ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The sensitivity of tissue to insulin is of physiological, pathophysiological and therapeutic relevance. The quantity of insulin and the response to insulin are paramount complementary factors in the regulation of glucose metabolism, and may, at least under certain pathophysiological conditions, also affect cardiovascular function. Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinaemia due to obesity, impaired glucose tolerance, non-insulin-dependent diabetes mellitus, and certain other conditions. There is evidence that, even in the absence of obesity or diabetes mellitus, essential hypertension tends to be associated with insulin resistance. The latter elicits a compensatory increase in insulin secretion. Hyperinsulinaemia also occurs in diabetes type 1 as a consequence of insulin treatment. Considering the acute effects of insulin on sympathetic nervous activity, transmembranous cation transport, renal sodium reabsorption, cellular proliferation and lipid metabolism, insulin resistance and/or hyperinsulinaemia may possibly contribute to the genesis of essential, obesity-associated and diabetes-associated hypertension, and may also promote dyslipidaemia in these disorders

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

It has been suggested that there is a negative-feedback interaction between the humoral renomedullary antihypertensive system and angiotensin II. If so, the acute blood pressure-lowering effects of angiotensin converting enzyme (ACE) inhibitors might be due, in part, to an increased secretion of renomedullary depressor substances. Groups of anaesthetized Wistar-Kyoto rats (WKY) with an intact or chemically destroyed renal medulla received either saline or the ACE inhibitor enalapril, and mean arterial pressure (MAP), heart rate and renal function were measured. MAP was clearly decreased after enalapril administration in the WKY controls with an intact renal medulla, but was not changed in the medullectomized group. In one WKY control group, where the prostaglandin and kallikrein-kinin systems had also been acutely blocked, the MAP reduction after enalapril was even more marked than in the intact controls. Thus, the acute blood pressure-lowering effect of enalapril is clearly dependent on an intact renal medulla, further suggesting that the renomedullary antihypertensive system is important to normal blood pressure homeostasis

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In order to determine the effect of dietary calcium supplementation on blood pressure and calciotropic hormones, we studied two groups (n = 12 each) of mineralocorticoid [deoxycorticosterone (DOC)]-salt hypertensive rats, one receiving a normal-calcium diet (0.6% calcium, as calcium carbonate) and the other a high-calcium diet (2.5% calcium), over an 8-week period. Dietary calcium supplementation significantly attenuated the rise in blood pressure. Serum ionized calcium concentrations were significantly decreased from baseline levels in both groups but tended to be higher among the calcium-supplemented rats. Serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3(1,25-D) were significantly higher in the DOC-salt rats than in normotensive rats fed normal rat chow [PTH: 49±4 versus 15±0.9pg/ml (means ± s.e.m.); 1,25-D: 108 ± 7 versus 73±13pg/ml, in DOC-salt and normotensive rats, respectively]. In the DOC-salt rats, dietary calcium supplementation did not significantly lower the elevated serum concentration of PTH (from 49±4 to 40 ±4pg/ml; NS), but did significantly reduce that of 1,25-D (from 108±7 to 66±8pg/ml;P< 0.01). Since 1,25-D may increase vascular smooth muscle calcium uptake, dietary calcium supplementation may lower blood pressure in DOC-salt hypertension, in part, by suppressing 1,25-D

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In 1986, the Committee on Safety of Medicines published a report suggesting that enalapril may have an adverse effect on renal function. The prescription event monitoring scheme subsequently published figures on adverse drug reactions and mortality for patients treated with enalapril. They concluded that enalapril did not have an adverse effect on renal function and survival. Similar data were not available for captopril, as the drug was marketed before prescription event monitoring had been developed. In the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP), 368 hypertensive patients treated with captopril and 371 treated with enalapril were followed for an average of 3.1 and 1.6 years, respectively. Thirty-two patients died; none had renal failure as an underlying cause of death. The death rate was similar in both drug groups, at 17.5 (enalapril) and 24.0 (captopril) per 1000 patient-years. The present report shows that, for patients treated for high blood pressure, the relative risk of mortality with captopril compared with enalapril was 1.37, an insignificant difference (95% confidence interval 0.63, 2.98)

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We analyzed the clinical course of 120 patients who were diagnosed as having primary hypertension and subsequently given standard stepped-care therapy (diuretic, ß-blocker and vasodilator) for 9 years. At the end of the follow-up period, 21 patients (17.5%) had developed overt proteinuria. The initial study showed no difference in systolic blood pressure, age, sex, serum creatinine and its clearance, glucose, cholesterol and triglycerides between these patients and those who had not become proteinuric, but uric acid levels and diastolic blood pressure were higher (bothP< 0.01). An adequate control of blood pressure was obtained and maintained in all patients, who had similar therapeutic needs. During the follow-up period, uric acid levels remained significantly elevated (P< 0.01) in the proteinuric patients, while changes in serum glucose, cholesterol and triglycerides were similar in all patients. These results indicate that long-term treatment of primary hypertensives does not fully protect kidney function and that initially elevated uric acid levels could be a predictor of a poor prognosis

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Many membrane abnormalities have been described in human essential hypertension that may lead to an increased intracellular Na+content, an example being reduced Na+efflux by the sodium pump. We have previously found increased Na+—H+antiport activity in leucocytes of hypertensive subjects. In the present study we examined the kinetics of this pump in 16 hypertensive and 20 carefully matched normotensive subjects by loading cells to different intracellular pH levels (as measured by fluorimetry) using a double-ionophore technique. The maximal rate of ethyl isopropyl amiloride-sensitive H+efflux was significantly raised in leucocytes from the hypertensive subjects [75.3 ± 6.2 versus 48.8 ± 2.1 mmol/l per min in normotensives (mean ± s.e.m.);P< 0.001]. There was no difference in the affinity of the Na+—H+antiport for intracellular H+. Intracellular buffering power at different internal pH levels in the range 6.0-7.1 did not differ in the two groups. We conclude that one reason for the reported intracellular alkalinity and increased sodium content of leucocytes from hypertensive subjects in bicarbonate-free media could be an increased number of active Na+—H+exchangers or an increased turnover rate for each exchanger. A similar defect in vascular smooth muscle could account for the increased tone and thickening of the media. The abnormal maximal transport capacity of the leucocyte may be a useful membrane marker for future studies in human hypertension

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Five hundred and fifty-nine hypertensive outpatients with diastolic blood pressure between 95 and 110mmHg participated in this double-blind, placebo-controlled, multicenter study. Eligible subjects were randomly allocated to receive either clonidine (75 µg twice daily) or a placebo. After 4 weeks, 'responders' to treatment (diastolic blood pressure reduced to ≤ 90mmHg or by ≥10mmHg) were kept on monotherapy and checked at 4-weekly intervals for another 3 months. Non-responders were given 15 mg chlorthalidone and were also checked for a further 3 months. At the end of the first month, 54.2% of the subjects were responders to clonidine and 41.5% were responders to the placebo (P< 0.05 for both groups). Of the remaining patients, 69.0% became responders to clonidine plus chlorthalidone, whereas only 34.7% were responders to placebo plus chlorthalidone (P< 0.01 for both groups). Withdrawals from the study because of excessive diastolic blood pressure levels were about eight times less frequent among the subjects treated with clonidine, either alone or with chlorthalidone. Dry mouth was twice as frequent in the clonidine-treated patients, but there was no significant difference in the incidence of all side effects or the number of withdrawals from the study because of side effects between the two groups. We conclude that low-dose clonidine is effective in the treatment of mild or moderate hypertension. Clonidine-related side effects are still evident, but the overall tolerance profile for this reduced dosage of the drug appears to be favorable

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The relationship between the blood pressure level achieved through antihypertensive treatment and the incidence of coronary heart disease (CHD) was studied in 686 middle-aged hypertensive men. The patients studied came from a random population sample and were followed-up for 12 years, yielding a total of 6563 patient-years for the study. Eighty-seven patients suffered a non-fatal myocardial infarction or died from CHD. The incidence of CHD showed a J-shaped distribution in relation to achieved treated systolic and diastolic blood pressure levels. The incidence of CHD, adjusted for entry characteristics, age, serum cholesterol, blood pressure and smoking habits, decreased with reductions in blood pressure achieved through treatment, to a level of about 150/85 mmHg, below which the incidence rate again increased. This J-shaped pattern was also observed when data from patients with pre-existing signs or symptoms of ischemic heart disease at entry were excluded. Using a quadratic term as the best fit to the observed relationship between achieved treated diastolic blood pressure level and the incidence of CHD, a Cox regression analysis showed that the nadir of the J-shaped incidence curve was at a diastolic blood pressure value of 81 mmHg. There did not seem to be any association between the absolute size of the blood pressure reduction during treatment and the incidence of CHD. Although we cannot exclude the possibility that the increased incidence of CHD in patients with a low treated blood pressure is due primarily to pre-existing but subclinical ischemic heart disease, our findings indicate that an excessive lowering of blood pressure in hypertensive patients may be harmful. Therefore, until the optimal blood pressure goal on treatment has been better defined through specifically designed treatment studies, we suggest that a diastolic blood pressure level of 80-85 mmHg is the lowest that should be sought as a treatment goal in middle-aged, male hypertensive patients

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Precapillary resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were found to contain three inositol lipids and to produce five inositol phosphate peaks. These were assessed by a highly sensitive procedure which involved the separation of radiolabelled inositol-containing components by anion-exchange high-performance liquid chromatography. Basal levels of radiolabelled inositol lipids were found to be significantly increased in SHR at 5 weeks of age, and also increased at 12 weeks, although this was only statistically significant for glycerophosphoinositol. At 5 weeks of age, exposure to a maximal concentration of noradrenaline brought about a significant increase in lipid radioactivity in WKY and in glycerophosphoinositol and glycerophosphoinositol 4-phosphate in SHR. The levels of these lipids remained significantly raised in the SHR at this time. At 12 weeks of age, exposure to noradrenaline produced reductions in radioactivity associated with inositol lipids. These new levels were elevated in SHR and significant for glycerophosphoinositol 4-phosphate. Basal levels of four inositol phosphates were not different between the two rat strains at 5 weeks of age. Inositol 1,3,4-trisphosphate was only present at minute levels and could not be measured. At 12 weeks of age, basal radiolabelling of inositol phosphates was not different between the two strains. The application of noradrenaline caused age-dependent changes in arterial inositol-containing compounds in both strains, which resulted in increased levels of inositol 1,4,5-trisphosphate in young SHR and also in adult rats in which the blood pressure level had become established. This abnormality in inositol lipid second-messenger metabolism in genetically hypertension-prone rats provides a mechanism by which the levels of cytosolic free calcium, which have been found to be raised in essential hypertension, would be increased, and the implication of the inositol lipid system in this process suggests that this system may be important in the cellular processes at work in structurally altering the vascular wall when the blood pressure is rising

ISSN:0263-6352    

出版商:OVID    

年代:1990

数据来源: OVID