摘要:

ObjectiveIt has been suggested that the blood pressure elevation in borderline hypertension is caused by hyperreactivity to stress. We addressed the questions: are subjects with borderline hypertension hyperreactive to mental stress, and, if so, is this reflected in greater blood pressure responses during daily-life activities, and does non-specific pressor amplification by structural vascular changes contribute to reactivity changes?MethodsStandardized mental stress was performed during invasive monitoring in 54 borderline hypertensive subjects [systolic blood pressure (SBP) 140–160 or diastolic blood pressure (DBP) 84–95 mmHg, or both] and 20 normotensive control subjects (110–130/60–80 mmHg). Sixteen borderline hypertensive subjects had a cardiac index greater than the mean +1SD of the normotensive control group (hyperkinetic subgroup) and 38 borderline hypertensive subjects had a cardiac index below that level (normokinetic subgroup). Minimal vascular resistance in the forearm and calf was assessed by plethysmography. Ambulatory 24-h blood pressure was recorded.ResultsSubjects with hyperkinetic borderline hypertension had similar intra-arterial blood pressure levels to normokinetic borderline hypertensive subjects. Total peripheral resistance was lower in hyperkinetic borderline hypertensive than in normokinetic borderline hypertensive or normotensive control subjects. Hyperkinetic borderline hypertensive subjects had a significantly lower forearm minimal vascular resistance than normokinetic borderline hypertensive subjects. SBP and mean arterial blood pressure responses to stress were augmented in both borderline hypertensive subgroups. Hyperkinetic borderline hypertensive subjects also showed diastolic hyperreactivity in response to mental stress, in comparison both with normokinetic borderline hypertensive and with normotensive control subjects. During ambulatory blood pressure recording, hyperkinetic borderline hypertensive subjects had greater DBP and mean blood pressure increases from night to day than normotensive control and normokinetic borderline hypertensive subjects.ConclusionBorderline hypertension is characterized by pressor hyperreactivity to mental stress. In hyperkinetic borderline hypertensive subjects, stress hyperresponsiveness is also reflected by greater night-to-day blood pressure gradients during 24-h monitoring. Pressor hyperreactivity in hyperkinetic borderline hypertension is not explained by structural changes in the calf or forearm vasculature.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo investigate the effects of subpressor doses of angiotensin II (Ang II) on the progression of renal injuries in Dahl salt-sensitive (Dahl-S) rats with hypertension.MethodsRats were fed a high-salt (4% NaCI) diet and given an Ang II infusion (10 or 50 ng/kg per min, subcutaneously) for 4 weeks.ResultsThe plasma Ang II concentration achieved in the high-dose Ang II infusion was lower than that in low-salt (0.3% NaCI) normotensive rats. The Ang II infusion did not affect systolic blood pressure, cardiac hypertrophy or weight of thoracic aorta. However, the high-dose Ang II infusion increased proteinuria by 58%, enhanced the urinaryN-acetyl-β-D-glucosaminase index by 77% and reduced the glomerular filtration rate by 37%. The impaired renal function was associated with a progression of glomerulosclerotic lesions. Neither tubular nor arterial lesions were exacerbated. The infusion did not influence prostacyclin production or urinary cyclic GMP excretion.ConclusionA subpressor dose of Ang II infusion impairs renal function with progression of glomerulosclerosis, and these alterations may be due to increased susceptibility of the glomerulus in Dahl-S rats to Ang II-induced injuries. Such a mechanism might underlie a predisposition to hypertension-induced organ damage seen in Dahl-S rats with salt-induced hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveData concerning the effect of angiotensin II (Ang II) on plasma angiotensinogen levels are conflicting. Although Ang II is reported to stimulate the biosynthesis of angiotensinogen, plasma angiotensinogen is often depleted by renin when the level of renin, and therefore Ang II, increases. In the present study we used the Ang II subtype 1 (AT1) receptor antagonist losartan to investigate whether rising plasma Ang II levels stimulate angiotensinogen production to counteract the falling plasma angiotensinogen levels caused by increasing renin activity in plasma.MethodAngiotensinogen was measured in plasma from two previously reported studies in which 6-week-old stroke-prone spontaneously hypertensive rats (SHRSP) or Dahl salt-sensitive (Dahl-S) rats were fed high-salt diets (4 and 8% sodium chloride, respectively) for 10–12 weeks with or without losartan.ResultsAs reported previously, plasma renin was suppressed during the first 4 weeks of the high-salt diet but then paradoxically increased in both strains. When plasma renin increased, plasma angiotensinogen levels fell to 45 and 62% of the baseline value. The plasma renin concentration was negatively correlated with plasma angiotensinogen both in SHRSP and in Dahl-S rats (r = −0.76,P< 0.001 and r = −0.60,P< 0.001, respectively). In Dahl-S rats losartan treatment was associated with lower levels of plasma angiotensinogen but caused greater increases in plasma renin. When differences in renin were taken into account, plasma angiotensinogen levels were not different in losartan-treated and untreated Dahl-S rats. Similarly to Dahl-S rats, plasma angiotensinogen fell in SHRSP when renin increased, but SHRSP had higher plasma angiotensinogen levels during losartan treatment because plasma renin concentration was lower.ConclusionThe present study shows, in two strains of hypertensive rat, that an increase in plasma renin levels is associated with a fall in plasma angiotensinogen levels. Concurrent treatment with an Ang II AT1receptor antagonist does not augment this fall, except to the extent that renin rises further. The results provide no evidence for a significant tonic stimulatory effect of Ang II on plasma angiotensinogen levels.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo assess the renal benefits of a specific angiotensin II receptor antagonist, losartan, in diabetic rats with renal impairment.Design and methodsUninephrectomized streptozotocin diabetic spontaneously hypertensive rats (SHR) were randomly assigned to receive vehicle, or to receive losartan or captopril, or both, intraperitoneally via osmotic minipumps for 8 weeks.ResultsBlood pressure and urinary protein excretion in the diabetic SHR increased progressively during the experimental period. Both captopril treatment and losartan treatment completely blocked the development of hypertension in diabetic SHR. Simultaneous administration of captopril and losartan did not enhance the antihypertensive effects of losartan treatment or captopril treatment. Furthermore, losartan treatment, captopril treatment and losartan + captopril treatment all significantly decreased urinary protein excretion, urinary albumin excretion and serum creatinine to the same extent. These effects were sustained for the entire experimental period and were not associated with any significant changes in body weight, urine volume, urine sugar and urinary electrolytes excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. Losartan treatment, captopril treatment and losartan + captopril treatment all significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. Losartan treatment and captopril treatment both significantly attenuated the increase in heart weight: body weight ratio. The heart weight: body weight ratio in the losartan-treated group was significantly lower than in the captopril-treated group.ConclusionsThese results indicate that hypertension could accelerate diabetic renal impairment and that losartan has antihypertensive and renoprotective effects in this rat model. They also suggest that the antihypertensive and renoprotective effects of captopril treatment in this rat model are caused mainly by inhibition of angiotensin II production rather than stimulation of the kallikrein-kinin system or of vasodilator prostaglandins. The difference in potency between losartan treatment and captopril treatment to attenuate the increase in heart weight: body weight ratio might partly explain the existence in the heart of angiotensin-forming pathways, which are not dependent on angiotensin converting enzyme.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesAngiotensin converting enzyme (ACE) inhibitors reduce neointimal hyperplasia after balloon denudation, but the mechanisms are not completely understood. It has been demonstrated that nuclear oncogenes are induced in the vascular wall in the hours immediately after injury, and that the same genes are induced by angiotensin II in vascular smooth muscle cells. It has therefore been suggested that the effects of ACE inhibitors on the response of the vessel wall could be mediated by an inhibition of proto-oncogene expression.Methods and resultsSixteen New Zealand White rabbits were randomly assigned for histologic analysis to receive placebo (n = 9) or 1 mg/kg per day perindopril (n = 7). After treatment for 7 days balloon aortic injury was performed. The treatment was continued and the rabbits were killed 28 days after injury. In the perindopril group the neointimal cross-sectional area was significantly smaller than in the control group. Six untreated rabbits were used to assess the time course of proto-oncogene expression in the aortic wall after injury in the present model. After extraction, total aortic RNA was hybridized with myc, fos and jun probes. Based on the results, the effects of ACE inhibition on proto-oncogene expression were tested 1 h after balloon denudation. Accordingly, 24 rabbits were randomly assigned to pretreatment for 7 days with placebo or with 1 or 10 mg/kg per day perindopril (n = 8, for each group) and were killed 1 h after injury. Expression of c-mycwas not altered by pretreatment. However, 1 mg/kg per day perindopril induced significant reductions of 50% in c-junand 45% in c-fosexpression compared with control. No additional effect was obtained with the higher dose.ConclusionThe effect of ACE inhibition on intimal hyperplasia is associated with a reduction in early cellular events such as c-fosand c-junexpression. These results suggest that potent ACE inhibition at the time of vascular injury may be required to limit the hyperplastic response of the vessel wall.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective and designTo study the effects of blockade of the renin-angiotensin system on the development of hypertension and end-organ damage in hyporeninaemic deoxycorticosterone acetate (DOCA)-salt hypertensive rats, using an angiotensin II (Ang II) receptor antagonist (TCV-116) or an angiotensin converting enzyme (ACE) inhibitor (enalapril).MethodsDOCA-salt hypertensive rats were produced by uninephrectomy, implantation with DOCA pellets and 1% NaCI loading. TCV-116 (0.1 or 1 mg/kg) or enalapril (10 mg/kg) was given orally once a day from 3 to 6 weeks after the operation. Body weight, blood pressure, plasma renin and creatinine, urinary protein and blood urea nitrogen were measured. After 3 weeks' treatment, oedema and ±3-subtype benzodiazepine receptor binding in the brain were measured.ResultsThree weeks after the operation the blood pressure in the DOCA-salt hypertensive rats was approximately 200 mmHg, and the plasma renin concentration was lower than in sham-operated rats. However, after a further 3 weeks the renin concentration was slightly above the normal level, and this increase was accompanied by a decrease in body weight and increases in blood urea nitrogen, plasma creatinine, urinary protein and ±3-subtype benzodiazepine receptor binding in the cerebral cortex, and by brain oedema. Treatment with TCV-116 or enalapril prevented renal damage and decrease in body weight with little effect on blood pressure. Enalapril prevented brain oedema and the increase in benzodiazepine binding in the brain cortex, and 1 mg/kg TCV-116 prevented them markedly.ConclusionsAlthough the hypertension in DOCA-salt hypertensive rats is independent of the renin-angiotensin system, the degree of cerebral and renal damage is associated with the activity of the renin-angiotensin system and has little relationship with the blood pressure level.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective and methodExperimental evidence suggests that endogenous nitric oxide plays an important role in the homeostatic response to an increase in sodium intake. In the present study we evaluated the influence of a high sodium intake (1% NaCl as drinking water) on arterial hypertension induced by long-term (6–7 weeks) inhibition of nitric oxide synthesis [NG-nitro-L-arginine methyl ester (L-NAME), 75 mg/100 ml in the drinking fluid] in rats.ResultsTreatment with L-NAME induced progressive elevations in tail-cuff systolic blood pressure, but there were no differences between rats drinking tap water and rats drinking 1% NaCl. Direct measurement of blood pressure at the end of the treatment confirmed the hypertension and the lack of differences between the two groups treated with L-NAME. Metabolic studies performed at the end of L-NAME treatment showed a reduced glomerular filtration rate and elevated urinary excretion of immunoreactive endothelin in the two hypertensive groups treated with L-NAME. Drinking intake, diuresis and natriuresis were significantly higher only in the L-NAME group drinking 1% NaCI. Both groups treated with L-NAME showed an accelerated and increased diuretic and natriuretic response to an isotonic 0.9% NaCl load (2.5 ml/100 g body weight, intraperitoneally). At the end of the study ventricular hypertrophy was observed in both L-NAME groups.ConclusionThe present results indicate that the time-dependent elevation in blood pressure produced by long-term inhibition of nitric oxide production is not affected by an increased sodium intake. However, salt supplementation induced the development of a polyuria and polydipsia syndrome in rats treated with L-NAME. The elevated excretion of endothelin in both groups treated with L-NAME suggests the possible participation of endothelin in the development of L-NAME hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveWe have previously reported that low-density lipoproteins (LDL) isolated from patients with essential hypertension are more susceptible toin vitrooxidation than lipoproteins isolated from normotensive control subjects. In the present study we investigated the occurrence ofin vivoLDL oxidation in hypertensive patients.DesignThe presence of antioxidatively modified LDL autoantibodies was taken as a suitable index ofin vivoLDL oxidation because, after oxidative modifications, LDL express antigenic epitopes that elicit an immune response. The antibody titres were measured in plasma from untreated patients with newly diagnosed essential hypertension.MethodsAn enzyme-linked immunosorbent assay method was employed, using native LDL, Cu2+-oxidized LDL and malondialdehyde-derivatized LDL (MDA-LDL) as antigens. Human serum albumin and MDA human serum albumin were also used to monitor cross-reactivity with other oxidized molecules. The antibody titre was expressed as the ratio between anti-modified and anti-native antigen absolule values.ResultsThe patients with essential hypertension had an antibody ratio significantly higher than control subjects with respect to anti-Cu2+-oxidized LDL immunoglobulins G and M, and with respect to anti-MDA-LDL immunoglobulins G and M. A significant positive correlation was found between anti-MDA-LDL and anti-Cu2+-oxidized LDL antibody titres. The anti-MDA human serum albumin antibody titre was not different in the two groups of palients. An inverse correlation was detected between the anti-MDA-LDL immunoglobulin M titre and the age of the patients.ConclusionsThe results obtained are consistent with the view that, during the early phases of hypertension development, LDL undergoin vivooxidation that is mirrored by the generation of autoantibodies against epitopes of oxidized LDL. The oxidation process appears specific for LDL and might be relevant both for the progression of hypertension and for the development of the atherosclerosis that often complicates hypertension itself.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo investigate the alterations in erythrocyte ghost membrane microviscosity in essential hypertensive patients and to determine the relationship between these changes and the sodium-lithium countertransport activity as a sensitive marker of membrane function.SubjectsForty-three normolipidaemic essential hypertensive patients (23 treated, 20 untreated) and 27 normotensive controls were studied. Patients were attending the hospital hypertension clinic or a local general practitioner's surgery.MethodsErythrocyte sodium-lithium countertransport activity was measured. The Michaelis constant (Km) for extracellular sodium and maximal reaction velocity for sodium-lithium countertransport were measured in a subgroup consisting of 22 essential hypertensive patients and 11 normotensive controls. Erythrocyte membrane microviscosity was measured using fluorescence polarization anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH).ResultsThere was no significant difference in the fluorescence polarization anisotropy of DPH or TMA-DPH between normotensive and essential hypertensive patients. However, the fluorescence polarization anisotropy of TMA-DPH was increased significantly (reflecting increased membrane microviscosity) in hypertensive patients with a family history of hypertension compared with in patients without a family history of hypertension. The standard sodium-lithium countertransport activity was elevated in essential hypertensive patients compared with normotensive controls, and the Kmfor sodium was significantly lower in patients with a family history of hypertension than in patients without a family history of hypertension. Patients with a family history of hypertension were clustered, with significantly lower Kmfor sodium and higher TMA-DPH anisotropies than either hypertensive patients without a family history of hypertension or normotensive controls.ConclusionsThese findings suggest that a high membrane microviscosity affecting the outer region of the lipid bilayer is associated with altered sodium-lithium countertransport kinetics in a subgroup of essential hypertensive patients consisting of those with a family history of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

IntroductionWe hypothesize that in essential hypertension sympathetic nervous activity is related to the development of left ventricular hypertrophy, which can be regarded as a measure of the severity of hypertension.MethodsUsing spectral analysis, we studied the short-term variability in resting blood pressure and heart rate in essential hypertensive subjects. We measured blood over 10 min using a Finapres in 88 subjects after 20 min rest. We performed echocardiography to evaluate left ventricular hypertrophy and thereby identified three groups: 23 control subjects (group I), 29 hypertensive subjects (World Health Organization criteria) without left ventricular hypertrophy (group II) and 36 hypertensive subjects with left ventricular hypertrophy (group III). None had been treated for hypertension before the study.ResultsThe variability in blood pressure over a low-frequency period considered to be a marker of sympathetic activity was significantly increased in group II compared with groups I and III (analysis of covariance taking into account blood pressure and age). The variability in heart rate was similar in groups II and III, but both groups had a significantly reduced variability in heart rate compared with group I.ConclusionThese data, which examine globally, using a non-invasive method, all neurohormonal factors associated with the development of left ventricular hypertrophy, demonstrate that, in the time course of hypertension, low-frequency oscillations in blood pressure and heart rate are shifted to a lower level, presumably reflecting altered function of the sympathetic nervous system. We suggest that spectral analysis of blood pressure at rest in hypertensive patients can lead to complementary information to single measures of blood pressure and detect differences in the cardiovascular regulatory system.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID