ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo describe several emerging concepts regarding the biosynthesis, metabolism and biological roles of adenosine and to illustrate the possible significance of these ideas to vascular biology by proposing a hypothesis pertaining to the role of erythrocyte-derived adenosine deaminase in vaso-occlusive diseases associated with damaged erythrocytes.Multiple pathways for adenosine formationThree pathways of adenosine biosynthesis have been well established: the intracellular ATP pathway, the extracellular ATP pathway and the transmethylation pathway. A fourth pathway that has received relatively little attention, but could be particularly important in vascular smooth muscle, is the cyclic AMP-adenosine pathway. This pathway involves the extracellular or intracellular metabolism, or both, of cyclic AMP to AMP and hence to adenosine. Our recent experiments in cultured vascular smooth muscle cells, isolated vascular beds and intact animals support the existence of the cyclic AMP-adenosine pathway. Together these four pathways of adenosine formation should assure pharmacologically active levels of vascular adenosine.Antivaso-occlusive actions of adenosineThe overall pharmacologic profile of adenosine suggests that this nucleoside functions to protect vascular beds from vaso-occlusive events. In this regard, some well known effects of adenosine include vasodilation, release of nitric oxide from vascular endothelial cells and inhibition of platelet aggregation, platelet adhesion, neutrophil-endothelial interactions, renin release and noradrenergic neurotransmission. Moreover, studies indicate that adenosine also releases nitric oxide from cultured vascular smooth muscle cells and inhibits vascular smooth muscle cell growth. Thus, any condition that reduces the levels of adenosine in the blood vessel wall or blood vessel-blood interface might predispose toward vaso-occlusive events.Damage to erythrocytes reduces adenosine levelsAdenosine deaminase rapidly metabolizes adenosine to inosine, which lacks antivaso-occlusive properties. Because erythrocytes are generously endowed with adenosine deaminase, any condition that damages erythrocytes will cause leakage of adenosine deaminase from erythrocytes directly onto the blood vessel wall, thus diminishing local vascular levels of adenosine. Experiments using dimethyl sulfoxide-induced hemolysis have confirmed the hypothesis that erythrocyte-derived adenosine deaminase can reduce adenosine levelsin vivo.Hypothesis: the role of erythrocyte-derived adenosine deaminase in vaso-occlusive diseasesBecause multiple biosynthetic pathways maintain pharmacologically active levels of adenosine within the blood vessel wall and adenosine exerts a number of antivaso-occlusive effects, release of adenosine deaminase from erythrocytes may increase the risk for vaso-occlusive events.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo study blood pressure adaptation in relation to age and sex. In a subsample, laboratory blood pressure measurements were compared with ambulatory daytime blood pressure measurements to determine the degree of agreement between the two methods. The night-time blood pressure reduction was analysed as a function of blood pressure status, age and sex.DesignA cross-sectional study in 469 healthy volunteers, aged 23–82 years, stratified for age, sex and educational level.MethodsLaboratory blood pressure was measured automatically (Dinamap 8100) five times during a 20 min recording session. Cardiovascular events in the medical history were identified in order to treat the cardiovascular event-free group separately in subsequent analyses. Within 3 weeks after laboratory blood pressure measurement, ambulatory blood pressure was measured for 24h in 135 volunteers from the main study.ResultsBoth diastolic and systolic blood pressure varied markedly in a single measurement session as a function of age, independent of mean pressure level. After 15 min no further blood pressure decrease was observed. On the basis of the average of the final two blood pressure measurements, 18.8% of the subjects were in the hypertensive range (WHO/ISH guidelines). Ambulatory blood pressure measurements were in accord with earlier findings and correlated 0.74 and 0.73 with laboratory diastolic and systolic blood pressure, respectively, but weighted k values indicated only moderate agreement (0.42 and 0.51). Women showed a more profound reduction in cnight-time blood pressure than did men.ConclusionsThere is a substantial change in blood pressure during a single measurement session which is greater in older age groups. The moderate agreement between the two methods of blood pressure measurement supports the notion that blood pressure measured in a single session has limited generalizability to average daytime levels in a population sample.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo investigate the diurnal blood pressure curve in healthy normotensive children. Thirty-one children were re-examined after a median interval of 123 days in order to study the reproducibility of the diurnal profile.SubjectsTwenty-four-hour ambulatory blood pressure monitoring and conventional blood pressure readings were obtained in 228 normotensive children, whose ages ranged from 6 to 16 years and of whom 116 were boys and 112 girls.ResultsThe conventional blood pressure averaged 99±11/57±9mmHg in boys and 98±12/56±9mmHg in girls (means±SD); the corresponding 24 h pressures were 111±7/66±5mmHg and 109±7/65±5mmHg, respectively. Of the children, 83% had a significant diurnal blood pressure rhythm for systolic pressure and 89% for diastolic pressure. The nocturnal blood pressure fall was normally distributed, averaging 12.0±6.3mmHg systolic and 14.2±5.9mmHg diastolic. There was no evidence for a bimodal distribution. The amplitude of the diurnal blood pressure curve, determined by the Fourier approach, was positively skewed with a mean of 12.5±4.2mmHg for systolic and 14.0±4.1mmHg for diastolic blood pressure. The daily blood pressure maximum occurred at 1344±4h 46 min for systolic and 1321±4h 22min for diastolic blood pressure. For systolic blood pressure the cumulative sum (cusum)-derived circadian alteration magnitude was 1.7±6.2mmHg higher in boys than in girls, whereas the cusum plot height was also 7.3±27.0mmHg x h higher in male subjects. The repeatability coefficient (2 SD of the difference between paired recordings, expressed as a percentage of nearly maximal variation) was 80% for the conventional systolic pressure and 40% for the conventional diastolic blood pressure. The repeatability coefficients for the ambulatory blood pressure levels varied from 32 to 45% and for the parameters describing the diurnal blood pressure profile from 42 to 78%.ConclusionA significant diurnal blood pressure rhythm is observed in most normotensive children and adolescents. There is no evidence for a bimodal distribution of the nocturnal blood pressure fall. The reproducibility of the parameters of the diurnal blood pressure curve tended to be less than that of the ambulatory blood pressure level. Thus, one 24 h recording is probably insufficient to characterize a child's diurnal blood pressure profile fully.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo define whether a diurnal rhythm of peripheral resistance exists in normotensive and hypertensive subjects, has any relationship with that of blood pressure and differs in dipper and non-dipper hypertensives.Design and methodsForty-three subjects (13 normotensives and 30 mild-to-moderate essential hypertensives) confined for 24 h to bed were included. Blood pressure was recorded for 22 h at 15 min intervals, plethysmographic forearm flow was simultaneously measured and forearm resistance calculated. The analysis was performed for the whole 22 h period and for three 4h truncated periods, two of certain wakefulness and one of certain sleep.ResultsA circadian rhythm of forearm resistance was shown in the normotensives, paralleling that of blood pressure. All the normotensives were dippers, with a nocturnal blood pressure dip (systolic/diastolic) of −4.5/-6.0%. In the hypertensives, the day/night blood pressure trends were not homogeneous: 21 showed higher blood pressure values during waking time, with a trend quite similar to that of the normotensives, whereas the other nine were non-dippers. Resistance was lower during sleep than during waking both in the normotensives and in the dipper hypertensives, whereas in the non-dippers it was higher during sleep.ConclusionsA sleep/waking rhythm of peripheral resistance with the highest values during daytime and the lowest during night-time does exist in normotensive as well as in the majority of hypertensive subjects resting continuously in bed, and therefore is largely independent of physical activity. Only in a minority of hypertensive patients are higher values of peripheral resistance present during sleep.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition.MethodsIn 14 renovascular hypertensive patients (age 43.8±2.1 years, mean±SEM, clinic blood pressure 173.6±3.7mmHg systolic and 109.0±2.0mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty.ResultsThe 24 h average systolic and diastolic blood pressures were 146.4±5.7 and 97.5±3.6mmHg in renovascular and 144.3±1.2 and 98.0±2.2mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and −18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardla.ConclusionsNocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo investigate a model of experimental hypertension that exhibits severe hypertrophy of small blood vessels but in which deoxycorticosterone acetate (DOCA) and salt are absent: the one-kidney, one clip model of Goldblatt renovascular hypertension, which is non-renin-dependent, and compare it with the renin-dependent two-kidney, one clip Goldblatt hypertensive rat, in which additionally vascular hypertrophy is less severe.MethodsEndothelin-1 gene expression in blood vessels and in the heart was examined by Northern blot analysis.ResultsAfter 2 or 4 weeks of application of the silver clip to unilaterally nephrectomized rats, the aorta and mesenteric arteries exhibited a significant increase in the intensity of the 2.3kb band corresponding to hybridization with endothelin-1 messenger RNA (mRNA) in comparison with results obtained in control unilaterally nephrectomized rats. No increase was noted in the blood vessels of the two-kidney, one clip hypertensive rat at 2 or 4 weeks, but significant increases were found at 8 weeks in aorta, but not in mesenteric arteries. Cardiac abundance of endothelin-1 mRNA was also increased in ventricles and in the left atria of one-kidney, one clip hypertensive rats, but only in the late phase (at 8 weeks) in two-kidney, one clip hypertensive rats.ConclusionBecause one-kidney, one clip hypertensive rats presented severe vascular hypertrophy whereas two-kidney, one clip hypertensive rats only did so in the late phase of hypertension, these results lend further support to there being a relationship between vascular hypertrophy and endothelin-1 vascular overexpression in experimental models of hypertension. They also demonstrate that enhancement of the expression of endothelin-1 gene in blood vessels and in the heart of hypertensive rats may occur in the absence of exposure to DOCA and salt, and that endothelin-1 gene overexpression in experimental hypertension occurs early in non-renin-dependent, volume-expanded models such as the one-kidney, one clip or the DOCA-salt hypertensive rat, but only in the progressively non-renin-dependent late phase of the initially renin-dependent volume-contracted two-kidney, one clip hypertensive rat.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveElevated blood pressure is a common effect of aging that results from alterations in the calcium (Ca2+) homeostatic mechanisms in vascular smooth muscle cells. The sarcoplasmic reticulum is a primary subcellular organelle involved in Ca2+homeostasis in vascular smooth muscle. This study was therefore undertaken to delineate possible age-associated changes that occur in the sarcoplasmic reticulum Ca2+homeostatic mechanisms.MethodsRelaxation rates after phenylephrine-induced contractions in aortic smooth muscle from rabbits of increasing age were evaluated in the presence of thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor. In addition, electron probe X-ray microanalysis (EPMA) was used to analyze the total calcium content of the sarcoplasmic reticulum and cytosol in aortic smooth muscle from rabbits of various ages.ResultsThe relaxation rate of rabbit aorta contracted with phenylephrine declined with age, the decline being progressively reduced when Ca2+uptake by the sarcoplasmic reticulum was abolished by thapsigargin. EPMA measurements demonstrated an increased cytosolic calcium content and possibly reduced sarcoplasmic reticulum calcium content in arteries from older animals compared with arteries from juvenile animals.ConclusionsReuptake of Ca2+by the sarcoplasmic reticulum is necessary for optimal relaxation of rabbit aorta after a maximal, agonist-induced contraction. The present data suggest that impaired activity of the sarcoplasmic reticulum Ca2+pump associated with aging may contribute to the increased cytosolic calcium content and elevated resting tone of aortic smooth muscle obtained from older rabbits.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveWe studied the dose–response effects of acute administration of the selective A1adenosine receptor agonist 2-chloro-N-6-cyclopentyladenosine (CCPA), the selective A2Aagonists 2-hexynyl-5‘-N-ethylcarboxamido-adanosine (2HE-NECA) and 2-[4-(2-carboxyethyl)phen-ethylamino]-5’-N-ethylcarboxamidoadenosine (CGS 21680) and the non-selective agonistN-ethylcarboxamido-adenosine (NECA) on plasma renin activity, atrial natriuretic peptide, cyclic guanosine 3, 5’-monophosphate (cGMP) and endothelin-1 in spontaneously hypertensive rats.MethodsThe drugs were administered intraperitoneally in four doses to conscious rats. Systolic blood pressure and heart rate were measured by the tail-cuff technique. Both humoral and hemodynamic parameters were determined 1 h after dosing in separate sets of animals.ResultsAll the compounds induced a dose-dependent decrease in systolic blood pressure that was associated with different changes in heart rate. Heart rate was decreased by all doses of CCPA and by the higher doses of the non-selective compound (NECA) and increased by both A2Aagonists. Plasma renin activity also changed in opposite directions, being decreased by CCPA but increased dose-dependently by 2HE-NECA and CGS 21680 and only moderately by NECA. Plasma atrial natriuretic peptide and cGMP levels increased dose-dependently after CCPA and NECA, but were unaffected by the A2Aagonists. None of the compounds altered plasma endothelin-1 levels.ConclusionsThese results indicate that the renin-suppressive effect of the A1agonist, which is associated with a cardiodepressant action, may be attributed either to a direct inhibition of renin release or to the concomitant increments in plasma atrial natriuretic peptide and its second messenger, cGMP. In contrast, the renin-stimulating effect of the A2Aagonists may result either from direct stimulation of renin secretion or from reflex sympathetic activation secondary to the fall in blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1996

数据来源: OVID