摘要:

BackgroundEffective antihypertensive treatment has prevented target-organ involvement in hypertension, markedly reducing morbidity and mortality from strokes, coronary heart disease, cardiac failure, and hypertensive emergencies. However, the incidence of hypertension-related end-stage renal disease continues to increase, suggesting that therapeutic reduction in arterial pressure by itself is not sufficient to prevent the development of hypertensive renal failure.ObjectiveTo examine experimental and clinical data concerning the protective effect of reduction of arterial pressure on the progression of hypertension-related renal disease, and the evidence indicating that some antihypertensive agents may afford more nephro-protection, over and above that attributable to reduction of arterial pressure.ResultsResults of numerous studies clearly indicate that adequate control of arterial pressure, irrespective of the antihypertensive agent used, slowed the progression of renal disease. Results of some studies suggest that lowering arterial pressure below the level that is usually considered adequate has an additional beneficial effect by slowing the progression of renal injury.ConclusionResults of a number of studies evaluating nephroprotective effects of various drugs and regimens have indicated that certain agents, most notably angiotensin converting enzyme inhibitors and their combination with calcium antagonists, afford more protection than do others at similar levels of reduction of arterial pressure. Results of still other studies suggest that certain agents that exert greater nephroprotection are more efficient at controlling arterial pressure. Therefore, further data are needed before any final conclusion can be drawn. However, it is clear that, in order to establish nephroprotection in patients with essential hypertension, the problem should not be further complicated by additional comorbid diseases such as diabetes mellitus.J Hypertens16:555–567 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe relationship between circulating levels of angiotensinogen and hypertension in the epidemio-logic setting has not been studied much. Recent findings related to the association between hypertension and polymorphisms of the angiotensinogen gene have generated new interest in this potential pathway to hypertension.ObjectivesTo examine environmental factors associated with levels of circulating angiotensinogen as determinants of hypertension in populations of African origin.MethodsWe recruited 1557 participants from communities in Nigeria (n = 611), Zimbabwe (n = 161), Jamaica (n = 476), and Maywood, Illinois, USA (n = 309).ResultsMean angiotensinogen levels varied widely across groups (Nigeria 1381 ng/ml angiotensin I generated, Zimbabwe 1638 ng/ml angiotensin I generated, Jamaica 1808 ng/ml angiotensin I generated, and Maywood 2039 ng/ml angiotensin I generated). Average body mass index was highly correlated to angiotensinogen level across the population samples, accounting for 90% of the between-sample variation. At the individual level the correlation between body mass index and angiotensinogen level was substantially smaller, in the range 0.04–0.15, although the association attained statistical significance for all but one of the populations. Women had higher levels of angiotensinogen and mean levels in subjects of both sexes declined in late middle age. Hypertensives also had significantly higher levels of angiotensinogen and we noted correlations to blood pressure for two of the four populations.ConclusionObesity, sex and age would all appear to be important modifiers of circulating angiotensinogen levels. The variation in level across populations was substantially larger than that which has been found previously in association with known genetic polymorphisms within populations, suggesting the possibility that environmental effects are more important than had previously been recognized.J Hypertens16:571–575 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo determine the risk of death from coronary heart disease, stroke, all cardiovascular disease and all-cause mortality associated with systolic blood pressure and in particular with isolated systolic hypertension among the middle-aged population.Methods and designA prospective 15-year cohort study of two independent cross-sectional random samples of subjects participating in baseline surveys in 1972 and 1977. Each survey included a self-administered questionnaire, measurements of height, weight and blood pressure and the determination of the serum cholesterol concentration.SettingNorth Karelia and Kuopio provinces in eastern Finland. Mortality follow-up complete with the personal identification number.ParticipantsParticipants were 10 333 men and 11 160 women aged 25–64 years without histories of myocardial infarction and stroke incidence at the time of the baseline survey. Isolated systolic hypertension in these analyses was defined as systolic blood pressure ≥ 160 mmHg and diastolic blood pressure < 95 mmHg. Subjects with blood pressure < 160/90 mmHg were considered normotensive.ResultsCoronary heart disease, stroke, cardiovascular disease and all-cause mortality among men and women aged 45–64 years increased with the increasing systolic blood pressure. Among women aged 45–64 years, isolated systolic hypertension increased the relative risk of these fatal events. Among men aged 45–64 years, only coronary heart disease mortality was significantly associated with isolated systolic hypertension.ConclusionIsolated systolic hypertension is an important predictor of death from coronary heart disease, stroke, cardiovascular disease and all causes for women. For men aged 45–64 years, the risk of death from coronary heart disease was associated with isolated systolic hypertension, but the risk of stroke, cardiovascular disease and all-cause mortality associated with increasing systolic blood pressure was evident already at the systolic blood pressure levels < 160 mmHg, independently of the level of diastolic blood pressure.J Hypertens16:577–583 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundWe recently demonstrated that arachidonic: linoleic acid ratio of erythrocytes of essential hypertension patients is greater than normal.ObjectiveTo investigate fatty acid composition, capability for adhesion to biological substrate and expression of β2integrins of leucocytes obtained from peripheral blood and skin window exudate of essential hypertension patients.DesignNeutrophil activation state was evaluated by reproducing the various conditions occurringin vivoduring the life of the cell (i.e. under the ‘resting’ condition, such as in peripheral blood, and ‘primed’ condition, such as after transmigration through the endothelium and after administration of specific chemo-attractants). Because both peripheral blood and skin window leucocytes of the subjects were obtained on the same day, we could be sure that there had been no dietary influences on changes in levels of fatty acid. Thus, the observed changes should reliably reflect the metabolic rate of utilization of fatty acids coupled to the activation and migration of cells.ResultsLeucocytes from essential hypertension patients were richer in arachidonic acid than were the corresponding cells from normotensive subjects; this difference was also evident for functionally activated skin window leucocytes, in spite of there having been a greater loss of poly-unsaturated fatty acids and arachidonic acid after migration. Moreover, a greater than normal arachidonic acid : linoleic acid ratio was shown for the first time to apply for leucocytes of essential hypertension patients, so extending our previous findings on the erythrocytes. Leucocytes from essential hypertension patients, collected both from peripheral blood and from skin window exudate, proved far more adhesive than the corresponding cells from age-matched and sex-matched controls, but this was not associated with a quantitative hyperexpression of β2integrins.ConclusionsThe results suggest that an increase in availability of arachidonic acid in leucocytes could be a further expression of the generalized disturbance of fatty acid levels associated with essential hypertension and that a condition of hyperadhesion of neutrophils could occur spontaneouslyin vivoduring the course of hypertension.J Hypertens16:585–592 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo determine adrenocorticotrophin dose–response relationships for increase of blood pressure and metabolic parameters of the Sprague–Dawley rat.MethodsWe injected 120 male Sprague–Dawley rats twice daily subcutaneously for 10 days with 0.5, 1, 5, 50, 100, 200 or 500 μg/kg synthetic adrenocorticotrophin per day (all n = 10) or subjected them to sham injection (0.9% NaCl; n = 50). Systolic blood pressure, 24 h food intake, water intake, urine volume and body weight were measured. Data from a further 45 rats treated with 500 μg/kg per day adrenocorticotrophin in previous studies were included in the blood pressure analyses. After we had killed these rats, their organ weights (kidney, heart, adrenal) and plasma electrolyte, adrenocorticotrophin and serum corticosterone concentrations were measured.ResultsOn the final day of treatment systolic blood pressure of sham-injection control rats was 123 ± 1 mmHg (n = 50). Compared with sham treatment, a low dose of adrenocorticotrophin (1 μg/kg per day) increased systolic blood pressure from 122 ± 1 to 130 ± 2 mmHg (P< 0.001) without any metabolic effects, whereas a high dose of adrenocorticotrophin (500 μg/kg per day) increased systolic blood pressure from 121 ± 1 to 150 ± 2 mmHg (P< 0.001, n = 55) with increases in intake of water and urine volume (P< 0.001, n = 10) and a decrease in body weight (P< 0.001, n = 10). Plasma adrenocorticotrophin and serum corticosterone concentrations for the sham-injection control group were 162 ± 12 pg/ml (36 ± 3 pmol/l) and 376 ± 18 ng/ml (1038 ± 50 nmol/l), respectively. Plasma adrenocorticotrophin concentration was elevated by injections of 100 (P< 0.05), 200 (P< 0.01) and 500 μg/kg adrenocorticotrophin per day (P= 0.001). Serum corticosterone concentration was not significantly different from that of sham-injection rats with 0.5–5 μg/kg adrenocorticotrophin per day but was increased by injection of 50–500 μg/kg adrenocorticotrophin per day (P< 0.001).ConclusionsThese results define 1 μg/kg adrenocorticotrophin per day, administered subcutaneously, as the threshold dose for causing a rise in blood pressure in the rat. Thus administration of adrenocorticotrophin increases systolic blood pressure at doses that induce minimal adrenocorticotrophin metabolic effects. Administration of a low dose of adrenocorticotrophin to the rat is a suitable model for stress-induced hypertension.J Hypertens16:593–600 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundDysfunctional dopamine neurotransmission and greater than normal retention of salt have been found for renal proximal tubules of the spontaneously hypertensive rat.ObjectiveTo determine whether there are differences between kidney D1Adopamine receptor distributions of spontaneously hypertensive rats and Wistar–Kyoto rats.MethodsWe examined the expression of D1Adopamine receptors in kidneys of spontaneously hypertensive rats and the normotensive Wistar–Kyoto rat through Western blots and immunocytochemistry, using highly specific antipeptide antibodies directed against the receptor.ResultsThe specificity of the antisera was demonstrated by Western blot studies, using proximal tubules, from Wistar–Kyoto rats. The antiserum recognized a major polypeptide withMrof 72 kDa and a minor protein ofMr66 kDa, which were not detected either by antigen-adsorbed or by preimmune sera. In renal cortex of both Wistar–Kyoto rats and spontaneously hypertensive rats, D1Areceptors were expressed at equivalent levels. In the inner medulla of Wistar–Kyoto rat, there was diminished (by 60%) expression of D1Areceptors compared with that of the renal cortex. However, the expression of D1Areceptors in the inner medulla in the spontaneously hypertensive rat was even more diminished (by 83%) relative to levels found in spontaneously hypertensive rat renal cortex. Immunocytochemical studies localized the D1Areceptor protein in renal cortex primarily to epithelia of tubules. Relative to renal cortex, there was an overall decrease in staining intensity in the inner medulla both of Wistar–Kyoto rats and of spontaneously hypertensive rats. Compared with that of Wistar–Kyoto rat, the intensity of staining of D1Areceptors in the inner medulla of spontaneously hypertensive rats was greatly diminished, confirming the Western blot analyses. The less than normal expression of D1Areceptors in the inner medulla of spontaneously hypertensive rats might be of physiologic importance in the etiology of greater than normal retention of salt and hypertension in spontaneously hypertensive rats.J Hypertens16:601–608 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesTo examine the role of nitric oxide in the cardiovascular system in spontaneous hypertension. In particular, we wanted to know whether the production of nitric oxide in the cardiovascular system of the spontaneously hypertensive rat is different from that of the normotensive Wistar–Kyoto rat and whether nitric oxide is biologically effective in this system.DesignWe studied various aspects of the L-arginine–nitric oxide pathway in the cardiovascular system of spontaneously hypertensive rats and Wistar–Kyoto rats.MethodsTo address the first objective we analysed the expression of endothelial nitric oxide synthase in the heart by Western blotting and the activity of constitutive nitric oxide synthase in resistance microvessels obtained from the mesenterium, both from spontaneously hypertensive rats and Wistar–Kyoto rats aged 14–18 weeks. We also analysed the concentration of the oxidative product of nitric oxide, nitrate, in plasma from these rats. To address the second objective, that is, to assess the bioactivity of nitric oxide, we studied the accumulation in tissue of cyclic guanosine 3′,5′-monophosphate (GMP), as well as the acute and chronic effects of withdrawing the nitric oxide vasodilatory tone with the inhibitor of nitric oxide synthesisNG-nitro-L-arginine methyl ester on Wistar–Kyoto rats and spontaneously hypertensive rats.ResultsWe found that the expression of endothelial nitric oxide synthase in the heart, the activity of constitutive nitric oxide synthase in resistance microvessels and the concentration of nitrate in plasma were all significantly higher in the spontaneously hypertensive rats. In contrast, neither cyclic GMP levels nor the effects ofNG-nitro-L-arginine methyl ester were greater in the spontaneously hypertensive rat than they were in the Wistar–Kyoto rat.ConclusionsThe nitric oxide pathway is upregulated in the resistance circulation and the heart of the spontaneously hypertensive rat by a mechanism involving induction of the constitutive nitric oxide synthase and overproduction of nitric oxide. However, nitric oxide is not sufficiently bioactive to stimulate the formation of cyclic GMP and to maintain an adequate nitric oxide-dependent vasodilatory tone.J Hypertens16:609–615 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundMicroneurographic assessment of processed bursts that represent multi-unit nerve discharge has suggested that sympathetic hyperactivity occurs in pregnancy induced hypertension and preeclampsia in comparison with normal pregnancy.ObjectiveTo examine the differences between peripheral sympathetic outputs in pregnancy-induced hypertension and normal pregnancy by directly measuring single impulses of neural discharge.DesignWe compared the sympathetic neural discharge at rest and its reflex responses in subjects with pregnancy-induced hypertension and normal pregnancy and re-examined their progress at least 6 weekspost partum. The patients with pregnancy-induced hypertension were hospital in-patients for whom the diagnosis could be strictly defined and the normally pregnant women were recruited to match the former.MethodsStandard microneurography was performed to quantify single impulses of action potentials, together with the processed multi-unit bursts from fibres innervating the leg muscles. We measured neural discharge with vascular vasoconstrictive properties, heart rate and finger arterial blood pressure at rest and their responses to standard isometric hand-grip exercise and cold pressor tests.ResultsAs expected, patients with pregnancy-induced hypertension (n = 13) had higher levels of finger arterial blood pressure than did women with normal pregnancies (n = 11). The number of single impulses of action potentials (per min and per 100 cardiac beats) in resting patients with pregnancy-induced hypertension was more than three times greater than that in resting women with normal pregnancies, and the number of multi-unit bursts was twofold greater. After delivery of their child, sympathetic activity and heart rate in nine patients decreased, but finger arterial blood pressure decreased in patients with pregnancy-induced hypertension only.ConclusionsFrom results of cross-sectional and longitudinal studies, pregnancy-induced hypertension is associated with a greater resting sympathetic output than that of women with normal pregnancies. Follow-up data after parturition suggest that this hyperactivity is not the only cause of hypertension.J Hypertens16:617–624 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundA reduction in γ-aminobutyric (GABA)-mediated inhibition of pressor sites in the caudal hypothalamus of spontaneously hypertensive rats compared with that of normotensive Wistar–Kyoto rats has recently been demonstrated.ObjectiveTo determine whether the reduction in GABA-mediated inhibition of the caudal hypothalamus of the spontaneously hypertensive rats results from reductions both in the number of GABA-synthesizing neurons and in the amount of the GABA-synthesizing enzyme, glutamic acid decarboxylase messenger RNA (mRNA).Design and methodsA polyclonal antibody (Chemicon) for the 67 kDa isoform of glutamic acid decarboxylase (GAD67) was used to immunocytochemically label GABAergic neurons in the caudal hypothalamus of spontaneously hypertensive and Wistar–Kyoto rats that had been treated beforehand with colchicine. The labeled cells were counted for both strains by a blinded analysis and compared. Caudal hypothalamic tissues from spontaneously hypertensive and Wistar–Kyoto rats were analysed for GAD67mRNA by Northern blotting. The signal intensities of the radioactive probe specific for GAD67for the two strains were analyzed by using a phosphorimager and compared. Control areas for the immunocytochemical (zona incerta) and Northern blotting (cortex, midbrain, cerebellum, and brain stem) experiments were used to determine regional differences in expression of GAD67.ResultsBoth the hypothalamus and cerebellum of spontaneously hypertensive and Wistar–Kyoto rats contained GAD67-immunoreactive neurons; however, there were 42% fewer GAD67neurons in the caudal hypothalamus of spontaneously hypertensive rats than there were in that of Wistar–Kyoto rats. Furthermore, a 33% reduction in the amount of GAD67messenger RNA in the caudal hypothalamus of spontaneously hypertensive rats compared with that for Wistar–Kyoto rats was demonstrated. Analysis of the expression of GAD67in the cortex, midbrain, cerebellum, brain stem, and total brain revealed no difference between spontaneously hypertensive and Wistar–Kyoto rats.ConclusionsOur findings demonstrate that the spontaneously hypertensive rat has fewer neurons synthesizing GABA and less GAD67mRNA in the caudal hypothalamus than do Wistar–Kyoto rats. This deficit in the GABAergic system in the caudal hypothalamus, a wellknown cardiovascular regulatory site, could contribute to the essential hypertension in this animal model.J Hypertens16:625–633 © 1998 Lippincott-Raven Publishers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID