Alterations In Systolic Blood Pressure Research Articles

Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet

BackgroundParental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet.MethodsUsing a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension.ResultsThe offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD.ConclusionOur findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

Association between benign prostate enlargement-related storage and voiding symptoms and systolic blood pressure: a single-center cross-sectional study.

Lower urinary tract symptoms significantly worsen quality of life. The hypothesis that they might lead to serious systolic blood pressure alterations through inducing sympathetic nervous activity has not been studied so far. To investigate the relationship between benign prostate enlargement-related storage and voiding symptoms and systolic blood pressure. Cross-sectional single-center study on data from a hospital patient record system. We evaluated the medical records of all consecutive patients with benign prostate enlargement-related lower urinary tract symptoms admitted between January 2012 and December 2017. Storage and voiding symptoms were assessed separately. International Prostate Symptom Score, uroflowmetry, postvoiding residual urine volume and systolic blood pressure were recorded. Pearson correlation and linear regression analysis were used. Positive correlations were found between systolic blood pressure and all of the storage symptoms. Among these, urgency had the most significant effect. There were 166 patients (41.4%) with urgency for urination, which increased mean systolic blood pressure from 124.88 mmHg (average value in elevated blood pressure group) to 132.28 mmHg (average value in stage-1 hypertension group). Hesitancy in urinating and feeling of incomplete bladder emptying had weak positive correlations with systolic blood pressure. There was a negative correlation between systolic blood pressure and intermittency of urination. With increasing numbers of urine storage symptoms, systolic blood pressure also increases, while the opposite occurs for voiding symptoms in patients with benign prostate enlargement. We conjecture that storage symptoms may lead to this increase through inducing sympathetic hyperactivity. Further prospective studies with larger groups are needed to confirm these findings.

90. Catechol-O-methyltransferase deficiency leads to hypersensitivity on the pressor response against angiotensin II

Catechol-O-methyltransferase (COMT) metabolizes 2-hydroxyestradiol into 2-methoxyestradiol (2-ME); COMT deficiency has been shown to be associated with hypertension in men. Preeclampsia is a disease associated with hypersensitivity of pressor response against angiotensin II (Ang II). Here, we found that COMT deficiency could explain the hypersensitivity of pressor response against Ang II in mice because of the lack of 2-ME-dependent suppression of angiotensin II receptor type 1 (AT1R). Male C57BL/6 mice were subjected to COMT inhibitor (COMTi: 25 mg/kg per day) or oil (control) for 4 weeks, with or without low-dose Ang II infusion (ANGII: 70 ng/kg per minute) for the last 3 weeks. The Ang II-infused mice were treated with 2-ME (10 ng/d) or vehicle for the last 1 week. We obtained the following experimental groups: control, ANGII, COMTi, COMTi + ANGII, and COMTi + ANGII + 2-ME. We performed similar experiments using the in vivo administration of small interfering RNA of COMT instead of COMTi. Neither ANGII nor COMTi exhibited significant alterations in systolic blood pressure. Compared with ANGII or COMTi, COMTi + ANGII displayed significantly higher systolic blood pressure, albuminuria, and glomerular endotheliosis; 2-ME normalized such alterations. Similar phenotypes were observed in COMT small interfering RNA-treated mice. In the aorta of COMT-deficient mice, AT1R expression was increased; 2-ME suppressed AT1R expression. The 2-ME exhibited peroxisome proliferator-activated receptor γ agonistic activity in vitro and ex vivo plasma from pregnant female mice as well. In vitro, 2-ME suppressed both basal and Ang II-induced AT1R levels in a peroxisome proliferator-activated receptor γ-dependent manner. The 2-ME is relevant to combat COMT deficiency-associated hypertensive disorders via suppression of AT1R by its peroxisome proliferator-activated receptor γ activity.

Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats

Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life.

Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment of Obesity

BackgroundDifferent types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling.ObjectiveTo characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified.MethodsThirty-day-old male Wistar rats were randomized into two groups (n = 19 each): control (C; standard diet) and high-fat diet (HF, unsaturated high-fat diet). The initial moment of obesity was defined by weekly measurement of body weight (BW) complemented by adiposity index (AI). Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot.ResultsThe initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%), body fat (20%), AI (14.5%), insulin levels (39.7%), leptin (62.4%) and low-density lipoprotein cholesterol (15.5%) but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05). In addition, there was no changes in the cardiac expression of Ca2+ handling proteins.ConclusionThe initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling.

A variedade da dieta é fator protetor para a pressão arterial sistólica elevada

Diet directly influences systemic arterial hypertension (SAH), which is one of the main risk factors for cardiovascular disease. To associate hypertension with dietary factors in adults clinically selected for a change-of-lifestyle program. Cross-sectional study comprising 335 individuals, aged between 44 and 65 years, clinically selected for a change-of-lifestyle program. We evaluated anthropometric data (BMI, %body fat and waist circumference), biochemical components (plasma glucose, triglycerides, total cholesterol, HDL-C and LDL-c) and diet, through the 24-hour recall method. The quality of the diet was assessed by the Healthy Eating Index. Blood pressure was measured according to the V Brazilian Guidelines on Hypertension and classified according to NCEP-ATPIII. Logistic regression was performed to determine the likelihood of changes in SBP and DBP according to dietary intake. The level of significance was set at p <0.05. There was a positive correlation between diastolic blood pressure and sugar and cholesterol intake, and a negative one with intake of fiber, portions of oil and fats and diet quality. Dietary variety with ≥ 8 food items showed a protective effect for alterations in systolic blood pressure, OR = 0.361 (0.148 to 0.878). A greater dietary variety had a protective effect on the systolic blood pressure.

Hypertension and hematologic parameters in a community near a uranium processing facility

Background Environmental uranium exposure originating as a byproduct of uranium processing can impact human health. The Fernald Feed Materials Production Center functioned as a uranium processing facility from 1951 to 1989, and potential health effects among residents living near this plant were investigated via the Fernald Medical Monitoring Program (FMMP). Methods Data from 8216 adult FMMP participants were used to test the hypothesis that elevated uranium exposure was associated with indicators of hypertension or changes in hematologic parameters at entry into the program. A cumulative uranium exposure estimate, developed by FMMP investigators, was used to classify exposure. Systolic and diastolic blood pressure and physician diagnoses were used to assess hypertension; and red blood cells, platelets, and white blood cell differential counts were used to characterize hematology. The relationship between uranium exposure and hypertension or hematologic parameters was evaluated using generalized linear models and quantile regression for continuous outcomes, and logistic regression or ordinal logistic regression for categorical outcomes, after adjustment for potential confounding factors. Results Of 8216 adult FMMP participants 4187 (51%) had low cumulative uranium exposure, 1273 (15%) had moderate exposure, and 2756 (34%) were in the high (>0.50 Sievert) cumulative lifetime uranium exposure category. Participants with elevated uranium exposure had decreased white blood cell and lymphocyte counts and increased eosinophil counts. Female participants with higher uranium exposures had elevated systolic blood pressure compared to women with lower exposures. However, no exposure-related changes were observed in diastolic blood pressure or hypertension diagnoses among female or male participants. Conclusions Results from this investigation suggest that residents in the vicinity of the Fernald plant with elevated exposure to uranium primarily via inhalation exhibited decreases in white blood cell counts, and small, though statistically significant, gender-specific alterations in systolic blood pressure at entry into the FMMP.

Myosin heavy chain expression in renal afferent and efferent arterioles: relationship to contractile kinetics and function.

The physiological role of smooth muscle myosin heavy chain (MHC) isoform diversity is poorly understood. The expression of MHC-B, which contains an insert at the ATP binding pocket, has been linked to enhanced contractile kinetics. We recently reported that the renal afferent arteriole exhibits an unusually rapid myogenic response and that its kinetic features allow this vessel to modulate tone in response to alterations in systolic blood pressure. In the present study, we examined MHC expression patterns in renal afferent and efferent arterioles. These two vessels regulate glomerular inflow and outflow resistances and control the pressure within the intervening glomerular capillaries (PGC). Whereas the afferent arteriole must respond rapidly to increases in blood pressure, the efferent arteriole plays a distinctly different role, maintaining a tonic elevation in outflow resistance to preserve function when renal perfusion is compromised. Using RT-PCR, Western analysis, and immunofluorescence imaging of intact isolated arterioles, we found that the afferent arteriole predominantly expresses the MHC-B isoform, whereas the efferent arteriole expresses only the slower-cycling MHC-A isoform. We examined the kinetics of angiotensin II- and norepinephrine-induced vasoconstriction and found that the afferent arteriole responds approximately 3-fold faster than the efferent arteriole. Our findings thus point to the renal microcirculation as a unique and important example of smooth muscle adaptation in regard to MHC isoform expression and physiological function.

Essential role of AT1A receptor in the development of 2K1C hypertension.

The aims of this study were to delineate the relative contribution of angiotensin II (ANG II) subtype 1A (AT1A) and 1B (AT1B) receptors to the development of two-kidney, one-clip (2K1C) Goldblatt hypertension in mice, to examine if increased nitric oxide synthase (NOS) activity counteracts the vasoconstrictor influences of ANG II in 2K1C hypertensive mice, and to determine the role of ANG II type 2 (AT2) receptors in 2K1C hypertension in mice. AT(1A) ANG II receptor knockout (AT1A-/-) and wild-type (AT1A+/+) mice underwent clipping of the right renal artery. Systolic blood pressure (SBP) was significantly lower in AT1A-/- compared with AT1A+/+ mice, and neither clip placement nor AT2 receptor blockade with PD 123319 (PD) altered SBP in AT1A-/- mice. A significant and sustained rise in SBP from 119+/-5 to 163+/-6 mm Hg was observed in the 2K1C AT1A+/+ mice from day 10 to day 26. Chronic PD infusion did not alter the course of hypertension in 2K1C/AT1A+/+. Acute PD infusion did not alter mean arterial pressure (MAP) in AT1A+/+, PD/AT1A+/+, 2K1C/AT1A+/+, PD/2K1C/AT1A+/+, AT1A-/-, PD/AT1A-/-, and PD/2K1C/AT1A-/- mice compared with basal levels. In contrast, acute PD infusion caused significant increases in MAP in 2K1C/AT1A-/- mice. The subsequent acute NOS inhibition caused greater increases in MAP in 2K1C/AT1A+/+ and PD/2K1C/AT1A+/+ mice than in AT1A+/+ and PD/AT1A+/+ mice. These results support the essential role of AT1A receptors in mediating 2K1C hypertension and support the hypothesis that augmented NO production serves as a counteracting system in this model of hypertension.

Systolic blood pressure alterations during hyperinsulinemia are related to changes in ionized calcium status

Background:A correlation between changes in ionized calcium status and changes in systolic blood pressure (BP) has previously been observed during induced euglycemic hyperinsulinemia in patients with essential hypertension. The objective of this study was to evaluate associations between alterations in ion status and BP changes during euglycemic hyperinsulinemia in healthy normotensive subjects. Methods:Ion status in plasma and BP were measured before and at the end of euglycemic hyperinsulinemic clamp tests performed in 41 healthy normotensive volunteers. Results:During euglycemic hyperinsulinemia plasma sodium increased by 1% (P < .0001), ionized calcium (iCa) by 5% (P < .0001), and ionized magnesium (iMg) by 4% (P < .01), whereas potassium decreased by 10% (P < .0001). The changes in plasma iCa and iMg correlated significantly to changes in systolic BP (r = −0.38, P < .02; r = −0.32, P < .05, respectively), but the correlation between changes in iMg and changes in systolic BP did not remain significant in a multiple regression model. The glucose infusion rate correlated inversely to the change in iMg (r = −0.39, P < .01). Conclusions:The group mean systolic BP was unaltered during induced euglycemic hyperinsulinemia in healthy normotensive subjects; however, a more pronounced increase in the circulating iCa concentration was associated with a greater decline in systolic BP, which is in accordance with previous observations in patients with essential hypertension. The group mean diastolic BP was decreased; however, the lowered diastolic BP was not correlated to changes in ion status.

Cardiovascular autonomic regulation in asthmatic children evidenced by spectral analysis of heart rate and blood pressure variability.

The objective of the study was to investigate the features of cardiovascular and respiratory autonomic nervous regulation in asthmatic and control children. Cardiorespiratory reactivity was studied by continuous and non-invasive recording of the electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions and during a deep breathing test in 19 children with bronchial asthma and 10 healthy control children (age 8-11 years). The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. Nine asthmatic children without beta2-agonist medication had a lower respiratory rate and larger high frequency (HF) variability of SAP than the controls, and 10 asthmatic children with beta2-agonist medication had greater low-frequency (LF) variability of SAP and LF/HF ratio of R-R intervals, but their respiratory rate did not differ from the controls. No intergroup differences were found in the postural change of variables. Stable bronchial asthma appears to increase respiratory-induced alterations in systolic blood pressure in children. Beta2-agonist medication, on the other hand, increases sympathetic cardiovascular activity in children with asthma.

Long-term prediction of coronary heart disease mortality in two rural Greek populations.

In 1960-61 two pooled Greek rural populations totalling 1215 men aged 40-59 years were followed-up for 25 years. A Cox model analysis of fatal coronary events over 15 years showed that serum cholesterol in men aged 40-59 years, cholesterol in men aged 45-64 years, and systolic blood pressure in men aged 50-69 played a predictive role. The coefficient of age became more significant with advancing age and that of cigarette smoking only at 25 years follow-up. The coefficient of cholesterol decreased stepwise and became negative for men aged 50-69; body mass index was without effect in any follow-up of these cohorts. Systolic blood pressure and serum cholesterol increased in these populations by 5.4 mmHg and 23.5 mg.dl-1 (0.61 mmol.l-1), respectively between the years 0 and 10, whereas cigarette consumption decreased minimally. These changes were used to test the predictability of coronary events occurring between years 10 and 25 of follow-up when added to the model containing the factors at entry. Of these changes only systolic blood pressure significantly increased the predictability of coronary deaths. It is concluded that even minor alterations in systolic blood pressure above or below the entry levels can be associated with marked modifications in coronary mortality above or below those occurring naturally in the 15 years after the changes occurred.