摘要:

The genetic basis of hypertension in the genetically/hereditary hypertensive (BPH/2) mouse strain is incompletely understood, although a recent genome scan uncovered evidence for several susceptibility loci. To probe the neuroendocrine transcriptome in this disease model, 12 488 probe set microarray experiments were performed on mRNA transcripts from adrenal glands of juvenile (prehypertensive) and adult BPH/2 (hypertensive), as well as the genetically/hereditary low-blood pressure (BPL/1), strains at both time points. To determine the impact of strain (BPH/2 versus BPL/1), age (juvenile versus adult), and the interaction of strain and age on gene expression levels, we performed standard 2-factor ANOVA and computed a concordance coefficient to assess the reproducibility of gene expression measurements among replicates. Of genes with significant (P<0.05) differential expression, 2647 showed strain differences, 982 showed age differences, and 757 exhibited strain-by-age interaction. Fold-changes in gene expression assayed by microarray were confirmed in a subset by real-time polymerase chain reaction (R=0.739,P=0.0094). We used a systems biology approach to evaluate alterations in contributing biochemical pathways and we statistically quantified these global pathway disturbances using the Kolmogorov-Smirnov goodness-of-fit test. We found widespread, indeed global, alterations in patterns of gene expression in diverse systems of BPH/2: in sympathochromaffin transcripts suggesting increased sympathetic stimulation; in vasoconstrictor/vasodilator systems; global reductions in carbohydrate intermediary metabolism; and increases in oxidative stress, with changes in oxygen radical forming and disposition enzymes. These analyses highlight widespread derangements in diverse physiological pathways, providing multiple avenues for further investigation into the pathogenesis of genetic hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

The present study examined whether blockade of melanocortin receptors subtypes 3 and 4 (MC3/4-R) inhibits chronic cardiovascular and dietary responses to leptin infusion. A cannula was placed in the lateral ventricle of male Sprague-Dawley rats for chronic intracerebroventricular (ICV) infusion via osmotic minipump, and arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and IV infusions. After a 5-day control period, rats received (1) 0.9% saline vehicle ICV for 12 days plus leptin (1 μg/kg per minute IV, n=5) during the final 7 days; (2) MC3/4-R antagonist SHU-9119 (1 nmol/h ICV) for 12 days plus leptin (1 μg/kg per minute IV, n=6) during the final 7 days; and (3) SHU-9119 (1 nmol/h ICV, n=8) for 12 days. Leptin infusion in vehicle-treated rats caused a small increase in MAP (5±1 mm Hg) despite reduced food intake (23±1 to 10±1 g/d) and decreased body weight (−6%±1%). SHU-9119 infusion completely prevented the cardiovascular and dietary actions of leptin, leading to increased food intake (23±1 to 49±4 g/d) and body weight (+30%±2%), markedly decreased HR (−77±9 bpm), and caused a decrease in MAP (−6±1 mm Hg). Similar results were observed when SHU-9119 was infused alone in vehicle-treated rats. Leptin decreased plasma insulin to 30% of control values, an effect that was also abolished by SHU-9119 treatment, which caused a 5-fold increase in plasma insulin concentration. Thus, MC3/4-R antagonism completely blocked the chronic cardiovascular, satiety, and metabolic effects of leptin, suggesting that the hypothalamic melanocortin system plays an important role in mediating these actions of leptin.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Adiponectin is one of the key molecules in the metabolic syndrome, and its concentration is decreased in obesity, type-2 diabetes, and coronary artery disease. Genetic investigation has revealed that 2 polymorphisms (I164T and G276T) are related to adiponectin concentration and diabetes. To examine whether adiponectin affects hypertension genetically or biologically, we performed a case-control study. A total of 446 diagnosed cases of hypertension (HT) in men and 312 normotensive (NT) men were enrolled in this study. Plasma adiponectin concentration was measured using an enzyme-linked immunosorbent assay system. Single nucleotide polymorphisms were determined by TaqMan polymerase chain reaction method. After adjustment for confounding factors, adiponectin concentration was significantly lower in HT (HT: 5.2±0.2 μg/mL; NT: 6.1±0.2 μg/mL;P<0.001). Furthermore, multiple regression analysis indicated that hypoadiponectinemia was an independent risk factor for hypertension (P<0.001). Blood pressure was inversely associated with adiponectin concentration in normotensives regardless of insulin resistance. In subjects carrying the TC genotype of the I164T polymorphism, adiponectin concentration was significantly lower (TC: 2.6±0.9 μg/mL; TT: 5.5±0.1 μg/mL;P<0.01), and most of them had hypertension. In contrast, the G276T polymorphism was not associated with adiponectin concentration or hypertension. In conclusion, hypoadiponectinemia is a marker for predisposition to hypertension in men.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

The association between insulin resistance and insulinemia and hypertension is controversial. We examined the relation between insulin resistance and hypertension in 564 non-Hispanic whites (NHW), 505 Hispanics (H), and 413 African Americans (AA) who participated in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity was measured with a frequently sampled intravenous glucose tolerance test with minimal model analysis. The prevalence of hypertension was 32.5%, 49.4%, and 32.3% in NHW, AA, and H, respectively (P< 0.001). When subjects without diabetes in all ethnic groups were combined, age, male sex, race (AA), body mass index (BMI), and insulin resistance, but not fasting insulin, were significantly associated with hypertension. When each ethnic group was analyzed separately, insulin resistance was significantly associated with hypertension in NHW and H, but not AA. After excluding subjects taking antihypertensive medications, male sex, BMI, fasting glucose, and insulin resistance, but not fasting insulin, were significant determinants of blood pressure. When the 3 ethnic groups were analyzed separately, insulin resistance was significantly associated with blood pressure in H, but not NHW, or AA. Neither insulin resistance nor fasting insulin was significantly associated with hypertension or blood pressure in subjects with diabetes of the 3 ethnic groups after adjusting for age, sex, BMI, and waist. In conclusion, insulin resistance, but not insulinemia, was related to hypertension and blood pressure in subjects without diabetes, but ethnic differences in these relations appear to exist. Neither insulin resistance nor insulinemia was related to hypertension or blood pressure in patients with type 2 diabetes in the 3 ethnic groups.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Blood pressure and prevalence of high blood pressure are greater for northern than southern Chinese. Reasons for these differences are unclear. Relationships of north–south blood pressure differences with multiple dietary factors were investigated in 839 Chinese participants, International Study on Macronutrients and Blood Pressure (INTERMAP), 561 northern, 278 southern, aged 40 to 59 years. Daily nutrient intakes were determined from four 24-hour dietary recalls and 2 timed 24-hour urine collections. Average systolic/diastolic pressure levels were 7.4/6.9 mm Hg higher for northern than southern participants. Southern participants had lower body mass index, sodium intake, sodium/potassium ratio, and higher intake of calcium, magnesium, phosphorus, and vitamins A and C. Considered singly, with control for age and gender, several dietary variables (eg, body mass index, urinary sodium/potassium ratio, urinary sodium, dietary phosphorus, and magnesium) reduced north–south blood pressure differences by ≥10%. Controlled for age and gender, nondietary variables had little effect on north–south blood pressure differences. With inclusion in regression models of multiple dietary variables (sodium, potassium, magnesium or phosphorus, body mass index), north–south blood pressure differences became much smaller (systolic −1.1, diastolic 1.6 mm Hg) and statistically nonsignificant. In conclusion, multiple dietary factors accounted importantly for north–south blood pressure differences. Efforts are needed to improve nutrition in China, especially in the north, as well as in other populations including those in the United States, for prevention and control of adverse blood pressure levels and major adult cardiovascular disease.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Goal blood pressure (BP) was defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) and the World Health Organization–International Society of Hypertension (WHO/ISH) as <140 mm Hg systolic and <90 mm Hg diastolic for the general and <130 mm Hg systolic and <85 mm Hg diastolic for special high-risk populations. However, there are few reports that address BP control among special subgroups of hypertensives by reference to targeted BP. We therefore conducted a study to evaluate BP control of 4049 hypertensives in 47 hospital-based hypertension units in Spain. Overall, 42% of patients achieved goal BP (<140 mm Hg systolic and <90 mm Hg diastolic). Only 13% of diabetic patients and 17% of those with renal disease achieved the BP goal (<130 mm Hg systolic and <85 mm Hg diastolic), and only 10% and 12%, respectively, achieved the even more rigorous goal (<130 mm Hg systolic and <80 mm Hg diastolic). Likewise, only 18% of patients in JNC-VI risk group C and 17% of WHO/ISH high-risk patients attained a goal BP <130 mm Hg systolic and <85 mm Hg diastolic. BP control (<125 mm Hg systolic and <75 mm Hg diastolic) was extremely low (2%) in patients with proteinuria >1 g/d. Poorer BP control was observed among patients at high risk, with diabetes, renal disease, or obesity, than in lower-risk groups. BP control was lower for systolic than for diastolic BP. In >50% of uncontrolled patients, no measures were taken by doctors to optimize pharmacologic treatment, and approximately one-third of patients were still using drug monotherapy. Control of BP, particularly of systolic BP, is still far from optimal in hospital-based hypertension units. Patients at high risk, with diabetes or proteinuria, warrant focused attention. Moreover, a more aggressive behavior of doctors treating uncontrolled hypertension is needed.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID