摘要:

Here we review the "telomere hypothesis of cellular aging." We propose that this hypothesis is relevant to our understanding of the roles of genetics as well as growth and development in the etiology of essential hypertension and its cardiovascular complications. Elements of this hypothesis and the speculations that we make can be directly tested using tissues (cells) obtained from human beings. (Hypertension. 1997;29:1067-1072.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We measured blood pressure and related clinical phenotypes in 497 adult native Canadians from an isolated community in Northern Ontario. We analyzed their DNA for genotypes of angiotensinogen. We found that the frequency of the T235 variant of the angiotensinogen gene was 0.89 in this sample. This variant was associated with a significantly increased systolic pressure but not diastolic pressure. We also found that sex and body mass were each highly significantly associated with variation in both systolic and diastolic pressures. We found a significant association between age and variation in systolic pressure but not diastolic pressure. We also found a highly significant association between plasma apolipoprotein B concentration and variation in diastolic pressure but not systolic pressure. The high frequency of the angiotensinogen T235 variant suggests that subjects in this young, essentially normotensive population might be predisposed to hypertension, which may become more apparent in the presence of secondary factors. (Hypertension. 1997;29:1073-1077.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A variant of the angiotensinogen gene (AGT) that encodes for threonine at codon 235 (T235) has been associated with a higher serum angiotensinogen concentration and with hypertension in white subjects. The frequency of T235 is about two times higher in blacks than whites, suggesting that AGT may contribute to the susceptibility to hypertension in blacks more than it does in whites. However, an association of T235 with angiotensinogen level or blood pressure has not been observed in blacks, possibly because the high prevalence of T235 makes it insufficiently informative as a marker. For this reason, we undertook to further differentiate the T235 carrier state by constructing haplotypes with alleles in the 5' upstream region of AGT. One such haplotype, [en dash]1074t;T235, showed a significant association with angiotensinogen level in a cohort of black and white children and adolescents (76 blacks, mean age = 12.3 +/- 2.0 [SD] years; 139 whites, mean age = 12.4 + 1.8 years). With a linear regression model, the level of serum angiotensinogen was significantly related to body mass index (P = .0017) and the haplotype (P = .0001). Within specific race groups, the haplotype was significantly related to serum angiotensinogen in both the blacks (P = .0277) and whites (P = .0001). The mean level of angiotensinogen was higher in the blacks carrying a single copy of the haplotype than in those without the haplotype (1472.2 +/- 68.4 versus 1274.9 +/- 46.7 nmol angiotensin I/L), a difference that was marginally significant (P = .0609). In the whites, the level of angiotensinogen was also higher in carriers of a single copy than in those with no copy (1527.9 +/- 71.2 versus 1099.2 +/- 20.1 nmol angiotensin I/L) (P = .0003). Serum angiotensinogen level did not increase with two copies of the haplotype, but in each racial group, there were only four individuals who were homozygous. The haplotype showed a marginally significant relation (P = .0757) to the mean of longitudinally determined diastolic pressures adjusted for body mass index, race, sex, and age. In summary, using a haplotype to differentiate further the T235 carrier state, we observed an association of genotype with serum angiotensinogen level and blood pressure in blacks and whites. The findings suggest that AGT may play an important role in blood pressure regulation in both racial groups. (Hypertension. 1997;29:1078-1082.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Acute vasopressor responses to stress are adrenergically mediated and hence potentially subject to differential modulation by dietary potassium and sodium. The greater vasopressor responsiveness in blacks compared with whites might then be consequent not only to a high dietary salt intake but also to a marginally reduced dietary potassium intake. Under controlled metabolic conditions, we compared acute vasopressor responses to cold and mental stress in black and white normotensive men during three successive dietary periods: (1) while dietary potassium was reduced (30 mmol K+/70kg per day) and salt was restricted (10 to 14 days); (2) while salt was loaded (15 to 250 mmol Na+/70kg per day) (7 days); and (3) while salt loading was continued and potassium was either supplemented (70 mmol K+/70kg per day) (7 to 21 days) in 9 blacks and 6 whites or continued reduced (30 mmol K+/70kg per day) (28 days) in 4 blacks (time controls). At the lower potassium intake, cold-induced increase in forearm vascular resistance in blacks was twice that in whites during both salt restriction and salt loading. Normalization of dietary potassium attenuated cold-induced increases in both forearm vascular resistance and systolic and diastolic blood pressures in blacks but only in systolic pressure in whites. In blacks but not in whites, normalization of dietary potassium attenuated mental stress-induced increases in systolic and diastolic pressures. In normotensive blacks but not whites, a marginally reduced dietary intake of potassium reversibly enhances adrenergically mediated vasopressor responsiveness to stress. That responsiveness so enhanced over time might contribute to the pathogenesis of hypertension in blacks. (Hypertension. 1997;29:1083-1090.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Ca2+channel blockers may cause cancer by inhibiting apoptosis or reducing intracellular Ca2+in certain tissues. Recent findings suggest that drug users are at increased risk for cancer in general and for colon cancer in particular. We conducted a study in one Danish county of 17 911 patients who received at least one prescription of Ca2+channel blockers between 1 January 1991 and 31 December 1993. The patients were identified from records in the National Health Insurance Program, which refunds part of the price of such drugs. Cancer occurrence and rate were determined by use of the files of the Danish Cancer Registry and compared with county-specific incidence rates for various categories of cancer. During the follow-up period of up to 3 years, 412 cancers were observed among users of Ca2+channel blockers, compared with 414 expected, to yield an age- and sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to 1.10). There was no indication of an excess risk in the subgroup of likely long-term users or users of specific drugs. The SIR of colon cancer, a site of a priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34 cases. Although the results are reassuring, the lack of association could reflect the relatively short follow-up after registration in the prescription database. Continued monitoring of cancer risk is planned. (Hypertension. 1997;29:1091-1094.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2= .13) and LV posterior wall thickness (R2= .14) than for LV mass (R2= .37) and LV diastolic dimension (R (2) = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly. (Hypertension. 1997;29:1095-1103.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The purpose of the present study was to test the hypothesis that hypertension induced by reduced renal mass (RRM) upregulates gene expression of the type 1 angiotensin II (Ang II) receptor (AT1) in the thoracic aorta and heart through an Ang II-dependent mechanism. Three groups of rats were given 1% NaCl water and subjected to RRM, RRM plus captopril (RRM + Cap, 30 mg/kg per day), or sham surgery. Tail-cuff systolic blood pressure was significantly elevated in RRM and RRM + Cap rats compared with sham-operated rats. The ratios of the medial wall area of the thoracic aorta and heart weight to body weight were significantly elevated in RRM and RRM + Cap rats compared with sham-operated rats. Northern blot analysis indicated that the ratio of AT1to GAPDH mRNA in the aorta was significantly higher in RRM (1.85 +/- 0.52) compared with sham-operated (0.21 +/- 0.04) and RRM + Cap (0.55 +/- 0.20) rats. In contrast, the ratio of AT (1) to GAPDH mRNA in the heart was significantly increased in both RRM (1.09 +/- 0.23) and RRM + Cap (1.00 +/- 0.09) compared with sham-operated (0.34 +/- 0.06) rats. Thus, RRM hypertension upregulates AT1mRNA expression in both the hypertrophied aorta and heart. Captopril treatment without altering blood pressure in RRM rats prevents the increase in AT1mRNA in the aorta but not the heart. These results suggest that different tissue-specific mechanisms of AT1gene regulation exist; ie, in aorta, an Ang II- or kinin-dependent mechanism is operant, whereas in heart, RRM-induced upregulation of AT (1) mRNA may be pressure dependent. (Hypertension. 1997;29:1104-1108.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

140/90 mm Hg). The 95% confidence interval for each subject's blood pressure was also determined. For example, if 40 ambulatory blood pressure measurements are performed on a subject and the average systolic ambulatory blood pressure is 137 mm Hg, then there is a 10% probability that the patient's "true" average blood pressure is actually in the hypertensive range. By contrast, if the systolic pressure is 143 mm Hg, there is a 90% probability that the patient is hypertensive. This approach may be useful for clinical decision making and also for the design of clinical trials. (Hypertension. 1997;29:1109-1113.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The contribution of carbon monoxide (CO) to the acute cardiovascular effects of smoking is not clear. Using a double-blind, randomized, vehicle-controlled study design, we examined the sympathetic and vascular responses to modest increases in carboxyhemoglobin in 10 healthy humans. We measured muscle sympathetic nerve activity (microneurography), forearm blood flow (plethysmography), heart rate, blood pressure, and minute ventilation at baseline and during 60 minutes of CO inhalation (1000 ppm during the first 30 minutes and 100 ppm during the last 30 minutes). The same measurements were made in a vehicle session (room air inhalation) on a separate day. During the first 30 minutes of CO inhalation, carboxyhemoglobin levels increased progressively from 0.2 +/- 0.1% to 8.3 +/- 0.5% and were maintained at about this level for a further 30 minutes. Forearm vascular resistance did not change with CO but increased slightly with vehicle; the effects of CO on muscle sympathetic nerve activity, forearm blood flow, blood pressure, heart rate, and minute ventilation were not significantly different from the effects of vehicle. Modest increases in carboxyhemoglobin levels equivalent to those resulting from cigarette smoking are unlikely to contribute to the acute sympathetic and hemodynamic effects of smoking in healthy humans. (Hypertension. 1997;29:1114-1118.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We used complex demodulation of cardiac interval and systolic arterial blood pressure oscillations in the low-frequency band (0.04 to 0.14 Hz) to investigate baroreceptor control of heart rate. Baroreflex sensitivity was defined as the instantaneous amplitude of complex-demodulated oscillations in the RR interval divided by the instantaneous amplitude of complex-demodulated oscillations in systolic blood pressure. We evaluated the method using both simulated and actual data obtained from 33 healthy nonsmokers during supine and standing postures. To test the validity and reliability of the method, we compared the mean values of baroreflex sensitivity calculated using complex demodulation with the values obtained using power spectral analysis and sequential analysis of spontaneous variations in blood pressure and RR interval. All three methods applied to the simulated data yielded the same values of baroreceptor sensitivity. Mean values of baroreflex sensitivity assessed by complex demodulation of the actual data were similar to those calculated by both power spectral analysis and sequential analysis (13.9 +/- 5.2 versus 13.7 +/- 6.7 or 14.3 +/- 6.5 ms/mm Hg for supine and 7.3 +/- 2.8 versus 7.0 +/- 3.0 or 7.2 +/- 2.8 ms/mm Hg for standing, respectively). In addition, a significant correlation existed between the values obtained by complex demodulation and power spectral analysis (r = .97, P = .0001) and sequential analysis (r = .98, P = .0001). Furthermore, complex demodulation-derived baroreflex sensitivity fluctuated across time during both the supine and standing postures, and this could not be discerned by power spectral analysis. The results indicate that complex demodulation provides a dynamic assessment of baroreflex sensitivity and may be a useful tool in exploring reflex autonomic control of the cardiovascular system. (Hypertension. 1997;29:1119-1125.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID