ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundBesides hypertension, several cardiovascular risk factors can play a role in the development of coronary heart disease (CHD) in hypertensive patients. Lipoprotein(a) [Lp(a)] is an important and independent cardiovascular risk factor, but its role in the development of CHD in hypertensives has not been studied.ObjectiveTo investigate whether or not Lp(a) levels and isoforms of apolipoprotein(a) [apo(a)] are predictors of CHD in patients with essential hypertension.MethodsLp(a) levels and apo(a) polymorphism were evaluated in 249 patients with essential hypertension, in 142 non-hypertensive patients with CHD and in 264 healthy controls.ResultsHypertensives with CHD (n = 61) had Lp(a) levels [19(range 0.5–73.5) versus 7 mg/dl (range 0–83.5),P< 0.001] and a percentage of apo(a) isoforms of low (< 655 kDa) relative molecular mass (RMM, 59.2 versus 25.9%,P< 0.001) higher than did those without CHD (n = 188). Moreover, there were more subjects with at least one apo(a) isoform of low RMM in the subgroup of patients with CHD than there were in that of those without CHD (80.3 versus 30.8%,P< 0.001). Lp(a) levels and apo(a) polymorphism did not differ significantly between hypertensive and non-hypertensive patients with CHD. Stepwise regression analysis indicated that high Lp(a) levels (P= 0.002073) and particularly the presence of at least one apo(a) isoform of low RMM (P< 0.000001) are strong predictors of CHD in hypertensive patients.ConclusionsOur data show that high Lp(a) levels and the presence of at least one apo(a) isoform of low RMM are strong and independent genetic risk factors for CHD in hypertensive patients. These findings suggest that Lp(a) and apo(a) isoforms should be assessed together with other cardiovascular risk factors to establish the overall CHD risk status of each hypertensive patient.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesTo assess the impact of various criteria used to define hypertension in community surveys on estimates of prevalence, treatment and control. In particular, this paper examines the effect of using mean versus minimum values; one, two or three examinations; and three different blood pressure levels.DesignA cross-sectional community survey.MethodsA multistage area sample of households in Hamilton, Canada was selected, yielding 2770 potential interviewees. Data were obtained from 2140 people (77.2%). About 25% of the sample satisfied the criteria for either one or two follow-up visits (95% completion rate). Estimates of the prevalence of hypertension and its control were computed using 28 different criteria to define hypertension. Estimation methods employed analyses that adjusted for each individual respondent's sampling probability and the effect of area sampling on variance estimates.ResultsThe selection of mean or minimum readings had little impact on the estimates. Prevalence estimates decreased by up to 20% when follow-up information was included but were similar under all three of the studied blood pressure cut-off points. Inclusion of the follow-up information reduced the proportion of hypertensives estimated to be ‘unaware’ of their condition by over 60% while raising the proportion ‘under control’ by around 18%. Application of the Third National Health and Nutrition Examination Survey analysis criteria to the present study demonstrated that alterations in criteria can have profound effects on estimates, the prevalence increasing by about 100% and the proportion ‘unaware’ by 500%. The proportion ‘under control’ dropped from 69.0 to 21.5%.ConclusionsDifferent criteria to define hypertension can have important effects on the estimates of prevalence and control. Authors need to be explicit concerning the criteria used. Readers should be aware of the risk of overinterpreting results based on criteria that do not reflect their objectives (e.g. using a single visit estimate to determine control of clinically relevant hypertension).

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundThe health status of 1999 apparently healthy men, aged 40–59 years, was ascertained after 16 years. We found that their systolic blood pressure during an ergometer exercise test added prognostic information beyond that from their blood pressure at rest concerning total cardiovascular mortality and mortality from myocardial infarction.ObjectiveTo determine predictors of the change in systolic blood pressure at rest during 7 years and of the change in the prognostically important peak exercise systolic blood pressure at 600 kilopondmetres/min during 7 years.MethodsPredictors of the changes in blood pressures were investigated in 1393 middle-aged men who had been healthy without drug treatment for chronic disease or hypertension for 7 years. Twelve potential independent predictors were investigated.ResultsPrevious blood pressures, age and body mass index were independent predictors and could explain 18% of the change in systolic blood pressure at rest over 7 years. For systolic blood pressure at 600 kilopondmetres/min also smoking was associated with a rise whereas a high body mass index, physical fitness and forced expiratory volume in 1 s (allP< 0.001) were associated with lower blood pressure, explaining 19% of the variability.ConclusionsBeyond a relatively strong tracking of blood pressures and the expected effect of age, smoking is associated with a 7-year rise in exercise systolic blood pressure whereas relatively higher body mass, physical fitness and pulmonary function are associated with lower exercise systolic blood pressure after 7 years in middle-aged healthy men.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundReduction in sodium intake improves the survival of stroke-prone spontaneously hypertensive rats (SHR-SP) without causing any change in their blood pressure.ObjectiveTo investigate whether the diuretic indapamide improves survival of SHR-SP and whether changes in the structure and the function of large arteries are associated with survival.Experimental designForty-eight hypertensive rats aged 6 weeks were divided into three groups: a control SHR-SP group (n = 24) and a control spontaneously hypertensive rat (SHR) group (n = 12), with 1% saline drinking water; and an indapamide-treated SHR-SP group (n = 12) with 1% saline drinking water administered 1 mg/kg per day indapamide via their food. At the end of a 12-week follow-up period, pulsatile changes in blood pressure and common carotid artery diameter (measured by high-resolution echo-tracking techniques) were determined and aortic histomorphometry was performed.ResultsBy the end of the study 58% of the SHR-SP control group rats had died. There were no deaths in the other two groups. In these two groups the mean blood pressure (217 ± 10 and 212 ± 7 mmHg), carotid diameter and distensibility (0.48 ± 0.09 and 0.61 ± 0.22 mmHg-1), arterial thickness (116 ± 4 and 116 ± 3 μm), and collagen content of the arterial wall were identical. In the SHR-SP control group the mean blood pressure was significantly lower (168 ± 9 mmHg), the carotid distensibility was higher (1.47 ± 0.35 mmHg-1), and the arterial thickness (138 ± 5 μm) and collagen content were substantially higher than those in the other two groups. In the study population as a whole, for a given mean arterial pressure the carotid distensibility was identical in the three groups, although the arterial thickness was substantially greater in the SHR-SP control group rats.ConclusionsThe study provides evidence that the diuretic compound indapamide improved the survival of SRH-SP even though their blood pressure was higher than that of untreated animals, and that genetic sensitivity to sodium, rather than blood pressure, influences the changes in arterial structure.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundDysfunctional dopamine neurotransmission and defective D1Areceptor–G protein coupling exist in renal proximal tubules (RPT) of the spontaneously hypertensive rat (SHR).ObjectiveTo determine whether the G proteins in SHR are abnormal, preventing formation of agonist high affinity sites in SHR.MethodsWe examined the expression levels of the α-subunits of G proteins, as well as D1Areceptor receptor coupling to exogenously added normal G proteins, in RPT of SHR and the normotensive Wister–Kyoto (WKY) rat.ResultsIn the presence of 110 mmol/l NaCl, the D1Adopamine receptor-selective agonist SKF R-38393 binds both to high- and to low-affinity sites on solubilized and reconstituted D1Areceptors extracted from renal proximal tubules of normotensive Wistar-Kyoto (WKY) rats. In the spontaneously hypertensive rat (SHR), SKF R-38393 bound to a single site on the reconstituted receptor with affinity values corresponding to the low-affinity state of the receptor. Western blot analyses indicated that the α-subunit of the guanine nucleotide binding protein (G-protein), Gs, was expressed at similar levels, whereas Goα was not expressed in proximal tubule membranes from WKY rats and SHR. Pretreatment of proximal tubule membranes with the alkylating agentN-ethylmaleimidein the presence of SKF R-38393 inactivated α-subunitsof endogenous G-proteins, but not D1Areceptors, resulting in loss of high-affinity binding sites in WKY rats. TheseN-ethylmaleimide-treated D1Areceptors from WKY rats, when reconstituted with exogenous sources of G-proteins, were able to couple to these exogenous G-proteins, with complete restoration of high-affinity sites. Moreover, the affinity values and the proportion of these hybrid sites were similar to those of untreated receptors, and these affinity sites were regulated by guanine nucleotide analogs. Reconstitution of D1Areceptors from SHR with the same exogenous G-proteins failed to similarly induce formation of the high-affinity binding sites in the hybrid reconstituted systems, and SKF R-38393 continued to bind in a single low-affinity state of the receptor.ConclusionThese results demonstrate that the absence of G-protein coupling in SHR is due to intrinsic defects within the receptor protein, rather than to any abnormalities of the endogenous G-proteins themselves.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundMetformin treatment of type II diabetes is frequently associated with decreases in blood pressure, an effect that could result from a direct action of metformin on arterial smooth muscle.ObjectiveTo determine the mechanisms responsible for arterial smooth muscle relaxation induced by acute application of metformin and to evaluate the effect of insulin pretreatment on intracellular [Ca2+] ([Ca2+]i) and contraction in an intact artery.MethodsWe stimulated intact deendothelialized rat tail artery with phenylephrine, relaxed the tissue by adding increasing concentrations of metformin, and measured the membrane potential (Em), Mn2+influx, Fura 2-estimated [Ca2+]i, and isometric force. We also evaluated the effect of insulin pretreatment on aequorin-estimated [Ca2+]iin deendothelialized swine carotid artery.ResultsIn rat tail artery we found that a high concentration of metformin-induced repolarization associated with proportional decreases in Mn2+influx, Fura 2-estimated [Ca2+]i, and isometric force. Incubation of swine carotid artery in 100 mU/ml insulin for 30 min or overnight (16–22 h) did not significantly alter histamine or high-K+-induced increases in [Ca2+]ior contraction.ConclusionThese data suggest that acute administration of high concentrations of metformin induces rat tail artery relaxation primarily by repolarization. Additionally, we found that insulin was not vasoactive in the swine carotid artery. It is possible that insulin may alter [Ca2+]ihandling in other arteries, in other species, or only in cultured smooth muscle.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine the cell cycle specificity and intracellular mechanisms involved in inhibition by nitric oxide (NO) of vascular smooth muscle cell mitogenesis.MethodsCultured rat aortic smooth muscle cells were synchronized by serum withdrawal, treated with the NO donorS-nitroso-N-acetylpenicillamine and the cyclic GMP analog 8-Br-cGMP at various times during cell cycle progression, and DNA synthesis measured during the S phase. Two additional NO donors, 5-nitroso-glutathione and diethylamine NONOate, were used to confirm the inhibition of DNA synthesis byS-nitroso-N-acetylpenicillamine, and the ability of two antagonists of free NO to reverse the effects of NO donors was also evaluated. Bypass of ribonucleotide reductase by use of exogenous deoxynucleosides was attempted to determine whether inhibition of this S-phase enzyme was the mechanism by which NO inhibited DNA synthesis during the S phase.ResultsVascular smooth muscle cell mitogenesis was inhibited by cyclic GMP (cGMP) up to late G1phase of the cell cycle, which corresponded to the point of greatest sensitivity to exogenous NO. In contrast to cGMP, three different NO donors inhibited DNA synthesis when added to cells synchronized in S phase, beyond the restriction point of cell cycle control in late G1phase. This S-phase inhibition was reversible by removal of the NO donor or addition of two NO antagonists and was not observed with non-NO analogs of the donors. Inhibition by NO donors in S phase was neither reversed by the guanylate cyclase inhibitor methylene blue nor mimicked by exogenous cGMP. The S-phase inhibition by all three NO donors was reversed partially by bypass of ribonucleotide reductase, establishing this enzyme as an S-phase target of NO.ConclusionsThese findings demonstrate that NO inhibits smooth muscle mitogenesis by cGMP-dependent and -independent mechanisms acting at distinct points in the cell cycle. NO is the first endogenous substance to have been shown to inhibit mitogenesis beyond the restriction point in late G1phase, suggesting that it plays a role in regulation of cells that have lost normal mechanisms of G1growth control, such as the hyperproliferative smooth muscle cells noted in hypertension and restenosis.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo examine effects of intracerebroventricular (ICV) administration of metformin on the responses to environmental stress and on arterial baroreflex function in conscious spontaneously hypertensive rats (SHR).MethodsSHR were instrumented with an ICV cannula and prepared for measurements of the mean arterial pressure (MAP), heart rate, and renal sympathetic nerve activity (RSNA) during air-jet stress (AJS). After recovery from a pretreatment AJS period, rats were allocated randomly to ICV administration of either vehicle (saline; n = 9) or 1 mg metformin (which is inactive dose after intravenous administration; n = 8). After stabilization for 1 h, the AJS was repeated. The arterial baroreflex control of the heart rate and RSNA was examined at the end of the experiment.ResultsICV metformin decreased the baseline heart rate (by 88 ± 14 beats/min) and RSNA (by 19 ± 8%) in the absence of changes in MAP. ICV vehicle did not affect responses to the AJS [change in MAP (ΔMAP) = +11 ± 2 mmHg, change in heart rate (ΔHR) = +54 ± 9 beats/min, change in RSNA (ΔRSNA) = +37 ± 8%), but pressor, tachycardic, and renal sympathoexcitatory responses to the AJS were inhibited significantly by ICV metformin (ΔMAP = +4 ± 3 mmHg, ΔHR = −5 ± 5 beats/min; ΔRSNA = +11 ± 3%). ICV metformin did not affect the arterial baroreflex range, but it did increase the maximal gain of the arterial baroreflex control of heart rate (−1.46 ± 0.25 versus 0.67 ± 0.13%/mmHg,P= 0.01) and RSNA (−5.04 ± 1.10 versus −2.47 ± 0.28%/mmHg,P= 0.053).ConclusionsCentral metformin administration attenuated the renal sympathoexcitatory response to environmental stress and increased the gain of the arterial baroreflex control of heart rate and RSNA. These actions may contribute to the antihypertensive effect of metformin.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID