blocker might improve their survival probability. However, the influence of heart rate and benefits of β-blocker on their survival are difficult to quantify because of following obstacles: prone to measurement errors; inherent association of heart rate with blood pressures, comorbidities, and medication use; and a necessity of repeated measurements of vital signs and medication use. Therefore, at the design process of our previous randomized control trial on the Olmesartan Clinical Trial in Okinawan patients under OKIDS (OCTOPUS), we included the repeated measures design to quantify the influence of vital sign values on the survival retrospectively. We combined the repeated measurement data and additional the long-term prognosis information of the participants obtained after the OCTOPUS with aim of investigating the influence of time varying covariates: heart rates, blood pressures, and β-blocker use, on the long-term survival of hemodialysis patients. Method We investigated 461 adult OCTOPUS participants who received chronic hemodialysis and antihypertensive medications in Okinawa. The OCTOPUS trial, which was conducted between June 2006 and June 2011, did not detect the survival benefit of angiotensin receptor blocker (ARB)NDT 2013, but the study and the additional follow-up of participants’ prognosis provided us with information to investigate influence of predictors on long-term survival in the population. Throughout the OCTOPUS trial, study participants were measured pre-dialysis blood pressures, pre-dialysis resting heart rates, and their medication use for one week at their dialysis centers every six months after their participations. Following the trial, we collected the prognosis information of all participants until July 31st, 2018. Finally, we merged the multiple-measured data during the OCTOPUS with the prognosis data. Mean values of three measurements of blood pressures and heart rates and β-blocker use were introduced to the Cox-regression model as time-varying covariates with essential non-time varying covariates, which include age, gender, and diabetes. Results In this retrospective cohort study, 221 (47.9%) out of 461 participants deceased, and the median follow-up length was 10.21 years. Initial mean resting heart rate and pre-dialysis mean blood pressure were 78(±10) per minute and 159.5(±14) mmHg, respectively. 10% of participants were prescribed β-blocker initially. The resting heart rate of all participants significantly decreased by 1.75 and 2.45 per minutes after two and four years respectively. β-blocker could significantly decrease the mean heart rate by 3.54 and 2.90 per minutes after two and four years. With our Cox-regression with the time varying covariates, increase of heart rate was significantly associated with higher mortality (P=0.002), but the use of β-blocker was not associated with the mortality. (P=0.691) Additionally, we could not detect the interaction of heart rate and β-blocker use on the mortality. (P= 0.796) Although lower blood pressure was significantly associated with higher mortality in our initial Cox-regression analysis, an introduction of interaction term of heart rate and blood pressure remove the significance of influence of blood pressure on the survival. Conclusion In hypertensive chronic hemodialysis patients, higher heart rate is associated with higher mortality. However, use of beta-blocker was not associated with improvement of their mortality.

Dietary sodium restriction and development of hypertension in spontaneously hypertensive rats

1983 ◽  
Vol 245 (6) ◽  
pp. H1081-H1084 ◽  
Author(s):  
C. B. Toal ◽  
F. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Dietary Sodium ◽  
Sodium Restriction ◽  
Spontaneously Hypertensive ◽  
Basal Blood Pressure ◽  
Blood Pressures ◽  
Dietary Sodium Restriction ◽  
Wistar Kyoto ◽  
And Control

Blood pressure and body weight of conscious spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were measured up to 16 wk of age in animals started at birth on five different sodium-containing diets. SHR on 9 mumol sodium/g food did not show a rise in basal blood pressure; however, when stressed the SHR still exhibited slightly higher blood pressures than WKY. In SHR on 17 mumol sodium/g food the development of hypertension was blunted compared with that of control (101 mumol/g) diet animals. SHR on 26 or 44 mumol sodium/g diet exhibited a development of hypertension similar to that of SHR on control diet. The 26 mumol/g, 44 mumol/g, and control sodium diet groups, regardless of strain, had similar growth rates. By contrast, on 17 mumol sodium/g food both SHR and WKY showed a substantially reduced growth rate, and all animals on 9 mumol sodium/g diet were severely retarded in growth. The results indicate that dietary sodium restriction can ameliorate the development of hypertension in SHR, but only when the sodium levels are so low as to affect overall growth.

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