Serotonin-mediated cardiovascular responses to electrical stimulation of the raphe nuclei in the rat.

The dorsal and median raphe nuclei in rats were electrically stimulated and blood pressure and heart rate were recorded. Stimulation of each raphe nucleus caused an increase in blood pressure without affecting heart rate. The size of the increase in blood pressure depended upon the stimulus-intensity.Significant increases were already obtained with 5 sec. trains of 0.3 msec., 200 μA stimuli given at a frequency of 50 Hz. The increases in blood pressure could be obtained with electrodes within the raphe nuclei.Pretreating rats with para-chlorophenylalanine (pCPA, 100 mg/kg.day for 3 days) significantly diminished the increases in blood pressure obtained during electrical stimulation of the median raphe nucleus. However, similar pretreatment did not affect blood pressure rises induced by dorsal raphe stimulation.These data are discussed in relation to the role of central serotoninergic mechanisms in cardiovascular control.     

The relationship of family income,family size,age and circumferences with blood pressure in the female students of the Bahauddin Zakariya University,Multan, Pakistan

In a randomly selected sample of 600 female students of the Bahauddin Zakariya University, Multan, Pakistan, belonging to different socioeconomic groups, age, family income and family size were recorded and measurements were made of arm, waist, neck and total circumferences, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). The correlation coefficients between different independent (age, family income, family size, arm, waist, neck and total circumference) and dependent variables (SBP, DBP and MAP) showed that age had a strong association (p < 0.001) with all types of blood pressure, whereas the correlation coefficient of family income and family size was significant with SBP (p < 0.05) and non-significant with DBP and MAP. Moreover, all the circumferences had strong relationship (p 0.05 at least) with blood pressure. The regression coefficients of age were highly significant for SBP, DBP and MAP, whereas these were non-significant (p > 0.05) for family income and family size. The regression coefficients for arm and waist were significant (p < 0.05), whereas these were highly significant (p < 0.01 at least) for neck and total circumferences. The neck had a 0.46 mm Hg/cm with SBP, 0.41 mm Hg/cm for DBP and 0.44 Hg/cm for MAP, and these were highest among the circumferences.     

Association of birth weight and current body size to blood pressure in female twins.

It has been proposed that low birth weight is associated with high levels of blood pressure in later life. The aim of this study was to assess the relationship of blood pressure to birth weight and current body size during growth and adulthood. A total of 711 female multiple births, with one group of 244 in their growth phase mean age 12.0 (2.3)(SD) years and the other of 467 adults (mean age 35.2 (12.6) years), had height, weight and both systolic (SBP) and diastolic (DBP) blood pressures measured, and self-reported their birth weight. Regression analyses were performed to assess the cross-sectional and within-pair associations of blood pressure to birth weight, with and without adjustments for current body size. Within-pair analysis was based on 296 twin pairs. Cross-sectionally, a reduction in birth weight of 1 kg was associated with 2 to 3 mm Hg higher age-adjusted SBP, which was of marginal significance and explained about 2% of the population variance. Adjustment for body mass index did not significantly change this association. Within-pair analyses found no association between birth weight and SBP or DBP,even after adjusting for current body size. After age, current body size was the strongest predictor of systolic BP. The weak association of blood pressure to birth weight cross-sectionally is of interest, but any within-pair effect of birth weight on blood pressure must be minimal compared with the effect of current body size.     

Sex-specific effects of placental restriction on components of the metabolic syndrome in young adult sheep

Prenatal and early postnatal life experiences, reflected by size at birth and postnatal catch-up growth, contribute to the risk of developing the metabolic syndrome in adulthood, but their relative importance is unclear. Therefore, we determined the effects of restricted placental and fetal growth on components of the metabolic syndrome in young adult sheep and the relationships of the latter to size at birth and early postnatal growth. Fasting plasma metabolites, glucose tolerance (by intravenous glucose tolerance test, IVGTT), insulin secretion and sensitivity, and resting blood pressure were measured in 22 control and 20 placentally restricted (PR) 1-yr-old sheep. In male sheep, PR increased the initial rise in glucose during an IVGTT and reduced diastolic blood pressure, and small size at birth independently predicted reduced adult size, glucose tolerance, and fasting plasma insulin and insulin disposition of glucose metabolism but increased insulin disposition of circulating FFAs. Also in males, high fractional growth rates in early postnatal life independently predicted impaired early glucose clearance during an IVGTT. In female animals, PR increased insulin sensitivity of glucose metabolism and reduced fasting plasma FFAs, and thinness at birth predicted increased adult size, fasting blood glucose, and pulse pressure. In conclusion, PR and small size at birth are associated with more components of the metabolic syndrome in adult male than in adult female sheep, with few independent effects of early postnatal growth. These sex differences in the onset and extent of adverse metabolic consequences after prenatal restraint in the sheep are consistent with observations in humans.     

Hypertension and nutrition in the young: early intervention?

The few studies, carried out on infants, children, and adolescents, relating blood pressure to sodium intake have shown a weak positive correlation in some but not all individuals. The effect of body size on blood pressure confounds the interpretation of the effect of dietary sodium on blood pressure. There appear to be sodium-sensitive and sodium-unsensitive infants, children, and adolescents and is probably genetically transmitted. Most infants, children, and adolescents in industrialized populations have a salt intake far greater than required, and reduction in dietary sodium is safe and may be beneficial to those individuals with a family history of primary hypertension.     

THE ROLE OF GRAVITY IN THE EVOLUTION OF MAMMALIAN BLOOD PRESSURE

Understanding of the factors involved in determining the level of central arterial blood pressure in mammals has been clouded by inappropriate allometric analyses that fail to account for phylogenetic relationships among species, and require pressure to approach 0 as body size decreases. The present study analyses systolic, mean arterial, and diastolic blood pressure in 47 species of mammal with phylogenetically informed techniques applied to two‐parameter equations. It also sets nonlinear, three‐parameter equations to the data to remove the assumption of the two‐parameter power equation that the smallest animals must have negligible blood pressure. These analyses show that blood pressure increases with body size. Nonlinear analyses show that mean blood pressure increases from 93 mmHg in a 10 g mouse to 156 mmHg in a 4 tonne elephant. The scaling exponent of blood pressure is generally lower than, though not significantly different from, the exponent predicted on the basis of the expected scaling of the vertical distance between the head and the heart. This indicates that compensation for the vertical distance above the heart is not perfect and suggests that the pressure required to perfuse the capillaries at the top of the body may decrease in larger species.     

Factors affecting blood pressure during heavy weight lifting and static contractions.

Brachial arterial pressure was directly recorded in 31 healthy male volunteers through protocols examining the effects of the Valsalva maneuver, muscle size and strength, contraction force, contraction type (concentric, isometric, eccentric), changes in joint angle, and muscle fatigue on the blood pressure response to resistance exercise. Weight lifting at the same relative intensity produced similar increases in blood pressure, regardless of individual differences in muscle size or strength. Concentric, isometric, or eccentric exercise at the same relative intensity caused similar increases despite differences in force production. In weight lifting, the greatest increase in blood pressure occurred at the joint angle corresponding to the weakest point in the strength curve and the least at the angle corresponding to the strongest point. Isometric contractions of the same relative intensity at different joint angles produced identical blood pressures despite differences in absolute force production. When subjects attempted to maintain a maximum isometric contraction for 45 s, the blood pressure increase remained the same despite a marked diminution in force. Thus the magnitude of the blood pressure response depends on the degree of effort or central command and not actual force production. A brief Valsalva maneuver, which exaggerates the increase in blood pressure, is unavoidable when desired force production exceeds approximately 80% maximum voluntary contraction.     

Structural, functional and hypertensive effects of 19-oxo-11-deoxycorticosterone acetate (19-oxo-DOCA) in the rat

Mononephrectomized rats were given 1% NaCl solution to drink; half of them received 1 mg/day of 19-oxo-11 deoxycorticosterone acetate (19-oxo-DOCA) in sesame oil subcutaneously and half received only the oil for a period of four weeks. The steroid had no effect upon saline intake, systolic blood pressure, growth or the size of adrenals, hearts or kidneys, although it did produce hypernatremia and hypokalemia. The discrepancy between a demonstrable mineralocorticoid effect without blood pressure elevation awaits elucidation.     

Changes in oscillometric pulse amplitude envelope with cuff size: implications for blood pressure measurement criteria and cuff size selection

Oscillometric blood pressures are derived from the amplitude envelope of oscillometric pulses generated in an occlusive cuff during cuff inflation or deflation; one factor which will affect the characteristics of these pulses is the size of the cuff bladder. Because limiting values are stipulated in recommendations and standards for bladder sizes, there is a wide variety of acceptable cuff sizes for any particular application. An experimental and theoretical study was undertaken to show the dependence of oscillometric blood pressures on bladder size. Actual cuff-arm compliance data were obtained from two subjects for two cuffs of different bladder size. Theoretical analysis was then applied to the data to predict the effects of different bladder sizes on the characteristics of the pulses. The results show that cuff-arm compliance and bladder size interact to affect the pulse amplitude and hence oscillometric blood pressure determination. These results suggest that blood pressures obtained using the oscillometric method may vary depending on cuff size, and in particular that replacement cuffs for oscillometric non-invasive blood pressure monitors should be chosen carefully.     

The influence of basal metabolic rate on blood pressure among indigenous Siberians

Hypertension is an important global health issue and is currently increasing at a rapid pace in most industrializing nations. Although a number of risk factors have been linked with the development of hypertension, including obesity, high dietary sodium, and chronic psychosocial stress, these factors cannot fully explain the variation in blood pressure and hypertension rates that occurs within and between populations. The present study uses data collected on adults from three indigenous Siberian populations (Evenki, Buryat, and Yakut [Sakha]) to test the hypothesis of Luke et al. (Hypertension 43 (2004) 555-560) that basal metabolic rate (BMR) and blood pressure are positively associated independent of body size. When adjusted for body size and composition, as well as potentially confounding variables such as age, smoking status, ethnicity, and degree of urbanization, BMR was positively correlated with systolic blood pressure (SBP; P < 0.01) and pulse pressure (PP; P < 0.01); BMR showed a trend with diastolic blood pressure (DBP; P = 0.08). Thus, higher BMR is associated with higher SBP and PP; this is opposite the well-documented inverse relationship between physical activity and blood pressure. If the influence of BMR on blood pressure is confirmed, the systematically elevated BMRs of indigenous Siberians may help explain the relatively high blood pressures and hypertension rates documented among native Siberians in the post-Soviet period. These findings underscore the importance of considering the influence of biological adaptation to regional environmental conditions in structuring health changes associated with economic development and lifestyle change.     

Early influences on blood pressure: a study of children aged 5-7 years.

OBJECTIVE--To examine factors that influence blood pressure in children. DESIGN--Cross sectional study of children aged 5.0-7.0 years who had blood pressure measurements and for whom parental questionnaires were completed. SETTING--School based survey. SUBJECTS--3591 Children aged 5.0-7.5 years selected by stratified random sampling of primary schools in nine British towns (response rate 72%); 3591 were examined and their parental questionnaires were completed. Data were complete for birth rank in 3559, maternal age in 3542, maternal history of hypertension in 3524, and paternal history in 2633. RESULTS--Birth weight was inversely related to mean systolic blood pressure but only when standardised for current weight (weight standardised regression coefficient -1.83 mm Hg/kg (95% confidence interval -1.31 to -2.35). Mean diastolic pressure was similarly related to birth weight. Maternal age, birth rank, and a parental history of hypertension were all related to blood pressure. After standardisation for current weight a 10 year increase in maternal age was associated with a 1.0 mm Hg (0.4 to 1.6) rise in systolic pressure; first born children had systolic blood pressure on average 2.53 mm Hg (0.81 to 4.25) higher than those whose birth rank was greater than or equal to 4; and a maternal history of hypertension was associated with a systolic pressure on average 0.96 mm Hg (0.41 to 1.51) higher than in those with no such history. The effects described were largely independent of one another and of age and social class. The relation for birth rank was, however, closely related to that for family size. CONCLUSIONS--Influences acting in early life may be important determinants of blood pressure in the first decade. The relation between birth weight and blood pressure may reflect the rate of weight gain in infancy. The reasons for the relation with birth rank and maternal age are unknown; if confirmed they imply that delayed motherhood and smaller family size may be associated with higher blood pressure in offspring.     

Impact of Measurement Error on Testing Genetic Association with Quantitative Traits

Measurement error of a phenotypic trait reduces the power to detect genetic associations. We examined the impact of sample size, allele frequency and effect size in presence of measurement error for quantitative traits. The statistical power to detect genetic association with phenotype mean and variability was investigated analytically. The non-centrality parameter for a non-central F distribution was derived and verified using computer simulations. We obtained equivalent formulas for the cost of phenotype measurement error. Effects of differences in measurements were examined in a genome-wide association study (GWAS) of two grading scales for cataract and a replication study of genetic variants influencing blood pressure. The mean absolute difference between the analytic power and simulation power for comparison of phenotypic means and variances was less than 0.005, and the absolute difference did not exceed 0.02. To maintain the same power, a one standard deviation (SD) in measurement error of a standard normal distributed trait required a one-fold increase in sample size for comparison of means, and a three-fold increase in sample size for comparison of variances. GWAS results revealed almost no overlap in the significant SNPs (p<10⁻⁵) for the two cataract grading scales while replication results in genetic variants of blood pressure displayed no significant differences between averaged blood pressure measurements and single blood pressure measurements. We have developed a framework for researchers to quantify power in the presence of measurement error, which will be applicable to studies of phenotypes in which the measurement is highly variable.     

Decrease of myocardial infarct size with desferrioxamine: possible role of oxygen free radicals in its ameliorative effect

The ability of an iron chelator, desferrioxamine, to inhibit the infarct size in in vivo rat heart was assessed. Anaesthetised rats were subjected to coronary artery ligation (CAL) for 72 hr and infarct size was measured macroscopically using TTC staining. Systolic blood pressure and ECG were monitored. Desferrioxamine (10 mg/kg and 20 mg/kg i.v.) administered half an hour after CAL markedly reduced the infarct size. However, drug treatment did not alter the systolic blood pressure of animals. In addition, desferrioxamine in vitro and in vivo demonstrated an inhibition of rat PMN-evoked and luminol-enhanced chemiluminiscence. The capacity of desferrioxamine to impair the generation or to scavenge directly oxygen free radicals may be responsible for its beneficial effect on myocardial infarct size in rats.     

Mathematical modeling of the circulation in the liver lobule

In this paper, we develop a mathematical model of blood circulation in the liver lobule. We aim to find the pressure and flux distributions within a liver lobule. We also investigate the effects of changes in pressure that occur following a resection of part of the liver, which often leads to high pressure in the portal vein. The liver can be divided into functional units called lobules. Each lobule has a hexagonal cross-section, and we assume that its longitudinal extent is large compared with its width. We consider an infinite lattice of identical lobules and study the two-dimensional flow in the hexagonal cross-sections. We model the sinusoidal space as a porous medium, with blood entering from the portal tracts (located at each of the vertices of the cross-section of the lobule) and exiting via the centrilobular vein (located in the center of the cross-section). We first develop and solve an idealized mathematical model, treating the porous medium as rigid and isotropic and blood as a Newtonian fluid. The pressure drop across the lobule and the flux of blood through the lobule are proportional to one another. In spite of its simplicity, the model gives insight into the real pressure and velocity distribution in the lobule. We then consider three modifications of the model that are designed to make it more realistic. In the first modification, we account for the fact that the sinusoids tend to be preferentially aligned in the direction of the centrilobular vein by considering an anisotropic porous medium. In the second, we account more accurately for the true behavior of the blood by using a shear-thinning model. We show that both these modifications have a small quantitative effect on the behavior but no qualitative effect. The motivation for the final modification is to understand what happens either after a partial resection of the liver or after an implantation of a liver of small size. In these cases, the pressure is observed to rise significantly, which could cause deformation of the tissue. We show that including the effects of tissue compliance in the model means that the total blood flow increases more than linearly as the pressure rises.     

Role of beta-adrenergic agonists in the control of vascular capacitance

The role of beta-adrenergic agonists, such as isoproterenol, on vascular capacitance is unclear. Some investigators have suggested that isoproterenol causes a net transfer of blood to the chest from the splanchnic bed. We tested this hypothesis in dogs by measuring liver thickness, cardiac output, cardiopulmonary blood volume, mean circulatory filling pressure, portal venous, central venous, pulmonary arterial, and systemic arterial pressures while infusing norepinephrine (2.6 micrograms.min-1.kg-1), or isoproterenol (2.0 micrograms.min-1.kg-1), or histamine (4 micrograms.min-1.kg-1), or a combination of histamine and isoproterenol. Norepinephrine (an alpha- and beta 1-adrenergic agonist) decreased hepatic thickness and increased mean circulatory filling pressure, cardiac output, cardiopulmonary blood volume, total peripheral resistance, and systemic arterial and portal pressures. Isoproterenol increased cardiac output and decreased total peripheral resistance, but it had little effect on liver thickness or mean circulatory filling pressure and did not increase the cardiopulmonary blood volume or central venous pressure. Histamine caused a marked increase in portal pressure and liver thickness and decreased cardiac output, but it had little effect on the estimated mean circulatory filling pressure. Isoproterenol during histamine infusions reduced histamine-induced portal hypertension, reduced liver size, and increased cardiac output. We conclude that the beta-adrenergic agonist, isoproterenol, has little influence on vascular capacitance or liver volume of dogs, unless the hepatic outflow resistance is elevated by agents such as histamine.     

Associations of Blood Pressure with Body Composition among Afro-Caribbean Children in Barbados

Despite complex presentation of adult hypertension and a concomitant obesity epidemic, little is known about overweight in relation to blood pressure among Caribbean children. We examined blood pressure in relation to body size in a cross-sectional study of 573 Barbadian children aged 9–10 years (2010-2011).The United States normative blood pressure percentiles were used to identify children with high (≥ 95^th percentile) or high normal blood pressure (90^th – 95^th percentile). The World Health Organization body mass index cut-off points were used to assess weight status.

Major findings

Thirty percent of children were overweight/obese. Percentage fat mass differed between girls (20.4%) and boys (17.72%) (p< 0.05). Mean systolic blood pressure among girls was 106.11 (95% CI 105.05, 107.17) mmHg and 105.23 (104.09, 106.38) for boys. The percentages with high or high-normal mean systolic blood pressurewere14.38% (10.47, 18.29) for girls and 8.08% (4.74, 11.41) for boys. Height and body mass index were independent correlates of systolic and diastolic blood pressure. Mean systolic blood pressure was related to lean mass but not fat mass, while diastolic blood pressure was associated with fat mass index and overweight.

Principal conclusion

One third of 9-10 year old children in Barbados were overweight/obese and 12% had elevated mean systolic blood pressure. BP was related to body size. These findings signal potential adverse trends in weight gain and BP trends for children growing up in the context of a country that has recently undergone rapid economic transition.     

Allometric scaling of mammalian blood pressure: A comment on White and Seymour (2014)

White and Seymour examined the scaling of central arterial blood pressure against body mass in mammals ranging in size from a 30 g mouse to a 4080 kg elephant. Exponents in power functions fitted to each of three datasets (systolic, diastolic, and mean arterial pressure) were reported to be significantly greater than zero and indistinguishable from 0.33. The first of these outcomes would indicate that blood pressure increases with body size, whereas the second is consistent with the heart working against gravity to move blood to the head. Taken together, these results seemingly refute the notion that the cephalic circulation functions as an energy‐neutral siphon. However, the main findings by White and Seymour were presented in the form of graphs that distorted the relationships between the variables of interest. I use simple graphics to show that the data were unsuited from the outset for use in allometric analyses and that conclusions of the investigation are not well supported.     

Accurate,reproducible measurement of blood pressure.

The diagnosis of mild hypertension and the treatment of hypertension require accurate measurement of blood pressure. Blood pressure readings are altered by various factors that influence the patient, the techniques used and the accuracy of the sphygmomanometer. The variability of readings can be reduced if informed patients prepare in advance by emptying their bladder and bowel, by avoiding over-the-counter vasoactive drugs the day of measurement and by avoiding exposure to cold, caffeine consumption, smoking and physical exertion within half an hour before measurement. The use of standardized techniques to measure blood pressure will help to avoid large systematic errors. Poor technique can account for differences in readings of more than 15 mm Hg and ultimately misdiagnosis. Most of the recommended procedures are simple and, when routinely incorporated into clinical practice, require little additional time. The equipment must be appropriate and in good condition. Physicians should have a suitable selection of cuff sizes readily available; the use of the correct cuff size is essential to minimize systematic errors in blood pressure measurement. Semiannual calibration of aneroid sphygmomanometers and annual inspection of mercury sphygmomanometers and blood pressure cuffs are recommended. We review the methods recommended for measuring blood pressure and discuss the factors known to produce large differences in blood pressure readings.     

Relationship of body size and body mass to blood pressure: sex-specific and developmental influences.

The relationship of body mass and body fat distribution to blood pressure has been recognized for many years. This relationship has formed the basis for much additional research, including the impact of growth and developmental factors on blood pressure levels. Blood pressure in children is related to somatic growth and is tied to increases in height, skeletal maturation, and sexual maturation. Sexual and ethnic differences in blood pressure levels are already apparent during childhood and may also be related to the process of growth and sexual maturity. Body size exerts a profound influence on a variety of physiological functions, including blood pressure and the onset of sexual maturity. In general, studies have reported a strong linear relationship between height and blood pressure and between body mass and blood pressure such that tracking correlations from childhood to adulthood for both blood pressure and body mass index are significant for most sex and ethnic groups. Studies evaluating the effects of hormone replacement therapy on post-menopausal women have thus far generated results suggesting that the age-related rise of blood pressure is not due directly to hormonal changes associated with menopause. The interrelated effects of growth, maturation, body weight, and body fat are influenced by both genetic and environmental factors. Environmental influences may modify relationships established much earlier, perhaps as early as prenatally, during infancy, or during early childhood. Directions for future research and implications resulting from the complex relationship between body weight and blood pressure are discussed.     

Some observatoons on the carotid bodies of the New Zealand strain of genetically hypertensive rats

We report preliminary studies of the carotid bodies in the New Zealand strain of hypertensive rats. Female animals have a higher blood pressure than males of the same colony, but in both sexes mean arterial pressure is elevated significantly when compared to normal animals. The carotid bodies are enlarged in both the hypertensive and normotensive animals and there is no correlation between carotid body size and arterial pressure. The only structural abnormality detected in the hypertensive carotid bodies was a gross thickening of the intimal layer of the arterioles. The content of dopamine in the organs was similar in normotensives and hypertensives but the noradrenaline levels were some 50% lower in the hypotensives. These results are discussed and compared with data available for SHR animals.