ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo answer two specific questions concerning the possible role played by the angiotensin II receptor AT1 B (AT1 B) locus in genetic hypertension. First, do alleles at the AT1 B locus cosegregate with blood pressure in F2populations in the rat and, if so, is this due to AT1 B or a closely linked quantitative trait locus (QTL)? Secondly, are there any significant nucleotide differences between the coding regions of the AT1B gene of the inbred Dahl salt-sensitive (SS/Jr) strain and various control strains, or between the Lyon hypertensive (LH) strain the Lyon normotensive (LN) strain?DesignThe first objective was achieved by studying several F2rat populations and by analyzing DNA markers around the AT1B locus. The second objective was accomplished by amplifying the AT1B coding regions by polymerase chain reaction from the genomic DNA, and by sequencing the relevant coding regions of the AT1B genes.Results:In two F2populations involving the SS/Jr rat, AT1 B cosegregated only weakly with systolic blood pressure. Also, nucleotide differences resulting in conservative changes in three amino acids were detected between the coding region of the SS/Jr AT1B allele and the AT1B alleles of the several control strains. No nucleotide differences were found in the coding regions of the AT1B alleles between the LH and LN strains.Conclusion:There appeared to be a QTL which had a minor effect on blood pressure, located near the AT1B locus on rat chromosome 2. However, the AT1 B gene itself is not supported as the candidate gene for causing blood pressure differences, because no nucleotide changes in the coding region that were functionally meaningful or concordant with the cosegregation analysis were detected.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate the role of Na+-Ca2+exchange in the regulation of cytosolic free Ca2+and the pathogenesis of primary hypertension.Method:Cytosolic free Ca2+([Ca2+]i) in cultured vascular smooth muscle cells from normotensive and spontaneously hypertensive rats of the Münster strain was measured using the fluorescent dye fura-2 after inhibition of Na+,K+ATPase by ouabain and after addition of angiotensin II.Results:[Ca2+]ishowed a rapid increase together with a depolarization of membrane potential as measured by merocyanine 540. The ouabain-induced increase in [Ca2+]iwas blocked in Ca2+-free medium and by nifedipine, but incubation with the inhibitor of the Na+-Ca2+exchange, NiCl2, did not diminish the effect of ouabain. Likewise, in Na+-free medium the response to ouabain was not suppressed. The angiotensin II-induced changes in [Ca2+]iwere diminished in Ca2+-free medium and by nifedipine, but enhanced by NiCl2.Conclusion:The increase in [Ca2+]iafter Na+,K+ATPase inhibition is not due to a modulation of Na+-Ca2+exchange, but to a Ca2+influx through Ca2+channels. Changes in Na+-Ca2+exchange caused by Na+,K+ATPase inhibition may not play an important role in vascular smooth muscle cells of spontaneously hypertensive rats.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo assess the role of dietary sodium with or without chloride on the development of hypertension and left ventricular hypertrophy.Methods and results:Forty-nine male Sprague-Dawley rats with two-kidney, one clip hypertension were fed three different diets for 4 weeks after clipping: free access to sodium chloride, sodium citrate or sodium-free diet. Sham-operated rats were used as controls. The final conscious systolic arterial pressure was similar in all hypertensive groups, regardless of diet. A similar increase in left ventricular mass was observed in the rats on the sodium chloride and sodium citrate diets, whereas left ventricular hypertrophy was strikingly attenuated in the rats on the sodium-free diet.Conclusion:Dietary sodium restriction prevented the development of left ventricular hypertrophy without affecting consistently the final level of hypertension. Also, the anion associated with sodium had no influence on the level of arterial pressure and left ventricular mass when compared with rats maintained on sodium chloride. It is suggested that dietary sodium itself might be an important modulator of the left ventricular response to hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that chronic exposure to psychosocial stress, alone or in combination with elevated levels of dietary salt, leads to hypertension and cardiac pathology in a susceptible strain of rats.Design and methods:In four experiments, borderline hypertensive rats, maintained on normal or high-salt diets, were exposed to 14–16 weeks aggregation in a colony housing or in larger breeder cages. Pulsatile blood pressure was measured once a week in unrestrained male rats by pressure telemetry. Direct carotid pressures of the aggregated rats and of control rats were measured before they were killed; at necropsy cardiac and adrenal weights and ventricular design were determined.Results:Despite continuous fighting, their weekly measured blood pressures remained stable; no differences in final carotid pressures between experimental and control rats were found. Rats from three aggregations showed significant increases in left and right ventricular and adrenal weights.Conclusion:No hypertension developed in any aggregation, although most of the rats showed signs of perceived stress (significantly reduced weight gain, enlarged adrenals and a large number of body wounds). Cardiac hypertrophy did ensue, possibly reflecting increased physical activity or intermittent increases in sympathetic activity, or both.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectivePressure-diuresis-natriuresis relationships were compared in rats made transgenic by implantation of the mouse salivary gland renin gene [TGR(mRen-2)27 rats] and Sprague-Dawley/Hannover rats to determine whether resetting of renal function contributes to the development of hypertension in these rats.Methods:Differences in the neural and hormonal background were minimized by denervating the kidney and holding plasma vasopressin, aldosterone, cortisol and norepinephrine levels constant by intravenous infusion.Results:In Hannover rats (n=9), urine flow and sodium excretion increased from 26.4±6.2 to 86.8±8.6 μl/min per g kidney weight and from 5.1±0.8 to 15.3±1.0 μol/min per g kidney weight as renal perfusion pressure (RPP) was increased from 107 to 153mmHg. The renal blood flow (RBF) and glomerular filtration rate (GFR) were well-autoregulated and averaged 6.6 and 1.5 ml/min per g kidney weight throughout the range of pressures studied. In TGR (n = 10), urine flow and sodium excretion increased from 30.0±6.1 to 59.±7.2 μl/min per g kidney weight and from 3.8±0.9 to 8.5±1.3 μmol/min per g kidney weight in response to an elevation in RPP from 170 to 212mmHg. The RBF and GFR were about 20% lower in TGR than in Hannover rats and averaged 4.1 and 1.0 ml/min per g kidney weight, respectively.Conclusion:The results show that the pressure-diuresis-natriuresis relationship is shifted to higher pressure levels in TGR and that this is associated with enhanced tubular reabsorption. The reduced excretory function in TGR is intrinsic to the kidney, but the extent to which these changes are related to a relative overexpression of the renin-angiotensin system within the kidney, or are secondary to hypertensive renal structural changes, remains to be determined.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveThis long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo.Methods:One hundred and twelve older (±60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up.Results:At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (±SD) averaged 176±12/86±7 mmHg and 24-h SBP/DBP 151 ± 15/81 ± 10mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo. After the 112 patients had received placebo for 1 year (median), clinic SBP/DBP fell by 6.6±15.9 (P<0.001)/1.4±7.4 (P=0.06)mmHg and 24-h SBP by 2.4±10.7mmHg (PConclusions:These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo. Like those using conventional sphygmomano-metry, long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To assess the effects of omega-3 (n-3) fatty acid supplementation on blood pressure and plasma lipids in hypertensives treated with diuretics or beta-blockers.Design:Double-blind placebo-controlled cross-over trial consisting of a 4-week run-in phase and two 6-week intervention phases.Patients:A total of 43 patients of either sex taking a beta-blocker only (n = 29), a diuretic only (n = 3) or a beta-blocker plus diuretic (n=11) for hypertension were recruited from general practice. One patient from the latter group was withdrawn.Methods:Seated blood pressure was measured every 2 weeks in the clinic with a Dinamap. After the run-in phase, participants were randomly assigned to take a supplement of either Omacor (85% n-3 fatty acid concentrate) or corn oil (four 1-g capsules/day) for 6 weeks, after which they crossed over to the other supplement. Fasted blood samples were taken at the end of each phase for lipid analysis.Main outcome measures:The within-individual differences in systolic and diastolic pressure and plasma lipids between Omacor and corn oil treatment.Results:Systolic/diastolic blood pressures measured during the run-in phase were normal (132±2/76±1 mmHg, n = 42) but decreased further with n-3 fatty acid supplementation. The mean within-individual difference in blood pressure compared with corn oil supplementation was 3.1 ± 1.0/1.8±0.6 mmHg (P<0.01). This was accompanied by a 21% reduction in plasma triglycerides (P< 0.01) and a 15% increase in high-density lipoprotein-2 cholesterol (P< 0.01) but there were no significant differences in total or low-density lipoprotein cholesterol.Conclusion:The antihypertensive and hypotriglyceridaemic effects of n-3 fatty acid supplementation seen in the present study suggest that it may be a useful adjunct to antihypertensive therapy with beta-blockers or diuretics.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:The nitric oxide (NO) system is abnormal in essential hypertension and the response of the forearm vascular bed to local intra-arterial infusions of NG-monomethyl-L-arginine (L-NMMA) is diminished in patients with untreated essential hypertension. Animal data suggest that treatment of hypertension may restore normal NO-mediated responses. We have prospectively examined the effect of standard antihypertensive therapy on the responsiveness to local intra-arterial infusions of L-NMMA in 18 newly diagnosed hypertensive patients.DesignThis was a double-blind, randomized, parallel-group study. Patients were randomized to treatment with 10mg enalapril daily, 5mg amlodipine daily or matched placebo for 6 weeks (with dose titration after 2 weeks if necessary).Methods:Forearm blood flow during direct infusion into the brachial artery of L-NMMA (1, 2 and 4 μmol/min) was measured using venous occlusion plethysmography at the beginning and end of the 6-week treatment period.Results:Both enalapril and amlodipine reduced blood pressure significantly compared with placebo. After 6 weeks of antihypertensive therapy, forearm blood flow (±SEM) in response to the maximum dose of L-NMMA (4 μmol/min) was reduced by 54.8 (6.9)% (P= 0.012), 58.9 (7.0)% (P= 0.016) and 33.1 (3.0)% (P=0.17) in the enalapril, amlodipine and placebo groups, respectively. There was no significant difference between enalapril and amlodipine treatment groups.Conclusions:The forearm arterial responsiveness to L-NMMA in newly diagnosed patients with essential hypertension returns to normal with normalization of blood pressure by antihypertensive drugs with different modes of action. It remains to be determined whether this phenomenon is a consequence of the change in pressure per se or a result of the action of either drug by a common or separate mechanism.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo investigate whether there are definable subgroups of patients with essential hypertension who respond specifically to particular antihypertensive drugs.DesignRandomized cross-over comparison of the antihypertensive effect of 50 mg atenolol per day, 10 mg lisinopril per day and 20 mg nifedipine retard twice a day. Ambulatory blood pressure monitoring was used to assess the blood pressure level both for recruitment and at the end of each treatment period. The treatment periods lasted 4 weeks and were preceded by 4 weeks of placebo.Patients:Seventy-two untreated hypertensive patients with a mean age of 52 (SD 8.4) years were recruited from six general practices and from the hospital outpatient clinic. Sixty-eight patients completed the trial.Main outcome measures:To assess the within-patient correlations among the blood pressure responses to each drug and explore the possible role of simple characteristics, such as the initial blood pressure, plasma renin concentration and age, in identifying the responders to a particular drug.Results:Systolic/diastolic blood pressure fell significantly with each agent (P<0.001): atenolol reduced it by 16.3±13.3/9.9±8.8, lisinopril by 14.8±15.0/9.4±9.1 and nifedipine by 11.6±12.3/6.7±8.3 mmHg. There was a low degree of correlation between the changes in blood pressure with the three drugs in individual patients. With each drug there was a small percentage (8.9–14.7%) of non-responders. The initial level of systolic blood pressure was weakly correlated with the antihypertensive effect of nifedipine (r=0.47,P<0.001) and plasma renin concentration was related to the effect of atenolol (r=0.32,P<0.01). Age did not predict the blood pressure response to any agent.Conclusions:The low level of the correlation between the blood pressure changes with the three drugs suggests that different mechanisms may be involved in the aetiology of essential hypertension. Plasma renin concentration and the initial level of systolic blood pressure contribute only weakly to the identification of responders to the three drugs.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID