ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

In human subjects, the assessment of renal function and of its changes by interventions is limited to the measurement of glomerular filtration rate (GFR), renal blood flow and the estimation of proteinuria. In humans, GFR can be determined exactly by measuring the clearance of an ideal filtration marker, such as inulin. The classic method of measuring inulin clearance in humans includes constant intravenous infusion of the compound and timed collections of urine. In order to avoid the need for timed urine collections, a number of alternative procedures have been devised. All these methods only use determinations of inulin in plasma or serum. From these, the total body inulin clearance is obtained using pharmacokinetic calculations. In order to measure total body clearance, usually called plasma clearance, inulin is either given as a constant intravenous infusion or as a bolus infusion. Both procedures overestimate GFR because of incomplete distribution of inulin during the study periods. The error may be minimized by using model-independent pharmacokinetic calculations.Unlike inulin, creatinine is not a perfect filtration marker. This is because the substance is not only eliminated by glomerular filtration but also by tubular secretion. The extent of tubular creatinine secretion is not constant in various individuals. Serum creatinine concentration is a commonly used measure of renal function in clinical practice. This parameter is determined both by the renal elimination and by the production of the compound. Differences in creatinine production among subjects and over time in a single individual may occur because of changes in muscle mass.Radioisotopic filtration markers can easily and accurately be measured in plasma and serum. Using this method, the plasma concentration–time curve of these compounds can easily be studied after intravenous bolus injection. From the plasma concentration–time curves obtained, the total body clearance (plasma clearance) of the substances can be calculated using pharmacokinetic models. Most frequently,125I-iothalamate,99mTc-diethylenethiaminepenta-acetic acid and51Cr-ethylenediaminetetra-acetic acid are used for the estimation of GFR in humans. The total body clearance of all these filtration markers overestimates GFR. The error induced by this phenomenon is particularly relevant at low levels of GFR.In recent years, iohexol has been used as a filtration marker. The substance can be measured in plasma, serum and urine using high-performance liquid chromatography. So far, good agreement has been shown for GFR determined by the classic inulin clearance and by the iohexol plasma clearance.Screening for proteinuria is commonly performed using reagent test strips. Quantitative measurements of marker proteins can be used to estimate the extent and the site of damage in the nephron. These measurements may be used to estimate the progression of renal disease and the response to therapeutic interventions. Of particular interest is the degree of albuminuria which indicates nephropathy in diabetic patients and end-organ damage in patients with hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe role of arginine vasopressin (AVP) in the development and maintenance of arterial hypertension is controversial. Furthermore, it remains unclear whether chronic treatment with antihypertensive agents modulates levels of AVP, with potential secondary effects on vascular tone and fluid homeostasis.ObjectiveTo investigate the relation between plasma AVP and arterial blood pressure in a population-based sample of 534 middle-aged subjects.ResultsOverall, levels of AVP were higher in hypertensive subjects (2.15 ± 0.26 pg/ml; n = 289) than in normotensive subjects (1.45 ± 0.15 pg/ml; n = 245;P< 0.05). (Hypertension was defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg, or receiving antihypertensive medication.) In untreated individuals, plasma levels of AVP were found to be correlated with both systolic (r= 0.15,P= 0.002) and diastolic (r= 0.14,P= 0.005) blood pressure. The differences between the lowest and highest quartile of AVP levels were 5.1 mmHg (P= 0.03) and 2.6 mmHg (NS) for systolic and diastolic blood pressure, respectively, after adjustment for age and sex. Moreover, it appeared that the relation between AVP and blood pressure was particularly strong in subjects with low levels of renin (< 10 mU/l; n = 118; systolic blood pressurer= 0.24,P= 0.007; diastolic blood pressurer= 0.19,P= 0.03). Specifically, patients receiving monotherapy with diuretics (n = 39) or beta-blockers (n = 54) displayed elevated plasma levels of AVP (2.93 ± 0.98 pg/ml and 2.74 ± 0.74 pg/ml, respectively); however, only in patients taking diuretics was this finding apparently independent of confounding variables. Other monotherapies with angiotensin-converting enzyme inhibitors (n = 9) or Ca2+-antagonists (n = 19) were not associated with levels of AVP.ConclusionThe data suggest that plasma levels of AVP display a discernible relationship with arterial blood pressure and hypertension, particularly when renin levels are low. In addition, with the exception of diuretics, no modulation of AVP levels is attributable to the intake of antihypertensive agents as it occurs in a population-based sample.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundMany studies have shown that low birth weight is associated with high blood pressure. The composition of the diet of pregnant women has also been found to affect blood pressure in their children. We assessed the effect of prenatal exposure to the Dutch famine of 1944–1945, during which the caloric intake from protein, fat and carbohydrate was proportionally reduced, on blood pressures in adults now aged about 50 years.Methods and resultsWe measured blood pressures at home and in the clinic among people born at term in one hospital in Amsterdam, The Netherlands, between November 1 1943 and February 28 1947, for whom we had detailed birth records. Blood pressures of people exposed to famine during late (n= 120), mid-(n= 109) or early gestation (n= 68) were compared with those of people born in the year before or conceived in the year after the famine (unexposed subjects,n= 442). No effect of prenatal exposure on systolic and diastolic blood pressure was observed. The mean systolic blood pressure taken in the clinic in those exposed in late gestation, and adjusted for sex and age, was 1.3 mmHg higher than in the unexposed group (95% confidence interval −1.9 to 4.4). The mean systolic blood pressure differed by −0.6 mmHg (95% confidence interval −3.9 to 2.7) for those exposed in mid-gestation and −1.7 mmHg (95% confidence interval −5.6 to 2.2) for those exposed in early gestation. People who were small at birth had higher blood pressures. A 1 kg increase in birth weight was associated with a decrease of 2.7 mmHg (95% confidence interval 0.3 to 5.1) in systolic blood pressure. Analyses of blood pressures measured at home gave similar results.ConclusionHigh blood pressure was not linked to prenatal exposure to a balanced reduction of macronutrients in the maternal diet. However, it was linked to reduced fetal growth. We postulate that it might be the composition rather than the quantity of a pregnant woman's diet that affects her child's blood pressure in later life.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate whether the clinic–daytime blood pressure difference can provide information on vascular reactivity to stress comparable to that of simple noninvasive stimuli such as a cold pressor test and isometric exercise, and whether there is any relationship between this blood pressure difference and noninvasive measurements of the left ventricular mass and carotid arterial wall.DesignPatients with newly discovered, never-treated, sustained hypertension were included in the study after a 1 month run-in, during which time their blood pressure was measured three times at 2 week intervals.MethodsBlood pressure was measured by a noninvasive procedure at rest and during a cold pressor test and an isometric exercise. The difference was calculated for systolic, diastolic and mean blood pressure as resting minus daytime ambulatory blood pressure. Parameters of the posterior wall and septal thickness of the left ventricle, aortic root and left atrium were studied by M-mode echocardiography. Carotid wall thickness and diameter were measured using ultrasound.ResultsThe 90 patients enrolled in the study were divided into tertiles of clinic–daytime blood pressure difference. The composition of the groups differed in sex, since the majority of women were in the highest tertile, but was comparable for age, body mass index, renin-aldosterone axis and lipid and carbohydrate metabolism. Blood pressure responses to cold and isometric exercise were more pronounced in patients in the lowest tertile of blood pressure difference. No intergroup differences were detected in echocardiographic parameters of ventricular (left ventricular mass, tertiles I–III: 46.5 ± 10, 42.3 ± 8,44.8 ± 13 g/m 2:7, respectively) and carotid (intima–media thickness, tertiles I–III 0.58 ± 0.1, 0.54 ± 0.1,0.62 ± 0.1 mm, respectively) structure.ConclusionsThe present study indicates that the clinic–daytime blood pressure difference provides different information on cardiovascular reactivity compared with that obtained from the cold pressor test and isometric exercise. Moreover, it does not seem to have any relationship with ventricular hypertrophy and/or carotid wall thickening.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate whether genetic variations in the genes encoding the α and β subunits of the Na,K-ATPase are linked with hemodynamic phenotypes.Design and participantsCross-sectional data based on 533 subjects (no antihypertensive medication) were obtained from 150 families of phase 2 of the Quebec Family Study, together with longitudinal data from 338 subjects (105 families) who had been measured 12 years earlier in phase 1 of the Quebec Family Study.Main outcome measuresRestriction fragment length polymorphisms were examined at the α2(exon 1 and exon 21–22 withBglII) and β1(MspI andPvuII) loci of Na,K-ATPase. Hemodynamic phenotypes measured included systolic and diastolic blood pressure, heart rate and rate–pressure product at rest and during low-intensity exercise.ResultsSib-pair analysis revealed relatively strong linkages (P= 0.0003–0.002) between the resting heart rate and rate–pressure product and the α2exon 21–22 marker and α2haplotype. Moreover, the α2exon 21–22 marker showed suggestive linkages (P= 0.01 to 0.043) with resting systolic blood pressure and exercise diastolic blood pressure, heart rate and rate–pressure product, and the α2haplotype with exercise diastolic blood pressure and rate–pressure product and the 12-year change in resting systolic blood pressure (P= 0.03 to 0.05). Both the β1MspI marker and the β1haplotype were linked with the resting rate–pressure product (P = 0.007 and 0.003, respectively), and all β1markers showed linkage with the change in resting systolic blood pressure (P= 0.00005 to 0.024). In men, there was a significant (P= 0.01) interaction between the α2exon 21–22 genotype and the postglucose plasma insulin level with regard to resting systolic blood pressure.ConclusionsThese data suggest that the α2and β1genes of Na,K-ATPase contribute to the regulation of hemodynamic phenotypes in healthy subjects.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveIt has been reported that the deletion allele of the insertion/deletion polymorphism of the angiotensin I converting enzyme gene is associated with increased cardiovascular risk and progressive renal disease, including immunoglobulin A nephropathy. We therefore investigated the relationship between angiotensin converting enzyme polymorphism and intrarenal microvascular structure in 56 patients with nondiabetic renal disease.Methods and resultsWe determined various cardiovascular hormones of the renin–angiotensin system and angiotensin converting enzyme gene polymorphism in 56 patients with nondiabetic renal diseases who underwent a renal biopsy. The patients were divided into three groups by angiotensin converting enzyme genotype (insertion/insertion,n= 21; insertion/deletion,n= 23; deletion/deletion,n= 12) using polymerase chain reaction methods. The angiotensin converting enzyme insertion/ deletion and deletion/deletion genotypes were associated with a significantly higher interlobular artery wall: lumen ratio than the insertion/insertion genotype (insertion/ insertion 0.27 ± 0.01, insertion/deletion 0.32 ± 0.01, deletion/deletion 0.33 ± 0.02;P< 0.05). Afferent arteriolar and tubulo-interstitial injury scores were similar among the three genotypes. Although serum angiotensin converting enzyme activity was higher in the deletion/deletion than in the other two genotypes (insertion/insertion 9.7 ± 0.7, insertion/deletion 10.7 ± 0.9, deletion/deletion 14.0 ± 2.4 IU/l;P< 0.05), other factors of the renin–angiotensin system, including blood pressure and serum creatinine levels, were not different among the three groups.ConclusionsThe angiotensin converting enzyme deletion/deletion genotype may be considered a risk factor for the development of microvascular wall thickening in nondiabetic renal diseases.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe use of cyclosporine A after organ transplantation is associated with a high incidence of hypertension, but the underlying mechanisms for this process are not clear. We investigated the effects of blockade of basal release of endothelial nitric oxide and the effects of endothelium-independent and -dependent vasodilators and vasoconstrictors in patients treated with cyclosporine A after heart transplantation.DesignWe measured blood pressure and forearm blood flow responses to brachial artery infusions of NG-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, acetylcholine, norepinephrine and vasodilating and vasoconstricting doses of endothelin-1 in eight patients early (< 3 months) and in 11 patients late (> 18 months) after transplantation.ResultsDiastolic blood pressure was higher late after transplantation, but calculated forearm vascular resistance was lower (P< 0.01). Thus, increased forearm vascular resistance does not contribute to the increase in blood pressure. The vasoconstrictor response to L-NMMA was similar in both groups but a reduced endothelium-dependent vasodilator response to acetylcholine was seen late after transplantation. However, impaired smooth muscle responsiveness to nitric oxide may have contributed to this finding, since the response to sodium nitroprusside tended to be reduced. Vasoconstrictor responses to norepinephrine and endothelin-1 were comparable but no vasodilation was seen with low doses of endothelin-1 late compared with early after transplantation (P< 0.05).ConclusionsThe findings in the forearm circulation question the concept of generalized increases in vasoconstrictor responses or a disturbance of tonic, basal release nitric oxide in the pathogenesis of cyclosporine-A-induced hypertension. Although the forearm vasodilator responses to the stimulation of endothelial nitric oxide production and release by acetylcholine, and to low doses of endothelin-1, were impaired, these findings could be explained by the increase in blood pressure rather than cyclosporine A itself.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo characterize and compare mechanosensitive cell currents in rat aortic endothelial cells from spontaneously hypertensive and Wistar–Kyoto rats.Methods and resultsBy use of the patch-clamp technique, we investigated whole-cell currents of native rat aortic endothelial cells in the presence of mechanical stimulation elicited by hyposmotic cell swelling. In rat aortic endothelial cells, this hypotonic cell swelling induced a fourfold increase in outward-directed whole-cell currents carried by K+, leading to cell hyperpolarization and a small increase in inward-directed currents. Gadolinium, a blocker of stretch-activated cation channels, completely blocked hypotonic cell swelling-induced outward-and inward-directed whole-cell currents. Charybdotoxin, a blocker of Ca2+-dependent K+channels, decreased hypotonic cell swelling-induced outward-directed currents by up to 85%. Disruption of actin filaments by cytochalasin B and of microtubuli by nocodazole reduced the activation of hypotonic cell swelling-induced whole-cell currents by 91 and 71%, respectively. In experimental hypertension, hypotonic cell swelling-induced whole-cell conductance was significantly increased in spontaneously hypertensive rats (331 ± 20 pS/pF) compared with normotensive controls (167 ± 7 pS/pF,P< 0.01), whereas basal and agonist-induced cell conductances were not altered.ConclusionsIncreased hypotonic swelling-induced currents in aortic endothelial cells from spontaneously hypertensive rats presumably reflect an increased density or mechanosensitivity of stretch-activated ion channels in experimental hypertension. The increased mechanosensitive whole-cell currents might indicate an altered endothelial mechanotransduction in experimental hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe prepro-adrenomedullin gene encodes the biologically active peptide adrenomedullin, which acts as a potent vasodilator as well as a modulator of vascular smooth muscle cell growth. We investigated the question of whether adrenomedullin is regulated in response to metabolic perturbations in vascular smooth muscle.Materials and methodsAcute inhibition of glycolysis, leading to partial depletion of cellular ATP, was produced in cultured rat aortic vascular smooth muscle cells by replacing glucose with 2-deoxyglucose. Solution hybridization/RNase protection analysis was used to quantitate changes in expression of the prepro-adrenomedullin messenger RNA and a specific radioimmunoassay was used to assess levels of secreted adrenomedullin.ResultsAcute incubation of rat aortic vascular smooth muscle cells with 2-deoxyglucose caused a rapid and sustained induction of low basal levels of adrenomedullin messenger RNA, which reached twice the control levels by 1 h and four times control levels by 6 h. The induction of adrenomedullin messenger RNA expression was dependent upon de-novo gene transcription and was reversed by the re-introduction of glucose. Despite the sustained increase in adrenomedullin messenger RNA, secretion of immunoreactive-adrenomedullin from vascular smooth muscle cells was reduced by as much as 75% and paralleled the inhibition of radiolabeled aminoacid incorporation into protein during glycolytic inhibition; both parameters recovered towards control levels following re-introduction of glucose.ConclusionsThe rapid and reversible activation of the adrenomedullin gene and inhibition of adrenomedullin peptide release in response to metabolic inhibition suggest that adrenomedullin represents a novel localized mechanism that may modulate regional blood flow and vascular smooth muscle cell proliferation in response to perturbations of normal metabolism.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID