ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The Captopril Prevention Project (CAPPP) is a prospective, randomized, multi-centre intervention trial designed to investigate whether antihypertensive treatment with the angiotensin converting enzyme (ACE) inhibitor captopril may reduce cardiovascular mortality and morbidity more than a therapeutic regimen which does not include an ACE inhibitor. Secondary objectives are to compare total mortality, the development or deterioration of ischaemic heart disease, left ventricular failure, atrial fibrillation, diabetes mellitus and possible differences in renal function in the two groups. Male and female patients with essential hypertension, aged 25—66 years, will be randomly allocated to antihypertensive treatment which will comprise either the use of the ACE inhibitor captopril or will exclude all types of ACE inhibitors. Some 275 hypertension centres and health care centres in Sweden and Finland will take part in this multi-centre trial. A total of 7000 patients will be recruited and studied for an average period of 5 years, the assumption being that a 20% difference in cardiovascular mortality between the two groups can be detected with a power of 80% at the 5% significance level (two–sided test).

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased ( — 11%,P<0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance ( — 35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P<0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The age-related response to placebo and active antihypertensive treatment was evaluated in 742 elderly hypertensive patients who were followed in the double-blind placebo-controlled trial conducted by the European Working Party on High blood pressure in the Elderly (EWPHE). In the two treatment groups, the fall in systolic and diastolic blood pressures after 3 months was negatively correlated with age (P<0.02), indicating that the hypotensive effect of placebo and active treatment was more pronounced in older patients. Further comparison of the two treatment groups failed to demonstrate any statistical differences in the slopes of the hypotensive effect on age. These conclusions were not altered by cumulative adjustments for baseline blood pressure, pulse rate, serum creatinine and the presence of cardiovascular complications at entry. In conclusion, in the present study, a similar blood-pressure-lowering action which increased with age was observed on active and placebo treatment; thus, proof that an observed age-related hypotensive effect is caused by a particular drug requires comparison with a control group on placebo.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have investigated the growth characteristics of adult rat ventricular cells (ARVC) in culture from 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar—Kyoto rats (WKY). Protein synthesis in ARVC estimated from tritiated leucine uptake was augmented in both strains after exposure of cells to either norepinephrine or fetal bovine serum (FBS), but the response was significantly smaller in SHR than in WKY. A relative increase in the protein content of ARVC incubated with norepinephrine or FBS was also smaller in SHR than in WKY. These results demonstrate that SHR cardiac myocytes are not genetically growth-accelerated and show a decreased growth response to growth stimuli such as norepinephrine and serum during the adult period.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Hypertension and nephrotoxicity are major clinical problems associated with cyclosporine A administration. Sheep rapidly develop hypertension after intravenous administration of cyclosporine A at 6 mg/kg per day over 5 days, and this is associated with a rise in peripheral resistance. Nephrotoxicity is not a feature of cyclosporine A-induced hypertension in this species. This study reports the use of nisoldipine to investigate the role of Ca2+-induced smooth muscle contraction in cyclosporine A-induced hypertension in conscious sheep. After 3 control days, nisoldipine at 24mg/day was infused intravenously alone for 24 h (E1), followed by 5 days of nisoldipine plus cyclosporine A (6 mg/kg per day; E2–E6). After 24 h of nisoldipine alone, mean arterial pressure (MAP) was unchanged, heart rate rose from a control value of 60 ± 2 beats/min to 102 ± 9 beats/min (P≤ 0.001), calculated total perip/eral resistance (CTPR) fell from 15.8 ± 0.5 to 11.7 ± 0.5 mmHg/l per min (P≤ 0.001) and stroke volume fell from 73 ± 4 ml/beat to 60 ± 5 ml/beat (P/ 0.01). With nisoldipine plus cyclosporine A (E2–E6), MAP rose from 67 ± 1 mmHg to 82 ± 2 mmHg on E6 (P≤ 0.001), heart rate remained high to peak at 136 ± 11 beat/min (P≤ 0.001) on E6, CTPR was only significantly higher on E5, when it was 19 ± 1 mmHg/l per min (P≤ 0.05) and stroke volume fell to 34 ± 4ml/beat (P<0.001). Both plasma Na+and K+concentration fell significantly throughout the nisoldipine plus cyclosporine A, as did urinary K+excretion. Urinary volume and Na+excretion increased during the combined infusion. Renal plasma flow, measured on E6, was not different from control, but glomerular filtration rate increased and filtration fraction rose. The nisoldipine alone for 6 days did not produce sustained haemodynamic effects. Thus, nisoldipine did not prevent the rise in blood pressure produced by cyclosporine A in conscious sheep. The mechanisms by which cyclosporine A increases peripheral resistance and blood pressure in the absence of reductions in renal function remain to be defined.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance=3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184 s) compared with either diltiazem (0.175 s) or atenolol (0.174 s) alone, or placebo (0.164 s); s.e.m. by analysis of variance=0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Male Sprague—Dawley rats were uninephrectomized and given either deoxycorticosterone (DOC) pivalate (12.5 mg three times weekly) and 1% NaCI/0.2% KCI to drink for 4 weeks (DOC-treated), after which DOC was stopped and tap water substituted (post-DOC), or tap water to drink throughout (controls). DOC treatment increased blood pressure, serum sodium, plasma atrial natriuretic peptide (P-ANP) and plasma deoxycorticosterone (P-DOC) (P<0.05), while serum potassium, plasma renin and plasma angiotensin II were lower (P<0.05) than in control animals. Plasma vasopressin (P-AVP) was also raised but not significantly. These changes persisted for up to 4 weeks post-DOC and, in the case of plasma renin, plasma angiotensin II, P-AVP and P-ANP, for up to 12 weeks. Total body sodium was also increased at 2 weeks post-DOC (P<0.05). Rats which were adrenalectomized after 4 weeks of DOC treatment in which DOC injections were stopped, then drank either NaCI/KCI or tap water; blood pressure and P-DOC remained elevated while plasma renin remained suppressed. There were more deaths in rats given NaCI/KCI (five of six) than in the group given water (one of six). Rats treated with a subcutaneous DOC silastic implant had a comparable rise in blood pressure to rats given DOC injections. However, after removal of the implant, while blood pressure remained elevated, P-DOC levels were not raised and plasma renin rose to control levels after 4 weeks. These findings indicate that, in rats given DOC injections, post-DOC hypertension results from sodium and fluid retention as a consequence of chronic hangover of exogenously administered DOC.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have assessed the in vivo activity of the Na+–H+antiporter skeletal muscle in spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) controls using phosphorus (31P) nuclear magnetic resonance spectroscopy to measure changes in cytosolic acid concentrations during isometric contraction. During contraction there was a smaller rate of rise in skeletal muscle cytosolic acid concentration to a smaller maximum concentration in SHR. This difference in acid response was removed by amiloride and was not attributable to differences in cell buffering or the rate of production of lactic acid, suggesting that the difference in acid response in SHR skeletal muscle is due to increased in vivo Na+–H+antiporter activity. Amiloride reduced resting muscle glycogen concentration and increased muscle lactate concentration in the SHR. This could be related to altered in vivo calcium metabolism. The maximum tension produced by skeletal muscle during contraction in SHR was less than in WKY rats, and relaxation between twitches was significantly greater, consistent with the finding of increased vascular smooth muscle relaxation in essential hypertension. Since increased Na+–H+antiporter activity occurs in association with increased relaxation of both skeletal and vascular smooth muscle, these data are not consistent with a relationship between increased Na+– H+antiporter activity and increased maximal muscle tension development. However, they show that increased Na+–H+antiporter activity is associated with increased muscle relaxation.

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID