Aging accelerates dietary lard-induced increase in blood pressure in rats

We investigated whether the dietary lard-induced increase in blood pressure (BP) is accelerated in aged rats compared to young ones. Three-month-old (young group), 10-month-old (middle-age group), and 18-month-old (older group) F344/N male rats were used. The rats were fed either chow alone or chow in which 50% of the energy content was from substituted lard. Systolic BP (SBP) and body weights (BW) were determined weekly during each 7-week feeding period. A Steady-state plasma glucose (SSPG) method was used to determine the insulin sensitivity. Bilateral testicular fat mass (epididymal fat; Epi-F) was removed in order to evaluate weight (Epi-FW). SBP began to increase at 2 weeks in the older lard-fed group, at 4 weeks in the middle-age lard-fed group, and at 5 weeks in the young lard-fed group after feeding was begun. There was no significant difference in the basal values of SBP among any ages-groups of the rats. After 4 weeks of lard feeding, increases in SBP, plasma insulin, leptin level, SSPG and Epi-FW/BW were observed in the older lard-fed group. In the younger rats, however, only hyperinsulinemia developed. At 7 weeks, increased BP in the younger rats was accompanied by increased plasma leptin level, SSPG and Epi-FW/BW. In summary, aging accelerates development of a dietary lard-induced increase in BP, which may be caused by the hyperleptinemia that may be the result of increased susceptibility to insulin resistance and/or visceral adiposity in older rats.     

Gender differences in the regulation of blood pressure

Men are at greater risk for cardiovascular and renal disease than are age-matched, premenopausal women. Recent studies using the technique of 24-hour ambulatory blood pressure monitoring have shown that blood pressure is higher in men than in women at similar ages. After menopause, however, blood pressure increases in women to levels even higher than in men. Hormone replacement therapy in most cases does not significantly reduce blood pressure in postmenopausal women, suggesting that the loss of estrogens may not be the only component involved in the higher blood pressure in women after menopause. In contrast, androgens may decrease only slightly, if at all, in postmenopausal women. In this review the possible mechanisms by which androgens may increase blood pressure are discussed. Findings in animal studies show that there is a blunting of the pressure-natriuresis relationship in male spontaneously hypertensive rats and in ovariectomized female spontaneously hypertensive rats treated chronically with testosterone. The key factor in controlling the pressure-natriuresis relationship is the renin-angiotensin system (RAS). The possibility that androgens increase blood pressure via the RAS is explored, and the possibility that the RAS also promotes oxidative stress leading to production of vasoconstrictor substances and reduction in nitric oxide availability is proposed.     

Gender differences in the relation between number of teeth and systolic blood pressure

BACKGROUND: Tooth loss predicts total and circulatory mortality. The reasons for the increased mortality in subjects with a low number of teeth may be related to enhanced atherosclerosis, elevated arterial pressure and more frequent hypertension. The present study was designed to investigate whether there is an association between the number of teeth and arterial pressure or hypertension. METHODS: We used data of 4185 adult subjects (2150 women) collected for the population-based Study of Health in Pomerania. The number of teeth was counted by trained and certified dentists. Hypertension was defined as systolic blood pressure >or= 140 mmHg or diastolic blood pressure >or= 90 mmHg or use of antihypertensive medication. Multivariable analyses were adjusted for relevant confounders. RESULTS: The adjusted mean (standard error) systolic blood pressure in men having 0-6 teeth was 149.6 mmHg (1.3 mmHg) compared to 142.6 mmHg (1.2 mmHg) in men having 27-28 teeth (P < 0.05). The adjusted odds for hypertension in men with 0-6 teeth compared to men with 27-28 teeth were 1.91 (95% confidence interval 1.21; 3.02, P < 0.05). In women no such relations were found. CONCLUSION: There is an inverse association between the number of teeth and systolic blood pressure and hypertension in men but not in women. The present findings partly explain the relation between tooth loss and mortality.     

Acetylsalicylic acid mitigates erythropoietin-associated blood pressure increase in nonuremic rats

Abstract

Background: Approximately 30% of the chronic kidney disease patients using recombinant human erythropoietin (rhuEPO) have an increase in blood pressure (BP). Its mechanism and whether it depends on renal function remain unclear. There is early evidence that acetylsalicylic acid (ASA) prevents the rhuEPO-induced increase in BP. This study aims to verify whether very high doses of rhuEPO can increase BP in nonuremic rats and whether the co-administration of ASA can prevent it. Methods: Forty male Wistar rats were divided into four groups: placebo/placebo; placebo/rhuEPO 200?UI/kg thrice weekly; placebo/ASA 50?mg/kg daily; rhuEPO 200?UI/kg thrice weekly/ASA 50?mg/kg daily. Hematocrit was measured before and after and systolic BP was measured weekly by tail-cuff technique. Direct measurement of the BP was obtained at the end. Results: The rhuEPO groups had higher final hematocrit (rhuEPO/placebo 56.7?±?7.6, rhuEPO/ASA 56.7?±?7.7; p?<?0.001 versus placebo/placebo, 42.2?±?4.7 and ASA/placebo 41.2?±?4.2); and also increase in systolic BP (rhuEPO/placebo 135.1?±?15.0, p?=?0.01 and rhuEPO/ASA 127.2?±?6.8, p?=?0.02), whereas BP in rats from placebo/placebo (120.9?±?5.0, p?=?0.18) and placebo/ASA (124.6?±?13.3, p?=?0.12) groups remained unchanged. By direct measurement, the final BP was higher in rhuEPO/placebo (DBP 123.1?±?12.0; SBP 157.4?±?12.5; MBP 139.8?±?11.9) than placebo/placebo (DBP 105.1?±?11.5; SBP 141.0?±?12.6; MBP 122.1?±?12.1) and placebo/ASA groups (DBP 106.6?±?8.1; SBP 141.5?±?8.4, MBP 122.1?±?7.2) (p?<?0.05 by post hoc Bonferroni test ANOVA). The rhuEPO/ASA group (PAD 115.1?±?11.4, PAS 147.4?±?9.1, MBP 130.1?±?10.3) was not different from other groups. Conclusions: The administration of very high doses of rhuEPO is associated with an increase in hematocrit and BP in nonuremic rats. The concomitant use of ASA mitigates the rhuEPO-associated BP increase.     

Dietary fat-induced increase in blood pressure and insulin resistance in rats

OBJECTIVES: To determine whether the dietary-fat-induced increase in blood pressure is caused by excess energy intake or the fat composition of the diet, what type of fat increases the blood pressure, and whether insulin resistance is involved in the dietary-fat-induced increase in blood pressure. METHODS: In a series of experiments, rats received: chow alone or chow supplemented with lard or sucrose to provide 33% of a total energy content increased by 50%; chow alone or chow in which 50% of the energy content was from substituted lard, safflower oil or medium-chain triglyceride oil; or chow alone or chow in which 50% of the energy content was from substituted lard, with or without troglitazone. Systolic blood pressure (SBP) was measured every week during each 8-week feeding period. A steady-state serum glucose method was used to determine the insulin sensitivity after the lard substitution with or without troglitazone. RESULTS: Both the lard and sucrose enrichment increased SBP and body weight compared with controls. Lard substitution significantly increased SBP and immunoreactive insulin, although body weight did not differ from control. Neither a diet substituted with safflower oil nor one substituted with medium-chain triglyceride oil influenced SBP. Troglitazone completely inhibited the increase in SBP and immunoreactive insulin induced by the lard. The steady-state serum glucose concentration was significantly greater after the lard substitution than after isoenergetic chow; this effect also was reversed by troglitazone. CONCLUSION: Chronic feeding with lard increased SBP in rats, independently of excess energy intake. Of the fats tested, lard exerted an intrinsic pressor effect. Troglitazone reversed the lard-induced increase in SBP.     

Gender and blood pressure

The prevalence, impact, and control of hypertension differ between the sexes in the US population. In addition, pregnancy, oral contraceptive use, and menopausal hormone therapy may influence blood pressure regulation in ways that have therapeutic implications for some women. Whether gender should be a significant consideration in the choice of individual antihypertensive drugs continues to be a topic of intense interest and debate. This brief review will discuss recent findings that bear on considerations of gender in the management of hypertension, particularly among older women.     

Sex differences in blood pressure response to intermittent hypoxia in rats

Intermittent hypoxia is used to mimic the arterial hypoxemia that occurs during sleep apnea. The present study examined the blood pressure and heart rate responses to exposure to intermittent hypoxia in male rats and in female rats before and after ovariectomy. Rats were instrumented with telemetry transmitters and blood pressure, heart rate, and activity measured during 7 days of exposure to intermittent hypoxia (3 minutes of normoxia [21% oxygen] alternating with 3 minutes 10% oxygen between 8 am and 4 pm, remainder of day at normoxia). Blood pressure increased in males, females, and ovariectomized females in response to 7 days of intermittent hypoxia during the hours of exposure to hypoxia. Blood pressure increased less in intact females (average change in blood pressure 1.6+/-0.6 mm Hg, n=11) than in females studied after ovariectomy (5.1+/-1.1 mm Hg, n=6) or males (5.4+/-1.0 mm Hg, n=10). This elevated blood pressure persisted throughout the remainder of the day when the animals were not exposed to intermittent hypoxia and remained significantly attenuated in female rats. Ovariectomy abolished the protection against the elevated blood pressure response to intermittent hypoxia in females. Heart rate increased only in males, and only during the period of the day associated with intermittent hypoxia. Female rats were protected against this tachycardia independent of the ovarian hormones. These results indicate that females are protected from the hypertensive and tachycardia effects of intermittent hypoxia.     

Gender differences in the association between anthropometric indices of obesity and blood pressure in Japanese.

To investigate which of four anthropometric variables of obesity has the strongest association with blood pressure (BP), and to investigate whether there are gender differences in these relationships in Asian adults, we evaluated the associations of four anthropometric variables, body mass index (BMI), waist circumference, waist-to-hip ratio and waist-to-height ratio, with BP and the prevalence of hypertension in a cross-sectional study. A total of 4,557 employees of a metal-products factory in Toyama, Japan (2,935 men and 1,622 women, aged 35 to 59 years) were included in the study. Waist circumference in men and BMI in women had the strongest associations with BP. As for the age-adjusted rate ratio (RR) of the prevalence of hypertension for one standard deviation increase in each anthropometric variable, RR was the highest for waist circumference in men (RR, 1.44; 95% confidence interval [CI], 1.31-1.58), and for BMI in women (RR, 1.61; 95% CI, 1.38-1.88). The associations of waist circumference in men and BMI in women remained significant after adjustment for each of the other variables. The associations of waist-to-height ratio with BP and the prevalence of hypertension were a little weaker than those of waist circumference for both men and women. In conclusion, among four anthropometric variables of obesity--i.e., BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio-waist circumference had the strongest association with BP and the prevalence of hypertension in men and BMI had the strongest association with BP and hypertension in women. Waist circumference in men and BMI in women should be given more importance in the screening of and guidelines on hypertension in Asians.     

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

The incidence of obesity has increased enormously in the past several decades, and has been described as a modern epidemic. Obesity is a major factor contributing to hypertension. To the best of our knowledge, no study of ambulatory blood pressure monitoring (ABPM) comparing men with women in relation to body mass indexes (BMI) has been performed. From December 2002 to May 2006, we performed 24-h ABPM in 5950 subjects (3102 men and 2848 women), with a wide range of BMI (range 15.9-53.2 kg/m(2)). We defined obese subjects as those with BMI> or =30.0 kg/m(2), overweight subjects as those with BMI>25.0 and <30.0 kg/m(2), and normal subjects as those with BMI< or =25.0 kg/m(2). Data on 989 subjects (501 men and 488 women) aged from > or =18 to < or =69 years without antihypertensive treatment, atrial fibrillation or diabetes were included for analysis. We consistently found that obese men had the expected increased heart rate compared to normal and overweight men, whereas women (normal, overweight and obese) had similar HRs. In addition, normal and obese women had similar diastolic blood pressures (BP), as opposed to obese men, who had raised diastolic BP. These results may indicate that different pathogenetic mechanisms may be involved in the relationship between obesity and hypertension in men and women.     

Gender differences in antacid-induced phosphate deprivation in rats

To determine whether an animal model could be used to study the susceptibility of women to antacid-induced phosphate deficiency, 6-wk-old male and female rats were given basic aluminum carbonate gel (Basaljel) (1 ml/100 g body wt) or distilled water by gastric intubation daily for 3 wk. Rats were fed either ad libitum (group 1) or by pair-feeding (group 2) with pelleted rat food containing 0.74% phosphorus. In group 1, baseline, 1-wk, and 3-wk values for serum phosphorus in Basaljel-treated females were 7.7 +/- 0.2, 6.3 +/- 0.2, and 6.2 +/- 0.2 mg/dl, respectively. Corresponding values for control females were 7.8 +/- 0.3, 7.0 +/- 0.2, and 7.3 +/- 0.2 mg/dl. Values for treated females were significantly lower (p less than 0.02) than values for control females by 1 wk of treatment. Basaljel-treated males did not differ from controls. The pattern for group 2 was similar. Intestinal absorption and intramuscular stores of phosphate were assessed in group 1. After 3 wk of treatment, [32P]phosphate assimilation from the duodenum into the body was lower in Basaljel-treated females than in controls (33.8% +/- 1.9% vs. 49.8% +/- 6.2% of the luminally administered dose, p less than 0.05). This was due to increased retention of [32P]phosphate in the intestine of treated females (19.9% +/- 2.0% vs. 11.9% +/- 2.4% for control females, p less than 0.02). Results in jejunum were similar. Total intramuscular phosphate in females was significantly lower (p less than 0.005) than in males both before and after antacid treatment. Thus hypophosphatemia in the female rat during antacid administration is probably secondary to the additive effects of decreased assimilation and decreased soft tissue stores of phosphate.     

Sex differences in casual and ambulatory blood pressure responses to extreme changes in dietary sodium

OBJECTIVE: To compare the awake ambulatory and seated casual blood pressure responses to extreme changes in dietary sodium during a 4-month period between borderline hypertensive men (n = 24, aged 51+/- 7 years) and women (n = 8, aged 47+/- 8 years). METHODS: Seated casual and awake ambulatory (over an average of 9 h, n = 32 readings) blood pressures were recorded at the end of 1-month trials of low (24 +/- mmol/day for men, 32 +/- 19 mmol/day for women) and high (330 +/- 101 mmol/day for men, 298 +/- 76 for women) intakes of dietary sodium. There was a 1-month interim period between the two trial periods and energy and potassium intake were maintained constant over the entire course of the study. RESULTS: Among men, there was a similar average increase in blood pressure on going from the low- to the high-sodium diets according to the two methods of measurement, but among women there was a significant difference between the methods, such that the change in ambulatory blood pressure was less than the change in casual blood pressure. Women's casual blood pressure increased by 14/7 mmHg more than did their ambulatory blood pressure, whereas men's ambulatory blood pressure increased by 5/2 mmHg more than did their casual blood pressure (sex difference P < 0.009 for systolic and P < 0.037 for diastolic blood pressures). Finally, there was at best only modest concordance between changes in casual and ambulatory blood pressures between diets in individual patients, regardless of their sex, although men were more likely to have similar changes in their casual and ambulatory measurements than were women. CONCLUSION: The determination of the sensitivity of blood pressure to dietary sodium intake may depend upon how blood pressure is measured. There may also be an interaction between sex and blood pressure measurement technique that could affect the determination of salt-sensitivity differences between men and women.     

Gender differences in blood levels, but not brain levels, of ethanol in rats

Female rodents tend to drink more alcohol than males, a difference that emerges at puberty and appears to vary over the female estrous cycle. In addition, male and female rodents display different responses to alcohol; for example, female rats are reported to have faster elimination rates than males. We were interested in whether circulating ovarian hormones influence alcohol distribution to or elimination from the brain of rats, which might explain observed differences in drinking behavior. We administered 0.8 g/kg of ethanol via intraperitoneal injection to age-matched male and female Sprague-Dawley rats. Extracellular brain ethanol was sampled using microdialysis, and vascular ethanol concentrations were determined via tail blood collection, in two separate experiments. Ethanol pharmacokinetic parameters were calculated for both compartments. There were no differences in pharmacokinetic parameters due to gender or estrous cycle stage in brain ethanol concentration profiles. There were, however, differences in blood ethanol profiles: females showed faster elimination rates and a smaller area under the ethanol concentration versus time curve than males. In addition, the maximum concentration varied significantly across the estrous cycle. These results suggest that (1) circulating ovarian hormones do not influence alcohol distribution to the brain, but do influence distribution to more peripheral tissues such as the tail; and (2) apparent differences in tail blood alcohol levels may not reflect differences in brain levels.     

Role of oxidative stress in the sex differences in blood pressure in spontaneously hypertensive rats

OBJECTIVE: The hypothesis was tested that differences in oxidative stress play a role in the sex differences in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male and female SHR [and Wistar-Kyoto (WKY) rats in the long-term study] (n = 6-12 per group) received tempol (30 mg/kg per day) or tap water for 6 weeks from 9 to 15 weeks of age or from birth until 15 weeks of age. Blood pressure [mean arterial pressure (MAP)] and kidney tissue F2-isoprostane (IsoP) were measured at 15 weeks of age. RESULTS: In SHR given tempol for 6 weeks, blood pressure and IsoP were reduced in males, but not in females. In SHR given tempol from birth, MAP was higher in SHR than WKY rats (SHR males, 181 +/- 2 mmHg; SHR females, 172 +/- 3 mmHg; WKY males, 100 +/- 2 mmHg; WKY females, 101 +/- 2 mmHg, P < 0.01), and tempol reduced MAP by 14% (156 +/- 3) and 26% (127 +/- 4) in male and female SHR, respectively, but had no effect on WKY rats. IsoP was higher in SHR than WKY rats and higher in male SHR than female SHR (SHR males, 5.18 +/- 0.23 ng/mg; SHR females, 3.71 +/- 0.19 ng/mg, P < 0.01; WKY males, 1.72 +/- 0.45 ng/mg; WKY females, 2.21 +/- 0.08 ng/mg, P < 0.05, compared with SHR). Tempol reduced IsoP in SHR to levels found in WKY rats, but had no effect on IsoP in WKY rats. CONCLUSIONS: Development of hypertension in SHR is mediated in part by oxidative stress independent of sex. Also, tempol is effective in reducing blood pressure in females only when given prior to the onset of hypertension.     

High magnesium diets increase blood pressure and enhance stroke mortality in hypertensive SHRsp rats

The effect of varying amounts of dietary magnesium in conjunction with potassium (K) on hypertension and stroke mortality in hypertensive stroke prone (SHRsp) rats was studied. These results show that high K (2.1%) diets strongly protect against stroke mortality and rises of blood pressure, while high magnesium (Mg) (0.26%) diets appeared to increase stroke mortality and accelerate the rise of blood pressure in SHRsp rats. Similarly, medium-high (1.3%) levels of K in the diet significantly reduced blood pressure and stroke mortality but not nearly as much as the 2.1% K in the high K diet.     

Cold acclimation-induced increase of systolic blood pressure in rats is associated with volume expansion

To investigate the mechanisms of cold-induced hypertension, the systolic blood pressure (SBP) and average daily water consumption were measured weekly in 6-month-old male Wistar rats; they were subsequently acclimated to thermoneutrality (26°C for 7 weeks), to cold temperature (6°C for 9 weeks), and then again reacclimated to 26°C for 5 weeks. Circulating plasma volume and whole blood viscosity were measured in subgroups of rats at the end of acclimation to 26°C after 2 days, after 1, 6, and 8 weeks of cold, and after 2 and 5 weeks of rewarming. The control values obtained at the end of thermoneutral period were: SBP = 130.8 ±18.6 mm Hg, plasma volume = 41.9 ± 4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 ± 0.48 cps, and daily water consumption = 42.25 ± 16.81 mL. After 48 h of cold exposure there was almost a 50% increase in plasma volume that persisted to a lesser degree throughout the whole period of cold exposure (P < .05). After 2 weeks of cold exposure the daily water consumption increased and SBP began to increase. After 6 weeks of cold exposure the SBP was 30 mm Hg above that of the control level (P < .001) and was accompanied by a 25% increase in whole blood viscosity (P < .05). At the end of 8 weeks of cold exposure the plasma volume was 56.8 ± 9.51 mL/kg and the whole blood viscosity was 8.0 ± 1.79 cps at the 22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SBP and increased whole blood viscosity persisted, whereas the increased daily water consumption and expanded plasma volume returned to normal. Therefore, the acclimation to cold is accompanied by the development of a volume-associated hypertension, which is sustained after rewarming without volume expansion.