摘要:

ObjectiveHealthy centenarians have a greater molar ratio of plasma insulin-like growth factor-1 to insulin-like growth factor binding protein-3 than that of aged subjects. We investigated the question of whether differences in mean arterial pressure and in this plasma ratio were related in healthy centenarians.Subjects and methodsWe studied 52 subjects in total, 30 aged subjects (70–99 years) and 22 healthy centenarians (> 100 years) to determine differences in mean arterial pressure, endothelial function and intracellular cation levels.ResultsIn the healthy centenarians, the molar ratio of fasting plasma insulin-like growth factor-1 to its binding protein-3 was significantly correlated with mean arterial pressure (r= −0.66,P< 0.001). Baseline (19.3 ± 1.5 versus 27.6 ± 2.2 μmol/l,P< 0.05) and L-arginine-stimulated percentage increases in the plasma total nitrate : nitrite ratio (67 ± 3.4 versus 48 ± 4.5%,P< 0.03) were greater in the healthy centenarians than in the aged subjects. An L-arginine bolus elicited an increase in forearm blood flow which was correlated with the percentage increase in the plasma total nitrate : nitrite ratio (r= 0.79,P< 0.001) and with the fasting erythrocyte magnesium concentration (r= 0.80,P< 0.001) in healthy centenarians. Both correlations remained significant (P< 0.01) after adjustment for sex, body mass index and the waist : hip ratio. Moreover, the fasting plasma molar ratio of insulin-like growth factor-1 to its binding protein-3 was correlated with the percentage increase in forearm blood flow (r= 0.59,P< 0.005) and with the percentage increase in the plasma total nitrate : nitrite ratio (r= 0.54,P< 0.009) in healthy centenarians. The centenarians had higher baseline total erythrocyte magnesium and lower calcium concentrations than the aged subjects. The addition of insulin growth factor-1 to the incubation medium increased the total intracellular erythrocyte magnesium content and decreased the calcium content in both groups of subjects. Nevertheless, the percentage increase in total erythrocyte magnesium (33 ± 3.8 versus 12 ± 3.4%,P< 0.03) and decline in intracellular calcium (17 ± 2.8 versus 8 ± 3.1%,P< 0.02) concentrations were greater in the healthy centenarians than the aged subjects.ConclusionIn healthy centenarians, insulin-like growth factor-1 may preserve endothelial function and modulate the intracellular cation content, thus contributing to a lower mean arterial pressure than that in aged subjects.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe arteries of aged spontaneously hypertensive rats (SHR) exhibit spontaneous electrical activity together with membrane depolarization. Vascular eicosanoid production is increased in SHR, which is further accelerated with aging. We tested the hypothesis that eicosanoids are involved in spontaneous electrical activity, membrane depolarization or both in mesenteric arteries of aged SHR.Design and methodsMembrane potentials were recorded with microelectrodes from the mesenteric arteries of aged (24 months and older) SHR, aged Wistar–Kyoto (WKY) rats and adult (6- to 8-month-old) SHR.ResultsThe membrane potential was less negative in aged SHR (−38.5 ± 0.9 mV) than in either aged WKY rats or adult SHR (−49.8 ± 0.5 and −47.2 ± 0.6 mV, respectively;P< 0.05 for both). Spontaneous electrical activity (5–20 mV, 1–7/min) was present only in arteries of aged SHR. Spontaneous electrical activity was not affected by phentolamine, atropine or tetrodotoxin, but was abolished by indomethacin, a cyclooxygenase inhibitor, and ONO-3708, a thromboxane A2/prostaglandin H2receptor antagonist. Furthermore, indomethacin and ONO-3708 hyperpolarized the membrane by about 5 mV in aged SHR but not in the other two groups. Spontaneous electrical activity was enhanced by a thromboxane A2analog and prostaglandin H2, and was abolished by a Ca2+antagonist, nicardipine, and Ca2+-free solution.ConclusionsThese findings suggest that cyclooxygenase-dependent eicosanoids contribute importantly to both spontaneous electrical activity and membrane depolarization, presumably through activation of the thromboxane A2/prostaglandin H2receptor, in mesenteric arteries of aged SHR, and that spontaneous electrical activity is mediated by a Ca2+influx through voltage-dependent Ca2+channels.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe tissue renin–angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypertension. In this study, we examined the gene expression of the tissue renin–angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats.Materials and methodsEight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin–angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis.ResultsSalt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin–angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet.ConclusionsThese results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin–angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin–angiotensin system.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo evaluate the influence of blood flow on measurements of regional sympathetic nerve activity by radiotracer methodology ([3H]noradrenaline).DesignTen healthy men were studied under two conditions of elevated forearm blood flow: mental stress (Stroop colour word conflict test) and an intra-arterial infusion of sodium nitroprusside.MethodsArterial blood pressure was measured invasively and forearm blood flow with strain-gauge plethysmography. Arterial and venous plasma adrenaline and noradrenaline were measured with high-performance liquid chromatography, and regional and total noradrenaline spillover were calculated.ResultsDuring mental stress, mean arterial pressure increased by 17%, heart rate by 16 beats/min, forearm blood flow by 117%, while forearm vascular resistance decreased by 44% (P< 0.001 for all). Sodium nitroprusside increased forearm blood flow dose-dependently, but elicited only minor effects on systemic haemodynamics. Mental stress increased arterial plasma noradrenaline by 52% (P< 0.001), and total body noradrenaline spillover by 75% (P< 0.001). During sodium nitroprusside infusion, arterial plasma noradrenaline increased only slightly and total body noradrenaline spillover was unaffected Forearm noradrenaline overflow increased from 5.4 ± 0.9 to 16.9 ± 2.6 pmol/min per l (P< 0.001) during mental stress and from 6.6 ± 0.8 to 16.9 ± 3.7 pmol/min per l (P< 0.001) during the second dose-step of sodium nitroprusside infusion. By intra-individual comparisons of forearm noradrenaline overflow increases during mental stress and during sodium nitroprusside infusion, with similar forearm blood flow increases, the flow dependence of forearm noradrenaline overflow was estimated. During mental stress, about 60% (median value, range 29–112%) of the increase in forearm noradrenaline overflow was attributed to the increase in forearm blood flow, whereas 40% was considered to reflect increased sympathetic nerve activity.ConclusionsThere seems to be a considerable flow dependence of the regional overflow of noradrenaline, that is, a component of simple wash-out of noradrenaline from the forearm tissues during vasodilation. However, the present results still indicate that sympathetic nerve activity in the forearm is increased during mental stress, justifying the radiotracer technique for semiquantitative measurements, also during vasodilation.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveIn hypertensive patients, exaggerated increases in vascular resistance and arterial blood pressure have been reported on changing posture from supine to upright. In this study we tested the hypothesis that in hypertensive subjects, upright posture induces an increase in the vasoconstrictor and pressor responses to physical exercise.Subjects and methodsWe studied 17 males with mild hypertension and 10 sex- and age-matched normotensives. Each performed three bouts of static handgrip at 30% maximum voluntary contraction for 2 min after 10 min of supine rest and, in sequence, after 10 min of sitting and 10 min of standing. Arterial pressure, heart rate and forearm vascular resistance were measured by Finapres and plethysmography, respectively.ResultsExercise posture did not affect the mean arterial pressure and heart rate responses to static handgrip. No significant differences in these responses were observed between the hypertensives and the normotensives in any posture. In the hypertensives (n= 12), forearm vascular resistance did not change significantly from resting values during supine and sitting static handgrip but increased significantly during standing static handgrip. In the normotensives, forearm vascular resistance did not change significantly from resting values during static handgrip in any posture. The forearm vascular resistance response to the standing static handgrip was significantly greater in the hypertensives than the normotensives. The algebraic sum of forearm vascular resistance responses to postural change from sitting to standing plus that induced by sitting static handgrip (i.e additive reflexes) was significantly less than the forearm vascular resistance response to the standing static handgrip (i.e. combined relexes), indicating a facilitatory interaction between exercise and orthostatic stimuli in hypertensives. In contrast, the algebraic sum of the heart rate responses to postural change from sitting to standing plus that induced by sitting static handgrip was significantly greater than the response to standing static handgrip, indicating an inhibitory interaction.ConclusionsIn hypertensive patients, physiological orthostasis causes an increased vasoconstrictor response to static exercise, but this is opposed by an inhibitory influence on the heart rate response, with the result that the pressor response to static exercise is unaffected by upright posture.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivePrevious studies have shown that as well as left ventricular hypertrophy, myocardial fibrosis develops early in rats with spontaneous hypertension (SHR). The present study was designed to investigate whether chronic treatment with the angiotensin II type 1 (AT1) receptor antagonist losartan modifies collagen type I metabolism and reverses left ventricular fibrosis in young SHR with left ventricular hypertrophy.DesignThe study was performed in 30-week-old normotensive Wistar–Kyoto (WKY) rats, untreated SHR and SHR treated with losartan (20 mg/kg per day, orally) for 14 weeks before they were killed.MethodsVentricular pro-α1(I) collagen messenger RNA was analyzed by Northern blot. Serum levels of the carboxy-terminal propeptide of procollagen type I (PIP) and the pyridoline cross-linked telopeptide domain of collagen type I (CITP) were determined by specific radioimmunoassays as markers of collagen type I synthesis and degradation, respectively. Collagen volume fraction was determined in the left ventricle by quantitative morphometry.ResultsCompared with WKY rats, SHR exhibited increased (P< 0.05) mean arterial pressure, pro-α1(I) collagen messenger RNA, PIP and left ventricular collagen volume fraction, and similar CITP values. After the treatment period, mean arterial pressure was higher (P< 0.05) in losartan-treated SHR than in WKY rats. Compared with untreated SHR, treated SHR showed no left ventricular hypertrophy and diminished (P< 0.05) values of mean arterial pressure, PIP and left ventricular collagen volume fraction. No changes in pro-α1(I) collagen messenger RNA and CITP values were observed with treatment in SHR. No significant differences in the left ventricular collagen volume fraction were observed between treated SHR with normal blood pressure and treated SHR with abnormally high blood pressure at the end of the treatment period.ConclusionsThese results suggest that chronic AT1blockade with losartan decreases the post-transcriptional synthesis of fibril-forming collagen type I molecules in young SHR. This effect may be involved in the ability of this drug to reverse left ventricular fibrosis in young rats with genetic hypertension. Apart from its antihypertensive action, other mechanisms may mediate the antifibrotic effect of losartan in this animal model.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine whether type A behavior, which is associated with a risk of coronary heart disease, affects left ventricular hypertrophy in patients with essential hypertension.DesignCross-sectional study of 88 untreated patients with mild to moderate essential hypertension (33 men, mean ± SEM age 54 ± 1 years).MethodsWe measured the type A behavior score using a standardized questionnaire, left ventricular mass index using M-mode echocardiography and 24 h mean ambulatory blood pressure (recorded every 30 min). Beat-to-beat blood pressure was also measured using a Finapres device in patients at rest and during mental stress (counting backward) to determine the blood pressure response to stress.ResultsThe left ventricular mass index was correlated with the type A behavior score (r= 0.214,P< 0.05), age (r= 0.266,P< 0.05), 24 h mean systolic and diastolic blood pressures (r= 0.391,P< 0.001, andr= 0.382,P< 0.001, respectively), systolic blood pressure both at rest and during stress (r= 0.255,P< 0.05, andr= 0.215,P< 0.05, respectively), and the variability of both systolic and diastolic blood pressures at rest (r= 0.253,P< 0.05, andr= 0.321,P< 0.01, respectively). Stepwise multiple linear regression analysis demonstrated that age was associated with an increase in the left ventricular mass index for both sexes (P= 0.004 for males,P= 0.003 for females). The type A behavior score predicted a greater increase in left ventricular mass index in men (P= 0.018) but not in women. The 24 h mean systolic blood pressure was associated with a greater increase in left ventricular mass index in women (P< 0.001) but not in men.ConclusionType A behavior is an independent risk factor for left ventricular hypertrophy in male patients with essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveAcute and prolonged effects of L-arginine on systemic and renal hemodynamics and on renal pathological changes were examined in 85-week-old spontaneously hypertensive rats (SHR).ResultsAfter 3 weeks of L-arginine administration (n= 9; 2 g/l in drinking water), mean arterial pressure remained unchanged, although the cardiac index increased (187 ± 26 versus 263 ± 15 ml/min per kg;P< 0.05) and total peripheral resistance decreased (1.15 ± 0.18 versus 0.67 ± 0.06 AU;P< 0.05); the glomerular filtration rate increased (0.41 ± 0.07 versus 0.79 ± 0.07 ml/min;P< 0.01). Control untreated, aged SHR (n= 10) demonstrated severe nephrosclerosis histologically, but those treated with L-arginine demonstrated a markedly reduced glomerular injury score (164 ± 22 versus 83 ± 9;P< 0.005), and their urinary protein excretion (39 ± 5 versus 19 ± 5 mg/100 g body weight per day;P< 0.05) and serum creatinine concentration (1.4 ± 0.1 versus 0.9 ± 0.1 mg/dl;P< 0.05) diminished. Intravenous L-arginine (300 mg/kg body weight) given to untreated SHR reduced mean arterial pressure, increased the cardiac index (+98 versus +1%;P< 0.05) and decreased total peripheral resistance (+56 versus +13%,P< 0.005); however, these variables remained unchanged after 3 weeks of L-arginine treatment.ConclusionsThree weeks of treatment with L-arginine improved systemic hemodynamics, renal function and renal histologic changes in aged SHR with naturally occurring nephrosclerosis. These data provide an important insight into the pathophysiology of nephrosclerosis in hypertension and with aging, which is seen clinically.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe primary objective of this double-blind, parallel-group, placebo-controlled, multicentre study was to compare the antihypertensive efficacy of one versus two daily doses of eprosartan, a novel nonbiphenyl, nontetrazole angiotensin II receptor antagonist, in 243 patients with mild to moderate hypertension (sitting diastolic blood pressure ≥ 95 to ≤ 114 mmHg).Patients and methodsThe patients were randomized to titrated doses of eprosartan at 400–800 mg once a day, eprosartan at 200–400 mg twice a day, or placebo, with the incremental dose titrated over a 9-week period. Patients reaching target blood pressure (sitting diastolic blood pressure of ≤ 90 mmHg) continued the fixed-dose treatment for 4 weeks. The primary efficacy measure was the mean change in trough sitting diastolic blood pressure from baseline to the study endpoint, determined on an intent-to-treat basis.ResultsBy the end of the study, eprosartan had significantly reduced mean trough sitting systolic and diastolic blood pressure relative to baseline and to placebo. The mean ± SD change from baseline in diastolic pressure was −9 ± 8.4 mmHg for the single daily dose, −9 ± 8.5 mmHg for two doses a day and −4 ± 8.1 mmHg for placebo (P< 0.0001 versus placebo for both eprosartan regimens). Similarly, both eprosartan regimens significantly reduced mean trough standing systolic and diastolic blood pressure. At the end of the study, the response rate in the single daily dose group (46.8%) was significantly higher than in the placebo group (25.6%). There were no significant differences between the treatment groups in the number of patients whose blood pressure responded to treatment; 41.7% of those taking eprosartan once a day and 44.4% of those taking eprosartan twice a day, and who responded to treatment, were maintained on their original starting doses. The total daily dose required to achieve target blood pressure was comparable, whether eprosartan was administered once or twice a day. Both eprosartan regimens were well tolerated and the incidence of adverse events with eprosartan was similar to that of placebo.ConclusionsThese results demonstrate that there was no significant difference in antihypertensive efficacy or tolerance between eprosartan taken in one or in two daily doses. Both dosing regimens provided significant and clinically meaningful reductions in blood pressure that were superior to placebo. Eprosartan in a single daily dose was shown to be an effective antihypertensive agent. Because of the good adverse-effect profile and the simplicity of a single daily dose, eprosartan has the potential to improve patient compliance.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo compare the therapeutic coverage and safety of amlodipine and perindopril in patients with mild to moderate hypertension (diastolic blood pressure ≥ 90 mmHg and ≤ 109 mmHg).DesignA double-blind, randomized, parallel-group, multicentre study.MethodsFollowing a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either amlodipine at 5–10 mg once a day or perindopril at 4–8 mg once a day, for 60 days. Trough : peak ratios were calculated by two different methods (global and individualized approaches) from 24 h ambulatory blood pressure recordings made after the placebo period and after the active treatment period. Residual lowering of blood pressure after single-blind, single-dose omission was also investigated with further 24 h ambulatory blood pressure monitoring. Safety assessments were made throughout the study.ResultsThe placebo-adjusted, global, diastolic blood pressure trough : peak ratio was 0.80 in the amlodipine group (n= 47) and 0.81 in the perindopril group (n= 49) in an intent-to-treat analysis. The corresponding global systolic blood pressure trough : peak ratio was 0.83 for amlodipine and 0.68 for perindopril. Individual trough : peak ratios were non-normally distributed. Mean (± SD) individual trough : peak ratios (intent-to-treat analysis) for diatolic blood pressure were 0.50 ± 0.69 for amlodipine (median 0.42) and 0.15 ± 3.27 for perindopril (median 0.33). In the per protocol analysis, the corresponding values were 0.50 ± 0.72 (median 0.34) for amlodipine and 0.01 ± 3.90 for perindopril (median 0.21). Both treatments produced comparable decreases in clinic systolic and diastolic blood pressure between days 0 and 60. Forty-eight hours after the last dose, both systolic and diastolic blood pressure were lower in amlodipine-treated patients than perindopril-treated patients. Amlodipine and perindopril were generally well tolerated. The most frequently reported adverse event was leg oedema in amlodipine-treated patients (19.1%), and coughing in perindopril-treated patients (14.3%).ConclusionsThese results showed no statistically significant difference in trough : peak ratios between amlodipine and perindopril. However, the ambulatory blood pressure trough : peak ratios showed very large variations. Determination of trough : peak ratios by the conventional approach or by an individual approach can yield disparate values. After omitting one dose, a condition imitating noncompliance, blood pressure was more effectively controlled with amlodipine than with perindopril.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID