ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The SA gene is expressed at 10-fold greater levels in the kidney of the spontaneously hypertensive rat compared with the normotensive Wistar-Kyoto rat. The gene is linked to blood pressure levels in a number of crosses involving the spontaneously hypertensive rat and other strains of genetically hypertensive rats. To assess its role in human hypertension, a human SA cDNA was cloned from a liver library. The cDNA was 1513 bp in length and exhibited a high identity with the published rat SA cDNA sequence in the coding region. A microsatellite marker was developed from a yeast artificial chromosome clone containing SA and mapped by linkage to human chromosome 16p13.11-12.3. Polymerase chain reaction amplification of human genomic DNA revealed two introns located in the SA gene, one of which contains a frequent polymorphism due to a single nucleotide substitution (cytosine to thymidine at residue 79 of the intron). Association and linkage studies in a large sample of hypertensive patients, normotensive control subjects, and multiplex sibships with these markers and other microsatellites in close proximity to SA revealed no evidence favoring involvement of the gene in the disease in humans. The methodology used in this study can be applied to the evaluation of other novel candidate genes obtained from investigations of experimental models of hereditary hypertension. (Hypertension. 1995;25:6-13.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT (1) receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1receptor blockade, did not fall. Compared with baseline values, plasma norepinephrine increased moderately with the 100-mg but not with 25- or 1-mg dose. Serum uric acid and its 24-hour urinary excretion did not change. In conclusion, in essential hypertension, once-daily irbesartan effectively lowers blood pressure. This effect is maintained for 24 hours with a 100-mg dose. Unlike the AT1receptor antagonist losartan, irbesartan exerts no uricosuric effect, suggesting that this is an effect unrelated to AT1receptor blockade. (Hypertension. 1995;25:22-29.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To investigate the pathogenesis of hypertension in patients with obesity and insulin resistance and to explore the role of plasma lipids, we studied 30 subjects at the end of 7 days of low (20 mEq/d) then high (200 mEq/d) sodium diets. Glucose and insulin tolerance tests were performed at the end of each week and blood and urine collected for measurements of plasma aldosterone, renin activity, electrolytes, insulin, and lipoproteins. There was a strong negative correlation between plasma aldosterone and high-density lipoprotein cholesterol during both diets. There were weaker positive correlations between plasma aldosterone and insulin or triglycerides. When the aldosterone-renin ratio was the dependent variable and the correlation controlled for serum potassium, the inverse relationship with high-density lipoprotein cholesterol and the positive correlation with insulin remained, but only during the high salt diet. Subjects were divided into three groups based on high-density lipoprotein cholesterol. Subjects with the lowest high-density lipoprotein cholesterol levels showed the highest aldosterone, plasma triglycerides, body mass index, and waist-to-hip ratio. Those subjects also demonstrated the greatest resistance to insulin action on glucose and plasma unesterified fatty acids. There was a weak direct correlation between plasma aldosterone and systolic blood pressure during the high salt diet. These data suggest that high aldosterone levels may be a link between dyslipidemia, insulin resistance, and hypertension, a relationship made more evident by high salt intake. (Hypertension. 1995;25:30-36.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n = 51) were allocated to placebo, 25 or 100 mg losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrations, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 and 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hours after dosing, compared with the run-in day, 100 mg losartan increased plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapril increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, plasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of losartan, plasma renin activity and Ang II changes were similar to placebo changes by 36 hours. These results indicate that long-term blockade of the feedback Ang II receptor in hypertensive patients produces modest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist. (Hypertension. 1995;25:37-46.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To investigate the influence of antihypertensive therapy and the success of blood pressure control on coronary heart disease incidence and total mortality, we studied dyslipidemic middle-aged men participating in the placebo arm of the Helsinki Heart Study, a randomized coronary primary prevention trial with gemfibrozil. Based on blood pressure level and the presence of antihypertensive therapy at study entry, the participants were classified into four categories. Relative risks of coronary heart disease (nonfatal myocardial infarction or cardiac death) and total mortality during the 5-year trial period were calculated using Cox proportional hazards models. With subjects who were not using antihypertensive drugs and who had normal blood pressure (category I) as reference, the relative risks of coronary heart disease during the trial period were 2.1 (95% confidence interval [CI], 1.3 to 3.3) in untreated hypertensive subjects (category II), 0.9 (95% CI, 0.2 to 3.8) in subjects with successful antihypertensive therapy (category III),and 2.0 (95% CI, 1.0 to 4.1) in subjects who remained hypertensive despite drug therapy (category IV). The relative risks of death were 1.9 (95% CI, 0.9 to 3.9) in category II and 1.0 (95% CI, 0.1 to 7.3) in category III; in category IV subjects, those with unsuccessful antihypertensive therapy, the relative risk was 4.4 (95% CI, 2.0 to 9.6). The excess mortality in this category was due to cardiovascular causes and was clustered in subjects with multiple drug therapy for hypertension control. We conclude that successful antihypertensive therapy in dyslipidemic men reduced coronary heart disease incidence despite its adverse effects on high-density lipoprotein cholesterol and triglycerides. With regard to total mortality, adequate blood pressure reduction had a positive effect, and unsuccessful hypertension control increased total mortality, especially cardiovascular mortality. (Hypertension. 1995;25:47-52.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To examine the association between long-term exposure to inorganic arsenic and the prevalence of hypertension, we studied a total of 382 men and 516 women residing in villages where arseniasis was hyperendemic. Hypertension was defined as a systolic blood pressure of 160 mm Hg or greater, a diastolic blood pressure of 95 mm Hg or greater, or a history of hypertension treated regularly with antihypertensive drugs. The long-term arsenic exposure was calculated from the history of artesian well water consumption obtained through standardized interviews based on a structured questionnaire and the measured arsenic concentration in well water. Residents in villages where long-term arseniasis was hyperendemic had a 1.5-fold increase in age- and sex-adjusted prevalence of hypertension compared with residents in nonendemic areas. Duration of artesian well water consumption, average arsenic concentration in drinking water, and cumulative arsenic exposure were all significantly associated with hypertension prevalence. The higher the cumulative arsenic exposure, the higher the prevalence of hypertension. This dose-response relation remained significant after adjustment for age, sex, diabetes mellitus, proteinuria, body mass index, and serum triglyceride level. The results suggest that long-term arsenic exposure may induce hypertension in humans. (Hypertension. 1995;25:53-60.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

L-Arginine is the physiological substrate of nitric oxide, a vasodilator that controls blood pressure and renal hemodynamics in the basal state. In the present studies, we produced chronic nitric oxide blockade by oral administration of the L-arginine analogue NG-nitro-L-arginine methyl ester, which produced sustained hypertension and increased renal vascular resistance in conscious rats. Acute excess L-arginine had little effect on blood pressure but completely normalized renal vascular resistance and increased renal plasma flow in chronically nitric oxide-blocked hypertensive rats. In contrast to L-arginine, D-arginine had no renal hemodynamic effects in either normal or chronically nitric oxide-blocked rats. Acutely administered glycine was ineffective in vasodilating the chronically nitric oxide-blocked rat kidney, in a dose that produced renal vasodilation in normal rats. These findings indicate the following: (1) Hypertension induced by chronic nitric oxide blockade due to substituted L-arginine analogue cannot be acutely reversed with excess L-arginine, suggesting that the maintenance of the hypertension is not solely caused by competitive inhibition of nitric oxide production; (2) in contrast, the kidney remains responsive to L-arginine whereas the renal vasodilator response to glycine is abolished in this model of hypertension. (Hypertension. 1995;25:61-66.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID