摘要:

Systemic arterial hypertension is one of the major risk factors for coronary artery disease, coronary microangiopathy, and left ventricular hypertrophy, all of which can potentially lead to cardiac failure and sudden cardiac death. Coronary flow reserve is defined as the maximal increase in coronary flow above its resting, autoregulated level for a given perfusion pressure. In arterial hypertension functional and structural alterations are observed at the level of epicardial vessels as well as in resistive vessels requiring sophisticated approaches to assess coronary flow reserve and thus myocardial perfusion. Electrocardiographic tests and echocardiography can be regarded as monitoring and screening methods. Myocardial scintography is useful to semiquantitatively estimate hypertension-associated perfusion abnormalities, whereas positron emission tomography provides the only quantitative approach of a non-invasive technique for myocardial blood flow measurement. Invasive methods for the assessment of coronary blood flow need cardiac catheterization procedures, such as techniques requiring catheterization of the coronary sinus, angiographic methods, and guide-wire based methods. Thermodilution and venous oxymetry in the coronary sinus systematically underestimate coronary flow reserve and are thus considered as only semiquantitative approaches. In contrast, the gas chromatographic argon method allows a quantitative measurement of coronary blood flow at baseline and during maximum vasodilation; thus it is possible to distinguish between an altered autoregulated and maximal flow as the major cause of a reduced coronary flow reserve and to evaluate long-term therapeutic interventions in hypertensive hearts. Videodensitometric and angiographic methods should be restricted only to patients with coronary microangiopathy or with coronary single-vessel disease. Guidewire-based Doppler techniques are suitable to semiquantitatively assess coronary flow reserve with a considerable spatial and time resolution. Myocardial biopsies may gain insight into hypertension-associated structural alterations in small arterioles. Long-term treatment of hypertensive heart disease aims to normalize blood pressure, to reduce left ventricular hypertrophy and to achieve cardioreparation including reversal of the abnormal structure and function of coronary circulation. Based on the different methods for assessment of coronary circulation the therapeutic value of different classes of antihypertensive therapeutics will be evaluated in this overview.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo examine the relationship between mortality and diastolic blood pressure during treatment.DesignA prospective follow-up of a population-based dynamic cohort of hypertensive patients.SettingProvince of North Karelia, eastern Finland.PatientsA cohort of 16 913 North Karelian hypertensive patients in hypertension register of the North Karelia Project, who had been followed up since 1972 until the end of 1985. Most of these patients had been under antihypertensive drug therapy during the follow-up.Main outcome measuresDeath: all deaths (n = 4490), deaths from cardiovascular disease (n = 2995) and deaths from non-cardiovascular disease (n = 1495).ResultsOf all deaths, 17% of those among men and 24% of those among women were of patients with mean diastolic blood pressures less than 90 mmHg. We found a U-shaped relationship between diastolic blood pressure and total, cardiovascular and non-cardiovascular mortalities. We investigated this relationship in more detail using Cox regression model. Low diastolic blood pressure was associated independently with increased mortality for the patients aged 50 years or more at baseline. The occurrence of cardiac failure and other cardiovascular complications of hypertension were more important determinants of mortality than was low diastolic blood pressure alone.ConclusionsWe demonstrated that there is an association between low diastolic blood pressure and mortality for treated hypertensive patients aged 50–69 years. The clinical importance of this relationship for patients without any cardiovascular complications of hypertension seems negligible. For patients with complications, these complications are likely to be primary factors causing greater than normal mortality and low diastolic blood pressure is mostly a secondary phenomenon. Our data do not lend support to speculations that there is overtreatment of hypertension, which would increase mortality through making diastolic blood pressures too low.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo evaluate the influence of heredity on blood pressure levels and reactivity in the offspring of borderline hypertensive and normotensive fathers.Participants and outcome measuresBorderline hypertensive and normotensive men having normotensive wives (n = 25 and 26) were identified in a population screening program. Their children aged above 12 years were invited to participate. Seventeen having a borderline hypertensive father (BHT+) and 19 with a normotensive father (NT+) were investigated. Clinical and 24 h ambulatory blood pressure was measured, as well as blood pressure reactivity to an arithmetic mental stress test.ResultsThe BHT+ group had a significantly higher clinical systolic blood pressure than the NT+ group (126 ± 13 versus 115 ± 7 mmHg,P< 0.01) but similar 24 h blood pressure levels. Systolic blood pressure variability (standard deviation of systolic blood pressure measurements each hour over 24 h) was significantly higher in the BHT+ group (18 ± 4 versus 16 ± 4 mmHg,P< 0.05). During mental stress test the BHT+ group had significantly higher increases in systolic and diastolic blood pressures at 4 min (NT+ 8% and 13% versus BHT+ 16% and 23% above baseline,P< 0.05) and significantly elevated DBP during the period after the stress test (NT+ 1% versus BHT+ 13% above baseline,P< 0.01).ConclusionEven a mild level of hypertensive heredity affects important markers of blood pressure regulation, such as blood pressure variability and reactivity to mental stress. This might have prognostic implications; it also points to the possible importance of these variables as early signs of a familial predisposition to hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo determine whether the development of arterial hypertension due to occlusion of the central adrenal vein in the rat is strain-dependent.Design and methodsThe experiments were performed on male rats weighing 300–400 g each, of the following strains: Wistar outbred, Wistar Glaxo, Lewis, Wistar–Kyoto (WKY) rats bred for high blood pressure (138 ± 13.2 mmHg), WKY rats bred without the control of blood pressure (118 ± 12.9 mmHg) and borderline hypertensive rats (BHR). BHR were the F1spontaneously hypertensive rat and WKY rat crossbred rats. In order to increase blood flow through the adrenal-renal portal circulation, both central adrenal veins of rats in the experimental group were occluded. The systolic blood pressure was measured indirectly by a photoelectric method.ResultsBy the ninth day after surgery systolic blood pressure had increased significantly only in the WKY rats bred for high blood pressure and BHR, reaching maximal values on 12th day for WKY rats bred for high blood pressure (167 ± 5 mmHg) and on the 18th day for BHR (170 ± 14 mmHg).ConclusionsThese data show that the development of arterial hypertension due to augmentation of adrenal blood flow through adrenal–renal portal circulation occurs in rats of strains with a genetic background of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThe aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives.Design and methodsWe performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (≤ 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects.ResultsPlasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups.ConclusionsOur results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesCarboxyl methylation is a reversible post-translational event which regulates the function of several cellular proteins. Because the human Na+–H+antiporter (NHE-1) possesses a C-terminal consensus sequence for carboxyl methylation, we examined the role of protein carboxyl methylation in the regulation of intracellular pH homeostasis.DesignExperiments were conducted using human platelets andN-acetyl-S-trans, trans-farnesyl-L cysteine (AFC), a specific prenylcysteine methyltransferase inhibitor. The effect of AFC on both basal intracellular pH (pHi) and on the kinetic properties of the Na+–H+antiporter was characterized.Materials and methodspHi was determined in cell suspensions using 2,7-biscarboxyethyl-5(6)-carboxy-fluorescein tetraacetoxymethyl ester, a fluorescent pH indicator. The kinetics properties of the Na+–H+antiporter activity were determined using platelets acidified with nigericin and challenged with varying extracellular concentrations of Na+.ResultsAFC (20 μmol/l) decreased basal pHisignificantly (7.047 ± 0.011 versus 7.133 ± 0.012 for control,P< 0.001). The acidification was dose-dependent and reached steady state 3 min after AFC addition. In the absence of extracellular Na+, the platelets were acidified to the same extent with AFC or with ethanol (control): 6.530 ± 0.031 versus 6.532 ± 0.031 (P= 0.97). However, upon addition of Na+, the platelets treated with AFC showed a significant decrease in the maximal value for initial pHirecovery compared with controls: 0.788 ± 0.041 versus 0.983 ± 0.047 pH/min (P< 0.02). AFC also increased the Hill coefficient (2.89 ± 0.22 versus 2.14 ± 0.16,P< 0.03), and tended to decrease K0.5, the [Na+] corresponding to half-maximal activation (51.3 ± 1.8 versus 60.5 ± 3.9 μmol/l,P= 0.06) of the antiporter.ConclusionOur data indicate that inhibition of carboxyl methylation reduces basal pHiand alters the kinetic properties of the Na+–H+antiporter in human platelets, suggesting that carboxyl methylation is implicated in the regulation of intracellular pH homeostasis.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundLipid peroxidation and derived oxidized products are being intensively investigated, because of their potential to cause injury and their pathogenetic role in several clinically significant diseases. The view that an excess of lipid peroxidation products is present and relevant in the pathogenesis of human essential hypertension or in hypertension-induced damage has still not received definitive support.ObjectiveTo evaluate both the extent of lipoperoxidation in essential hypertensive patients and the status of enzymatic and non-enzymatic antioxidants that potentially are able to modulate it.MethodsWe selected 105 newly diagnosed essential hypertensives among those referred to our hypertension outpatient clinic and compared them with 100 normotensive controls matched for age. Plasma malondialdehyde was measured by high-performance liquid chromatography after reaction with thiobarbituric acid, as an end product of lipid peroxidation; serum selenium (Se), plasma copper (Cu) and zinc (Zn), vitamins A and E, erythrocyte superoxide dismutase and glutathione peroxidase levels were evaluated as indices of oxidant balance. Differences between the groups were tested by Student's t test and χ2test.ResultsCompared with controls, essential hypertension patients had higher malondialdehyde and glutathione peroxidase activities (P< 0.05 for both) and Zn concentrations (P< 0.001) and lower superoxide dismutase activities (P< 0.005), vitamin A (P< 0.05) and E (P< 0.001) levels and Cu concentrations (P< 0.005). We found no difference between Se levels of essential hypertensive and control subjects.ConclusionsEssential hypertension is associated with greater than normal lipoperoxidation and an imbalance in anti-oxidant status, suggesting that oxidative stress is important in the pathogenesis of essential hypertension or in arterial damage related to essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThe hypertensive state is often associated with metabolic abnormalities, including glucose intolerance. Tissue kallikrein, a potent kinin-generating enzyme, is present in the vascular wall and heart tissue. High dietary fructose consumption is reported to induce hyperinsulinemia, hypertriglyceridemia and hypertension. The objective of the present study was to examine the status of kallikrein in vascular and cardiac tissue from highly fructose-fed rats and to delineate the effect of kinins and the angiotensin converting enzyme inhibitor ramipril in this animal model of glucose intolerance.Design and methodsMale Wistar rats (350 g body weight) were divided into four groups of 10 rats each: (1) controls; (2) oral ramipril at 500 μg/kg per day for the last 2 study weeks; (3) fructose in drinking water as a 10% (w/v) solution for 4 weeks; and (4) fructose + ramipril, with fructose administered as in group 3 plus the administration of ramipril for the last 2 study weeks. Systolic blood pressure (tail-cuff method), glucose tolerance (2 g/kg body weight intraperitoneally) and metabolic parameters were recorded. Kallikrein activity in tail artery and heart tissue homogenates was estimated at the end of the 4th study week from measurements of kininogenase activity and kinins generated by a radioimmunoassay.ResultsThe area under the curve for the glucose tolerance testincreased from 1265 ± 103 mmol/l after 120 min in the control and 1152 ± 36 mmol/l in the ramipril group (NS) to 2628 ± 143 mmol/l in the fructose group (P< 0.01). The administration of ramipril to fructose-treated rats in group 4 improved glucose tolerance (2160 ± 100 mmol/l;P< 0.05 versus group 3). Blood pressure increased significantly in fructose-fed rats but fell markedly in fructose-fed rats treated with ramipril (P< 0.01). Kallikrein activity measured in the heart and vessels increased as a consequence of fructose administration (P< 0.05), but the administration of ramipril increased this parameter to a much greater extent (P< 0.01 versus control group), which correlated closely with the decrease in blood pressure and the improvement in glucose tolerance observed in the fructose + ramipril group.ConclusionsThe administration of fructose as a solution in the drinking water induced glucose intolerance and increased blood pressure. Treatment with the angiotensin converting enzyme inhibitor ramipril improved glucose tolerance and significantly diminished blood pressure. Cardiovascular kinin-generating capability increased in treated animals and this increase was even higher when rats were treated with ramipril, suggesting that kinins, acting as a paracrine hormonal system, can exert cardiovascular protection and contribute to the beneficial effects of angiotensin converting enzyme inhibitor.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesElevated plasma endothelin (ET)-1 levels have been described in insulin-resistant states such as syndrome X, obesity, non-insulin-dependent diabetes mellitus, and in some studies in essential hypertension. To investigate whether increases in circulating ET-1 to levels observed in insulin-resistant states can modulate insulin levels and/or insulin sensitivity in humans, we assessed these variables during low, non-pressor-dose ET-1 compared with placebo infusion.DesignIn a randomized, single blind, crossover design, 10 lean normotensive male subjects received either an intravenous infusion of subpressor doses of ET-1 dissolved in polygeline or a control infusion of polygeline only (placebo). Using dynamic assessment by the minimal model approach with the modified frequent sampling intravenous glucose tolerance test (FSIGT) the following and other parameters were measured: insulin sensitivity; acute insulin response to glucose (AIRG) calculated as the average of the three peak values between 2 and 5 min after injection of glucose from which the basal insulin levels were substracted; the initial area under the curve (AUC1-19) from insulin values between time 0 and 19 min and the first-phase insulin secretion (&phis;1) from insulin kinetics parameters.ResultsET-1 infusion reduced AIRG (to 34.85 ± 4.27 compared with 49.3 ± 6.9 μU/ml during placebo,P= 0.017) and the acute C-peptide response to glucose (to 2.33 ± 0.41 compared with 3.1 ± 0.44 ng/ml,P= 0.018), decreased plasma insulin levels during the FSIGT compared with placebo (analysis of varianceP< 0.0001) and decreased the AUC1-19(to 2.1 ± 0.2 compared with 2.9 ± 0.3 U/l per 20 min,P< 0.01) while f1 tended to be lower. SImeasured during ET-1 infusion was unaltered (11.11 ± 1.91 × 10-4versus 10.88 ± 2.11 10-4/min per mU per l, NS).ConclusionsThese findings demonstrate that an increase in circulating ET-1 to levels observed in insulin-resistant states acutely diminishes the insulin secretory response but does not significantly modify insulin sensitivity.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo investigate whether plasma angiotensin II (Ang II) determines the effects of the renin-angiotensin system or whether tissue uptake of renin and localized production of Ang II might account for any cardiovascular, renal, hormonal or drinking effect of circulating renin.DesignIntravenous infusions of renin (0.6 ng/min; n = 10) and Ang II (3.5 ng/min; n = 10) that produce similar plasma Ang II levels were compared for 2 weeks with vehicle (n = 7) in conscious rats after a 1-week control period. Mean arterial pressure (MAP) and the heart rate were measured continuously. Hormones and renal function were measured twice weekly. Plasma Ang II and recovery data were measured in seven additional rats.ResultsIn renin and Ang II-infused rats, respectively, plasma Ang II increased similarly from 4.5 ± 0.8 and 4.4 ± 0.9 to 10.8 ± 0.7 and 10.6 ± 0.7 pg/ml and declined similarly in the second week to 7.0 ± 1.1 and 7.0 ± 1.5 pg/ml. Plasma renin increased from 4.2 ± 0.7 to 21.7 ± 1.3 and fell from 5.9 ± 0.5 to 0.6 ± 0.2 ng/ml per h respectively. Plasma prorenin fell similarly (> 70%); angiotensinogen was unchanged. MAP rose initially by 25.6 ± 1.2 and 23.3 ± 0.9 mmHg and by an additional 21.1 ± 2.4 and 27.4 ± 1.8 mmHg on days 5–8. The heart rate fell gradually but transiently by -11% in both. Although the initial MAP rise was slower in renin-infused rats (P< 0.05) MAP returned to baseline within 2 h after both infusions were stopped. Changes in renal vascular resistance, renal blood flow, glomerular filtration rate, urinary sodium, potassium and water excretion and water intake were not significantly different between renin-and Ang II-infused rats.ConclusionsIntravenous infusions of low doses of renin or Ang II into conscious rats increase MAP identically. MAP increases in two phases 5–8 days apart, in coordination with transient falls in the heart rate. Reninand Ang II-induced chronic hypertension are identically sustained by very small increases in plasma Ang II. Blood pressure increases more slowly with renin infusions, consistent with tissue binding. Notwithstanding, no evidence was obtained for a physiological role of tissue-bound renin in causing the cardiovascular, renal, hormonal and drinking responses measured in this study.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID