Abnormalities of Anthropometric,Hemodynamic, and Autonomic Variables in Offspring of Hypertensive Parents

Young adult offspring of hypertensive parents (pHTN⊕) are a good model for assessing abnormalities of anthropometric, cardiometabolic, and autonomic variables prior to clinical hypertension. The objectives of this study were to determine whether these variables and autonomic responses to oral carbohydrates were altered in offspring of pHTN⊕. Two hundred consecutive patients, including 100 pHTN⊕, were evaluated, with 29 patients, including 14 pHTN⊕, given a 70‐gram carbohydrate load. The pHTN⊕ group had higher blood pressure, pulse pressure, abdominal circumference (AC), weight, body mass index, and basal metabolic rate than offspring of normotensive parents (pHTN∅). At baseline, the low‐frequency (LF, sympathetic) to high‐frequency (HF, parasympathetic) ratio, assessed by spectral analysis of heart rate variability, was similar in both groups. After the carbohydrate load, the LF/HF ratio was greater in offspring of pHTN⊕. pHTN⊕ individuals have abnormalities of anthropometric and hemodynamic variables at baseline and autonomic responses to oral carbohydrates before developing hypertension.

Hypertension is associated with a large and growing health and economic burden of cardiovascular and renal diseases.¹, ² High arterial pressure causes target organ changes in the brain, heart, vessels, and kidneys. The etiology of arterial hypertension is unknown in most cases, although genetic factors play an important role.³ Environmental and behavioral factors also participate and include excessive salt and alcohol intake, stress, smoking, sedentary lifestyle, and obesity. Obesity is commonly associated with hypertension and appears to begin early in offspring of hypertensive parents (pHTN⊕).⁴, ⁵ The offspring of pHTN⊕ are more likely to develop hypertension than those of normotensive parents (pHTN∅).⁴ Normotensive offspring of pHTN⊕ have higher casual arterial pressure than normotensive offspring of pHTN∅.⁴ The difference in arterial pressure between children of pHTN∅ and children of pHTN⊕ has been reported in infancy, childhood, adolescence, and adulthood.⁶ Anthropometric data such as body mass index (BMI), waist circumference, and neck circumference might be related to the pathogenesis of hypertension in the offspring of pHTN⊕. However, there is no consensus regarding this issue.⁷, ⁸, ⁹ The interrelation between offspring of pHTN⊕ and both anthropometric and environmental variables can result in increased blood pressure (BP) in patients with familial predisposition, ie, gene‐environment interactions.¹⁰ Although associations between hypertension and anthropometric, metabolic, and autonomic nervous system variables were reported,¹¹, ¹², ¹³ few studies have addressed this association in offspring of pHTN⊕ parents.The sympathetic nervous system plays an important role in the pathogenesis of arterial hypertension. Greater activity of the sympathetic nervous system leads to lower heart rate variability (HRV) and higher risk for cardiovascular events, such as myocardial infarction and sudden death.¹⁴, ¹⁵ Conversely, higher parasympathetic nervous system activity increases HRV and is associated with lower heart‐related mortality. Autonomic nervous system regulation in hypertensive patients appears to be altered, and the changes can be detected through spectral analysis.¹⁵ Autonomic nervous system changes can be affected by environmental factors including food intake, and may be modulated by family history. Inappropriate increase in sympathetic activity after any kind of challenge in normotensive patients could be indicative of autonomic imbalance preceding the onset of hypertension. In one report, normotensive offspring of pHTN⊕ show increased sympathetic activity at baseline and after isometric exercise.¹⁶ Carbohydrate consumption can have a negative effect on sympathetic activity in hypertensive patients.¹⁷ However, the impact of carbohydrate ingestion on autonomic balance has not been reported in normotensive offspring of pHTN⊕.The aim of this study was to assess anthropometric, hemodynamic, and metabolic variables, including basal metabolic rate, in pHTN⊕ and pHTN∅ offspring prior to the onset of hypertension. In a subset of pHTN⊕ and pHTN∅ offspring, autonomic function was assessed under fasting conditions and following an oral carbohydrate load.     

内皮素-1基因5'非翻译区多态性与体位性低血压相关性研究

目的探讨内皮素-1基因5’非翻译区一个功能性多态+138A/-与体位性低血压的关系。方法运用聚合酶链反应和限制性内切酶片段长度多态性方法分析381例未治疗高血压患者和291例血压正常者的内皮素-1基因+138A/-基因多态性。所有入选者均进行卧立位血压测量。结果高血压人群中体位性低血压患者与非体位性低血压组比较,内皮素-1基因+138A/-基因型和A等位基因频率差异无显著意义(14.7%vs.15.3%,P0.05)。正常血压人群中得到相似的结果(13.9%vs.15.7%,P0.05)。校正年龄、体重指数、卧位血压等因素后,高血压人群和正常人群中+138A/-各基因型间收缩压和舒张压体位性变化均无显著差异。结论在高血压人群和正常血压人群中均未发现内皮素-1基因+138A/-多态性与体位性低血压存在相关性的证据。     

A Single Exposure to Acrolein Desensitizes Baroreflex Responsiveness and Increases Cardiac Arrhythmias in Normotensive and Hypertensive Rats

Short-term exposure to air pollutants has been linked to acute cardiovascular morbidity and mortality. Even in the absence of overt signs or symptoms, pollutants can cause subtle disruptions to internal compensatory mechanisms, which maintain homeostatic balance in response to various environmental and physiological stressors. We hypothesized that a single exposure to acrolein, a ubiquitous gaseous air pollutant, would decrease the sensitivity of baroreflex (BRS), which maintains blood pressure by altering heart rate (HR), modify cardiac electrophysiological properties and increase arrhythmia in rats. Wistar–Kyoto normotensive (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters and a chronic jugular vein catheter were tested for BRS using phenylephrine and sodium nitroprusside 2 days before and 1 h after whole-body exposure to 3 ppm acrolein (3 h). HR and electrocardiogram (ECG) were continuously monitored for the detection of arrhythmia in the pre-exposure, exposure and post-exposure periods. Whole-body plethysmography was used to continuously monitor ventilation in conscious animals. SH rats had higher blood pressure, lower BRS and increased frequency of AV block as evidence by non-conducted p-waves when compared with WKY rats. A single exposure to acrolein caused a decrease in BRS and increased incidence of arrhythmia in both WKY and SH rats. There were minimal ECG differences between the strains, whereas only SH rats experienced irregular breathing during acrolein. These results demonstrate that acrolein causes immediate cardiovascular reflexive dysfunction and persistent arrhythmia in both normal and hypertensive animals. As such, homeostatic imbalance may be one mechanism by which air pollution increases risk 24 h after exposure, particularly in people with underlying cardiovascular disease.     

The Bergen Blood Pressure Study: Sodium Intake and Ambulatory Blood Pressure in Offspring of Hypertensive and Normotensive Families

Sodium intake, estimated by the 24-h urine sodium excretion, was assessed in 39 offspring of hypertensive families and 37 offspring of normotensive families. The family history of hypertension or normotension was defined according to parental BP data from two surveys conducted 27 years apart. Urine sodium excretion was similar in offspring of hypertensive and normotensive families, averaging 136 and 137 mmol/24 h, respectively. Monitored by non-invasive methodology in the urine sampling period, the average 24-h ambulatory blood pressure (BP) was approximately 10/10 mmHg higher in offspring of hypertensive than normotensive families. The clinically and statistically significant differences in BP between groups could not be explained by differences in sodium intake. After adjustment for confounding variables, the BP was not associated with the sodium excretion in the material as a whole or in either offspring group.     

Effects of Psychological and Physical Covariates on Plasma Catecholamines in Borderline Hypertensives and Offspring of Hypertensive Parents

The interpretation of plasma catecholamine measurements may be influenced by psychological and physical factors. Therefore, catecholamine concentrations were adjusted for between-subject differences by the following possible confounding factors, i.e. body-mass index, individual maximal physical work capacity, urinary sodium excretion rates and anxiety score. Subjects were 24 borderline essential hypertensives, aged 18–24 years, 50 age-matched normotensive offspring of hypertensive parents and 49 controls with no family history of hypertension studied at rest and during mental stressors (Stroop colour-word conflict test, mental arithmetic). Borderline hypertensives had consistently higher adjusted venous noradrenaline concentrations than control subjects (p<0.05). Adjusted plasma adrenaline concentrations were higher in borderline hypertensive subjects than in offspring of hypertensive parents during supine rest. Despite its limitations, venous plasma noradrenaline concentrations when adjusted for work capacity, body-mass, sodium excretion and anxiety suggest enhanced sympatho-neural activity in young borderline essential hypertensives.     

Endothelin-1 Induces CXCL1 and CXCL8 Secretion in Human Melanoma Cells

The endothelin pathway plays a critical role in melanoma tumor progression by a variety of mechanisms that enhance tumor cell growth, invasion, and metastasis. Here, we investigate the effect of this pathway on CXC chemokine expression in human melanoma cells and melanocytes. As determined by ELISA, endothelin-1 (ET-1) induces CXCL1 and CXCL8 secretion in three human melanoma cell lines in a concentration-dependent fashion. These responses are mediated by the endothelin-B receptor and are sustained over a 40 h time course. ET-1 does not induce CXCL1 secretion in primary human melanocytes but ET-3, an endothelin isoform, induces a low level of CXCL1 secretion in certain cultures. Neither ET-1 nor ET-3 induces secretion of CXCL8 in primary human melanocytes; thus, this response may be specific for melanocytic cells that have undergone malignant transformation. We have previously demonstrated that ET-1 induces changes in the expression of adhesion molecules in melanoma cells such that invasion and metastasis are favored. This study demonstrates that ET-1 additionally induces secretion of CXC chemokines critical for melanoma metastasis and tumor progression.     

Salt Preferences of Normotensive and Hypertensive Older Individuals

The aim of this study was to evaluate the preference for salt in hypertensive and normotensive older individuals. Hypertensive (group 1: n=32, aged 73.7±6.3 years) or normotensive patients (group 2: n=26, aged 71.5±8.0 years) were submitted to a test to determine their preference for bread samples with different salt concentrations: 1.5%, 2.0% (usual concentration), and 2.7%, and were reevaluated 2 weeks later using the same salt concentrations, but with the addition of oregano. Twenty‐four–hour urinary sodium excretion (UNaV), blood pressure (BP), and body mass index (BMI) were obtained. Systolic BP, BMI, and UNaV were higher in group 1. In the first analysis, group 1 showed greater preference for the saltiest sample (P=.001). Comparing the first evaluation and the second, a greater preference for less salty samples was observed in both groups (P<.01). Hypertensive older patients consumed more salt and showed a greater salt preference than the normotensive patients. The use of the spice reduced the preference for salt in both groups.     

Venous Volume in Offspring of Hypertensive Patients

Abstract Twenty normotensive healthy male offspring of hypertensive patients were compared to 20 adequate controls regarding venous volume, the effect of ouabain on venous volume and signs of left ventricular hypertrophy. Among offspring there were slightly increased amplitudes in the orthogonal ECG as compared to controls but the differences were not statistically significant. Using a plethysmographic technique we found a significantly lower venous volume of the forearm in the offspring than in controls. There was, however, no effect of ouabain on the venous volume. The decreased venous distensibility among normotensive offspring might be an early manifestation of essential hypertension.     

Reactivity of Mesenteric Arteries From Fructose Hypertensive Rats to Endothelin-1

We previously demonstrated that mesenteric arteries from hyperinsulinemic, insulin resistant fructose hypertensive (FH) rats contain a higher absolute amount of ET-1 and exhibit defective endothelium-dependent vasodilation. Furthermore, chronic ET receptor blockade with bosentan completely prevented the rise in blood pressure in these rats. The present study was undertaken to examine 1) whether the reactivity of mesenteric arteries to ET-1 is altered in FH rats, and 2) whether chronic bosentan treatment has any effect on ET-1 responsiveness and endothelium-dependent vasodilation. Male Sprague Dawley rats were divided into four groups: control (C), control bosentan-treated (CB), fructose (F) and fructose bosentan-treated (FB). Chronic oral bosentan treatment (100 mg/kg/day) was initiated in the CB and FB groups 1 week prior to initiating the fructose diet. At week 16, the F group was hyperinsulinemic and hypertensive when compared to the C group (plasma insulin: 5.8 ± 0.3 v C 3.2 ± 0.5 ng/mL, P < .001; systolic BP: 157 ± 5 v C 130 ± 4 mm Hg, P < .001). Treatment of the F group with bosentan prevented the rise in BP (FB: 133 ± 3 mm Hg; P < .001 v F). Analysis of the pressurized mesenteric resistance arterioles demonstrated that the wall thickness as expressed as percentage of internal diameter did not differ between arteries from C and F rats, when measured over a range of transmural pressures. Constrictor responses of resistance arterioles to NE were similar for C and F rats when studied at transmural pressures of either 120 mm Hg or 160 mm Hg, respectively. The maximum contractile response and the sensitivity of superior mesenteric arteries to NE did not differ between the groups, either with or without the endothelium. However, the maximum contractile response to ET-1 was depressed in the F group both with (+) and without (−) the endothelium [(+): 1.50 ± 0.11 v C 1.88 ± 0.1 g/mm³, P < .05, (−): 1.68 ± 0.11 v C 2.05 ± 0.1 g/mm³, P < .05.]. Furthermore, the endothelium intact F arteries exhibited a decreased sensitivity to ET-1 (pD₂ values F 8.36 ± 0.11 v C 8.83 ± 0.07). Chronic bosentan treatment of the F group restored the maximum tension responses of arteries to ET-1 [(+) in the FB group: 1.88 ± 0.12 g/mm³ v C, P > .05, (−): 1.95 ± 0.05 g/mm³ v C, P > .05] but had no effect on the responses of the CB group. In arteries with intact endothelium, bosentan treatment restored the sensitivity of the F arteries to ET-1 (pD₂ values FB 8.82 ± 0.05 v C, P < .05). Endothelium-dependent relaxation responses were diminished in the F group, which were unaffected by bosentan treatment. These data suggest that mesenteric arteries from FH demonstrate a specific alteration towards the reactivity to ET-1, which is restored by long-term bosentan treatment.     

In Vitro Vascular Reactivity to Endothelin: A Comparison Between Young and Old Normotensive and Hypertensive Rats

In this study we have investigated whether the vascular smooth muscle of a large capacitance artery of spontaneously hypertensive rats (SHR) is hyperresponsive to endothelin-1 and whether the arterial responsiveness to endothelin-1 is affected by aging. Isometric contractions of spirally cut aortic strips from SHR of 11, 22, 33 and 44 weeks of age and from age-matched WKY were measured in parallel. The vessels from SHR did not exhibit a greater responsiveness to endothelin-1 than those from WKY. No difference of responsiveness to the peptide was found among the arteries isolated from WKY of different ages. In contrast, a progressive decrease of responsiveness to endothelin-1 with aging was observed in SHR. This finding seems to be specific for endothelin-1, since the responsiveness to norepinephrine was unchanged. The significant decrease of aortic responsiveness in SHR with aging might be due to chronic hypertension and indicate desensitization to endothelin-1. The latter might be related to chronic in vivo hyperproduction of endothelin, either genetically determined or related to the hypertension-induced endothelial damage.     

Different Secretion Patterns of Adrenomedullin,Brain Natriuretic Peptide,and Atrial Natriuretic Peptide During Exercise in Hypertensive and Normotensive Subjects

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n=15) and in normotensive controls (n=10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater     

Metabolic Clearance of Norepinephrine in Normotensive and Borderline Hypertensive Subjects

Metabolic clearance of norepinephine (CmNE) has been calculated in 10 normotensive subjects (NT) and 10 borderline hypertensive subjects (HT) at two different infusion rates of 1-NE. Plasma catecholamines have been determined by radio-enzymatic method from arterial blood samples. In these conditions, CmNE is similar in NT and HT.     

Role of Nitric Oxide and Endothelin-1 in a Portal Hypertensive Rat Model

Background: Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1. Methods: Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats, treated by a sham operation (SO), were also studied. Results: Two-step PVL treatment induced a significant increase in the serum level of NO3- and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect. Conclusions: In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa, and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.     

Aortic Distensibility in Normotensive, Untreated and Treated Hypertensive Patients

Background: Compared with normotensive subjects, untreated hypertensive patients show a decrease of their aortic distensibility. Whether antihypertensive treatment, by reducing blood pressure and changing functional and/or structural abnormalities of the arterial wall, may prevent or reverse the arterial damage due to the accelerated ageing process remains unclear. The objective of the present study was to determine, using a cross-sectional approach, whether aortic distensibility as measured by pulse wave velocity, in treated hypertensive patients whose diastolic blood pressure had been normalised for several months, was significantly improved over that of untreated hypertensive patients.

Methods: Carotid femoral pulse wave velocity was measured in 124 normotensive subjects and 388 hypertensive patients. The latter group included 164 treated patients with well controlled diastolic blood pressure and 224 untreated hypertensive subjects. The three groups did not differ in other cardiovascular risk factors.

Results: In each group there was a significant relationship between age and pulse wave velocity. When compared with untreated hypertensives, treated hypertensives with well controlled diastolic blood pressure had significantly lower blood pressure and pulse wave velocity according to age. However, although diastolic blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, the aortic distensibility of the controlled hypertensives remained reduced showing two characteristics: a faster increase in pulse wave velocity with age and a negative relationship with HDL-cholesterol.

Conclusion: These results suggest that long-term antihypertensive treatment and control of blood pressure using only diastolic blood pressure criteria may not fully reverse arterial alteration associated with hypertensive vascular disease.     

Renin Secretion in Lyon Hypertensive Rats

In genetically hypertensive rats of Lyon strain (LH), both development and maintenance of hypertension are extremely sensitive to the chronic blockade of the renin-angiotensin system. However, LH rats exhibit a low renin secretory profile as indicated by (1) low basal plasma renin concentration; (2) blunted renin responses to reductions of renal perfusion pressure and β-adrenoceptor stimulation both in vitro (isolated perfused kidney) and in vivo (conscious rat). None of the latter abnormalities are corrected by chronic sodium deprivation or when hypertension is prevented by hydralazine or perindopril treatment. Future studies will therefore have to elucidate the ‘renin paradox’ in LH rats.