摘要:

Ischemic renal disease (IRD) is defined as a clinically important reduction in glomerular filtration rate or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents itself in the setting of extrarenal arteriosclerotic vascular disease in older individuals with azotemia. Eleven to 14% of end-stage renal disease (ESRD) cases are attributable to chronic IRD. A high percentage of patients entering ESRD programs are hypertensive. Many patients with a presumed diagnosis of hypertensive nephrosclerosis actually have undiagnosed ischemic nephropathy as the etiology of their ESRD. It is important for the clinician to identify IRD, because IRD is a potentially reversible cause of chronic renal failure in a hypertensive patient.Atherosclerotic renal artery disease is common among patients with coronary artery disease and aortic and peripheral vascular disease. Atherosclerotic renal artery disease is a progressive disorder, and its progression is associated with loss of renal mass and functioning.A decrease in glomerular filtration rate sufficient to cause an elevation of the serum creatinine concentration requires injury to both kidneys. Consequently, IRD can arise from one of two main clinical situations: bilateral hemodynamically significant renal artery stenosis leading to bilateral renal ischemia; and hemodynamically significant renal artery stenosis in a solitary functioning kidney, or in a kidney that is providing the majority of a patient's glomerular filtration.The primary reason for establishing the diagnosis of IRD is the hope that correction of a renal artery stenosis will lead to improvement of renal function, or a delay in progression to ESRD. There are six major clinical settings in which the clinician could suspect IRD: acute renal failure caused by the treatment of hypertension, especially with angiotensin converting enzyme inhibitors; progressive azotemia in a patient with known renovascular hypertension; acute pulmonary edema superimposed upon poorly controlled hypertension and renal failure; progressive azotemia in an elderly patient with refractory or severe hypertension; progressive azotemia in an elderly patient with evidence of atherosclerotic disease; and unexplained progressive azotemia in an elderly patient.Noninvasive testing modalities that have been used recently include the angiotensin converting enzyme inhibitor renal scan, duplex Doppler sonography, magnetic resonance angiography, and the spiral computed tomography. Treatment methods include percutaneous transluminal angioplasty, endovascular stenting, and surgical revascularization. The results of treatment for preservation of renal function have been encouraging, with stabilization or improvement in renal function observed in a significant proportion of cases.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo identify possible causes of inaccuracy in the use of the Hawksley random-zero sphygmomanometer and methods that could reduce this.MethodsFour Hawksley random-zero sphygmomanometers were compared with a standard sphygmomanometer under static conditions. Two methods (standard and rapid) were used to release pressure from the inflated cuff with pressures recorded by independent blinded observers. The rate at which the hand valve released pressure was analysed. The effects of varying filling times and pressures on the size of the final zero correction were investigated.ResultsThe Hawksley devices all under-recorded pressure compared with that measured by using a standard machine. A rapid means of pressure release approximately halved this error in each case. Pressure release through the hand valve was shown to have a characteristic and prolonged exponential decay. Using low filling times and pressures reduced the observed range of zeros seen, with the production of a correlation between the size of the zero and the inflation pressure used.ConclusionThese findings suggest that overestimation of the final zero correction is a common and major source of error in the use of the Hawksley sphygmomanometer. A simple change in the design of the final pressure release would improve the machine's reliability in clinical usage. The machine's zero mechanism is susceptible to unintentional misuse. Such misuse could occur when the machine is used in accordance with current sphygmomanometry guidelines.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundA mutation in the gene for the angiotensin II type 1 (AT1) receptor (A1166C) has been reported to be associated with primary hypertension.ObjectiveTo determine whether this observation could be confirmed with a different population sample.DesignWe examined 414 individuals with primary hypertension and 172 normotensive controls.MethodsThe mutation in the gene for the AT1receptor was detected using restriction polymerase chain reaction.ConclusionsWe detected no association of the AT1receptor polymorphism with hypertension, but a trend towards a decreased prevalence of the1166C allele among hypertensive patients with a late age at diagnosis (≥ 50 years) was observed.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo examine and compare angiotensin II type 1 receptor genotype and its relationship to platelet angiotensin II binding for pre-eclamptic and normotensive pregnant women.DesignIn a case‐control study, 43 pre-eclamptic women and 83 normotensive women were genotyped at the angiotensin II type 1 receptor gene locus. Platelet angiotensin II binding was measured for a subset of 11 pre-eclamptic and 57 normotensive pregnant women. We genotyped 162 healthy blood donors also, to examine the allelic background and patterns of linkage disequilibrium in the Nottingham population.MethodsPatients were recruited during pregnancy using a rigorous definition of pre-eclampsia. DNA was extracted from peripheral venous blood and genotyped at six previously described diallelic polymorphisms in the angiotensin II type 1 receptor gene, using competitive allele-specific oligonucleotide hybridization, and at a dinucleotide repeat polymorphism in the 3′ flanking region of the gene. Platelet angiotensin II binding and plasma angiotensin II concentrations were determined for peripheral venous blood.ResultsNormotensive pregnant women homozygous for cytosine at nucleotide 573 had significantly higher levels of platelet angiotensin II binding than did heterozygous women and women homozygous for thymidine at this site. Pre-eclamptic women had significantly higher levels of platelet angiotensin II binding than did normotensive pregnant women. The frequencies of allelic variants did not differ significantly between normotensive and pre-eclamptic women.ConclusionThe physiological regulation of platelet angiotensin II type 1 receptor expression in normal pregnancy is determined in part by angiotensin II type 1 receptor genotype. There was no evidence that the polymorphisms in the angiotensin II type 1 receptor gene were associated with pre-eclampsia.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundApparent mineralocorticoid excess (AME) is a cause of low-renin, low-aldosterone hypertension in which cortisol acts as a mineralocorticoid. The condition reflects an inability to inactivate cortisol to cortisone due to defective activity of the type 2 isozyme of 11b-hydroxysteroid dehydrogenase (11β-HSD2). Homozygous mutations in 11b-HSD2 gene in patients with AME have been described. A 7-year-old Brazilian girl had previously been found to have AME. Her father recently presented with mineralocorticoid hypertension at age 38 years.ObjectiveTo describe the clinical details, to perform steroid analyses and to assess the molecular basis for the hypertension in this kindred.MethodsThe 11βHSD2 gene was amplified from genomic DNA by the polymerase chain reaction and sequenced by direct chain-termination sequencing on an automatic DNA sequencer. The sequencing results were validated by restriction-site polymorphism. The mutant 11β-HSD2 protein was expressed in Chinese hamster ovary polyoma cells and enzymatic activity was assessed by metabolizing cortisolin vitro.ResultsSequence analysis of genomic DNA revealed a novel C1061T point mutation in exon V of the human 11β-HSD2 gene, resulting in an amino acid substitution of alanine by valine at codon 328 of the enzyme protein (A328V). Expression studies confirmed that the mutant protein was devoid of 11β-HSD2 activity. AHhaI restriction-site polymorphism confirmed that the proband was homozygous for the mutation whereas both parents were heterozygotes. The father of the proband had hypertension, a normal serum potassium level, suppressed plasma renin activity and plasma aldosterone level and a moderately elevated urinary cortisol: cortisone metabolite ratio.ConclusionsAME in this kindred is caused by a novel mutation in the 11β-HSD2 gene. Detection of hypokalaemia, at least in this kindred, is an insensitive screening test for mineralocorticoid-based hypertension. In contrast to results from previously investigated kindreds, we have demonstrated that this kindred has an abnormal phenotype in the heterozygote state. Further studies are now required in order to evaluate the role of 11β-HSD2 activity in the pathophysiology of ‘essential’ hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine whether sex influences the rate of sodium–proton (Na+-H+)-exchange-dependent swelling of platelets from patients with essential hypertension and normotensive controls.MethodPlatelet swelling was detected by measuring the change in optical density of platelet suspensions added to sodium propionate buffer, pH 6.7, at 37°C. We studied 56 subjects, 28 men and 28 women, each group containing 14 normotensive and 14 hypertensive subjects. The groups were well matched for sex, ethnicity and age.ResultsThat platelet swelling was dependent on Na+-H+exchange was demonstrated by performing blockade by 5-(N,N-hexamethylene)-amiloride and by measuring its dependence on extracellular Na+concentration. The rate of swelling of platelets from hypertensive men [(14.2 ± 0.9) × 10−3/s] was higher than that of those from normotensive men [(10.1 ± 0.5) × 10−3/s], normotensive women [(10.0 ± 0.5) × 10−3/s] and hypertensive [(11.1 ± 0.8) × 10−3/s] women. The interaction between sex and hypertension was significant (P< 0.05 by analysis of variance).ConclusionsSex influences the effect of hypertension on the rate of swelling of platelets exposed to sodium propionate (pH 6.7).

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundThe nature of the cellular abnormality causing hypokalemia, hypotension, and hypovolemia in Bartter's and Gitelman's syndromes is still being debated. In fact, despite the recent descriptions of an array of nonconservative missense or point mutations in some ion transporters and in K+channel, the lack of detectable defects in some patients suggests that other abnormalities of cell ion homeostasis may be involved in the pathophysiology of these syndromes. The study of the activity of cell ion transporters in patients with these syndromes using red blood cells (RBC) as a cellular model never investigated the role of plasma factor(s) affecting ion transport.ObjectiveTo evaluate the effect of plasma from patients with these syndromes on furosemide-sensitive lithium efflux (FSLE) from lithium (Li+)-loaded RBC of healthy subjectsin vitro.MethodsRBC of healthy controls were loaded with Li+in the presence of nystatin and FSLE was evaluated in the presence of various concentrations of plasma from controls and patients with the two syndromes.ResultsPlasma from controls did not affect FSLE (0.08 ± 0.02 mmol/l cells per h with 1: 4 vol: vol and 0.07 ± 0.02 mmol/l cells per h with 1: 2 vol: vol plasma dilution). In contrast, doubling concentrations of plasma from patients with either syndrome in the efflux solution halved FSLE (from 0.10 ± 0.0 mmol/l cells per h with 1: 4 vol: vol to 0.05 ± 0.01 mmol/l cells per h with 1: 2 vol: vol plasma dilution,P< 0.05). Na+/Li+exchange was significantly greater for RBC from patients with either syndrome than it was for RBC from controls (0.373 ± 0.06 versus 0.257 ± 0.01 mmol/l cells per h,P< 0.01), but the kinetic properties of furosemide-sensitive Na+-K+-2Cl−cotransport were similar.ConclusionThese data provide evidence for the hypothesis that plasma factor(s) affect ion transport in patients with these two syndromes. Since FSLE estimates Na+-K+-2Cl−cotransport the data suggest that plasma factor(s) contribute(s) to K+wasting, hypokalemia, and hypotension by inhibiting cotransport in patients with these syndromes. The increase of Na+/Li+exchange is most likely a secondary phenomenon associated with the hypermineralocorticoid state.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundWe had previously demonstrated that the distensibility of the carotid artery in spontaneously hypertensive rats (SHR) aged 18 weeks does not differ from that of the carotid artery in normotensive animals for common pressure levels, despite vascular hypertrophy in SHR.ObjectiveTo examine the time-course effects of hypertension on the geometry and the mechanical properties of the carotid artery in SHR.MethodsThe mechanical behavior of the carotid arteries of anesthetized SHR, stroke-prone SHR (SHRSP), and Wistar–Kyoto (WKY) rats aged 4, 8, 12, 16, and 32 weeks was examined by simultaneously measuring the internal diameter with an A-mode ultrasonic echotracking device and the intra-arterial pressure with a computerized data-acquisition system. Histometric measurements of the carotid artery were performed after death of rats.ResultsBlood pressure increased with time in rats of the two genetic hypertensive models. However, it rose earlier and to higher levels in the SHRSP. Cardiac hypertrophy was comparable in the two hypertensive groups whereas vascular hypertrophy was less pronounced in the SHRSP than it was in the SHR. There was an age-related decrease in arterial distensibility in rats of all groups that was more pronounced in the SHRSP than it was in the SHR compared with that in WKY rats (decreases of 57 and 36%, respectively, versus WKY rats aged 32 weeks;P< 0.05).For rats of all ages studied, although aging affected differently the vascular properties of the distinct animal strains, arterial distensibility was increased in the SHR and SHRSP compared with that in control animals for similar blood pressure levels, implying a rightward shift of the distensibility–pressure curves in the two hypertensive models. However, there was a significant reduction in arterial distensibility in rats of the two hypertensive strains at their respective mean blood pressues, compared with that in control animals.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundThe dynamic elastic modulus of central arteries is very frequency-dependent. Although resting heart rate is a potent independent risk factor for morbidity and mortality both from cardiovascular and from noncardiovascular disease, no link between tachycardia and arterial stiffness has ever been established.ObjectiveTo relate arterial stiffness to heart rate in a population with relatively low cardiovascular risk.MethodsPulse-wave velocity measurements and highresolution echo-tracking techniques were used to determine the degree of arterial distension (of carotid and femoral arteries, and terminal aorta) and the velocity of the pulse wave (aorta and upper and lower limbs) at the same time as heart rate, in members of a large population of normotensive and hypertensive subjects in a multicenter study in Paris, Fleury-Merogis and Grenoble (France).ResultsA high heart rate was strongly associated with reduced distension and elevated pulse-wave velocity, even after adjustment for age and blood pressure. A high aortic pulse-wave velocity was also negatively associated with a low baroreflex sensitivity. The most significant associations between high heart rate and high arterial rigidity were found for the carotid artery, the thoracic aorta, and the lower limbs, but there was no significant result for the terminal aorta and the arm arteries.ConclusionThis study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate post-receptor mechanisms that underlie enhanced angiotensin II (Ang II)-stimulated cytosolic free Ca2+concentration ([Ca2+]i) responses in vascular smooth muscle cells from small arteries of SHR.MethodsTo determine whether Ca2+influx is altered in SHR, effects of Ca2+channel antagonists (nitrendipine and diltiazem) and depletion of extracellular Ca2+on Ang II-stimulated [Ca2+]iresponses in primary cultured unpassaged vascular smooth muscle cells from mesenteric arteries of spontaneously hypertensive rats (SHR), Wistar and Wistar-Kyoto (WKY) rats aged 17 weeks were studied. To assess whether Ca2+stores contribute to increases in Ang II-stimulated Ca2+mobilization and [Ca2+]iin SHR, cells were exposed to thapsigargin, a selective reticular Ca2+-ATPase inhibitor. [Ca2+]iwas measured by fura-2 methodology.ResultsBasal and 1 nmol/l Ang II-stimulated [Ca2+]iwere significantly greater in SHR cells (123 ± 7.1 nmol/l basal; 268 ± 7.0 nmol/l stimulated) than they were in those from WKY rats (88 ± 4.8 nmol/l basal; 221 ± 8.6 nmol/l stimulated) and Wistar rats (85 ± 3.0 nmol/l basal; 216 ± 8.3 nmol/l stimulated). In Ca2+-free medium, basal and Ang II-induced [Ca2+]iwere reduced in all groups, but Ang II-stimulated [Ca2+]iresponses were still significantly enhanced in SHR cells compared with those in Wistar and WKY rat cells (205 ± 11.2 versus 173 ± 8.0 and 161 ± 2.6 nmol/l, respectively). Administrations of 10−6mol/l diltiazem and 10−7mol/l nitrendipine decreased Ang II-elicited [Ca2+]iresponses and normalized basal [Ca2+]iin SHR cells. The inhibition induced by Ca2+channel antagonists was greater (P<0.05) in WKY and Wistar rat cells than it was in those from SHR. Administration of thapsigargin, in Ca2+-free buffer, induced a greater (P<0.05) dose-dependent [Ca2+]iincrease in SHR cells than it did in WKY rat cells. Administration of 1 nmol/l Ang II increased [Ca2+]iin thapsigargin-pretreated cells of SHR but not in those of WKY rats.ConclusionDifferent mechanisms contribute to increases in basal and Ang II-stimulated [Ca2+]iresponses in vascular smooth muscle cells from small arteries of SHR, which contribute to elevated peripheral resistance in hypertension. Increases in basal [Ca2+]imay be partly due to augmentation of Ca2+influx, whereas Ang II-induced [Ca2+]ihyper-responsiveness might depend primarily on Ca2+mobilization rather than on influx of extracellular Ca2+.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID