摘要:

Clinical and experimental studies demonstrate that calcium (Ca2+) overload in myocardial cells is an important factor in the genesis of various serious arrhythmias. Calcium antagonists block voltage-dependent channels and thus reduce entry of Ca2+into heart cells. Because of their specificity for atrioventricular nodal cells, verapamil and diltiazem are used clinically to treat supraventricular arrhythmias involving transmission in the atrioventricular node. These two drugs and the dihydropyridine (DHP) calcium antagonists have been shown to prevent ventricular ischemic and reperfusion arrhythmias in the laboratory. Despite these data indicating that calcium antagonists are antiarrhythmic, a recent controversy has raised the possibility that certain calcium antagonists are unsafe to use, especially for patients with coronary heart disease. Proarrhythmia has been proposed to be a mechanism contributing to potentially adverse outcomes. Although excessive concentrations of verapamil and diltiazem may cause sino-atrial nodal asystole and varying degrees of atrioventricular block, there is little direct evidence that this contributes to significant proarrhythmia, for example, ventricular tachyarrhythmias. Nonetheless, although it appears paradoxical that agents which block the entry of Ca2+into heart cells may be considered arrhythmogenic, there are circumstances under which dosage with certain calcium antagonists potentially leads to myocardial Ca2+overload. For example, bouts of neurohormonal activation brought about by calcium antagonist-induced abrupt reductions in blood pressure may be accompanied each time by significant β-adrenergic-enhanced influx of Ca2+through the L-type cardiac calcium channels. This elevates the intracellular Ca2+concentration and disturbs Ca2+regulation, especially in diseased hearts whose intracellular Ca2+regulation has already been compromised, and might induce alterations in cardiac electrical activity. In the present article, interactions among cardiac calcium channels, classes of calcium antagonists, and specific formulations of certain antagonists are considered with respect to directly induced ventricular arrhythmogenesis. Indirect potentially proarrhythmic actions of the calcium antagonists are also discussed. We outline some of the many questions that remain to be answered with respect to the actions of DHP on the heart including that of whether β-adrenergic stimulation modifies the degree of cardiac Ca2+channel inhibition by DHP-type calcium antagonists.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundHypertension is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD), often occurring early in the disease before the renal function starts to decrease. The pathogenesis of this early hypertension is controversial.ObjectiveTo review studies on the pathogenesis of early and late hypertension in ADPKD.Study selectionStudies on ADPKD and hypertension were retrieved from Medline from the last 20 years, with an emphasis on the last 10 years. These studies, together with selected published abstracts from recent hypertension and nephrology meetings, were reviewed critically.ResultsCyst growth, renal handling of sodium, activation of the renin–angiotensin–aldosterone system, volume expansion, an elevated plasma volume, and increased plasma atrial natriuretic peptide and plasma endothelin levels have all been found to be associated with hypertension in ADPKD. In some studies an inappropriate activity of the renin–angiotensin–aldosterone system that could be related to cyst growth and intrarenal ischemia was found. An increase in renal vascular resistance has been demonstrated and might be caused by intrarenal release of angiotensin II. Interestingly, the protective effect of angiotensin converting enzyme inhibitors on the renal function could not be demonstrated in ADPKD patients with a moderately decreased renal function. The importance, if any, of endothelial vasodilatory factors is not known. Sympathetic nervous activity seems to be increased in ADPKD, but the importance of this for the blood pressure level is not known.ConclusionThe pathogenesis of hypertension in ADPKD is complex and likely to be dependent on the interaction of hemodynamic, endocrine and neurogenic factors.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundA cardiac angiotensin II-generating system has been suspected to be involved in various cardiac pathological conditions. Both angiotensin converting enzyme and human chymase can convert angiotensin I to angiotensin II.ObjectiveTo clarify the relative contributions of these two enzymatic pathways to angiotensin II generationin vivo.MethodsWe assessed the expression levels of messenger RNA (mRNA) for collagen type Iα, transforming growth factor-β1, brain natriuretic peptide, angiotensin converting enzyme and chymase in right atrial appendages by competitive polymerase chain reaction and Northern blot analyses. Correlations among the concentrations of these mRNA were analysed to obtain insight that might be important in understanding the formation of angiotensin II in atrial tissue.ResultsThe collagen type Ia and brain natriuretic peptide mRNA concentrations were correlated significantly to the mean pulmonary arterial pressure. Multivariate regression analysis revealed that the collagen type Iα mRNA concentration could be explained in terms of the brain natriuretic peptide (P= 0.0005) and angiotensin converting enzyme (P= 0.0084) mRNA concentrations (r = 0.598,P<0.0001). The chymase mRNA concentration had no significant correlation to the collagen type Ia mRNA concentration. Moreover, multiple regression analysis revealed that the transforming growth factor-β1mRNA concentration could be explained in terms of the angiotensin converting enzyme mRNA concentration alone (r = 0.424,P= 0.014).ConclusionsThe present results suggest that the level of angiotensin converting enzyme affects the tissue angiotensin II level in human atria; however, we could obtain no evidence that chymase is important in determining the tissue angiotensin II level.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo examine the role played by angiotensin II (AII) in the development of prehypertensive vascular hypertrophy in the spontaneously hypertensive rat (SHR) and to determine whether normalization of prehypertensive vascular hypertrophy attenuates the development of hypertension.DesignMale SHR and Wistar–Kyoto (WKY) rats were treated from age 10 days until age 6 weeks with perindopril, an angiotensin converting enzyme (ACE) inhibitor, or with losartan, a type 1 AII receptor antagonist.MethodsAt termination of treatment, or 8 weeks after cessation of treatment, vascular growth was assessed by measurement of hindquarter resistance properties and of the medial cross-sectional area of first-order mesenteric arteries. The growth of the heart was assessed by measurement of the left ventricle: body weight ratio.ResultsPerindopril and losartan treatment of SHR and WKY rats led to a heterogeneous response in the vasculature, resulting in a reduction in perfusion pressures at maximum dilatation and constriction in the hindquarter vasculature but no significant change in medial cross-sectional area of small mesenteric arteries. Neither perindopril nor losartan treatment affected the growth of the left ventricle in the SHR. After the cessation of treatment the development of hypertension in the losartan- and perindopril-treated SHR did not differ from that in controls.ConclusionThese results suggest that AII, acting via angiotensin type 1 receptors, plays an important role in determining the early post-natal reactivity of the hindquarter vasculature but not the medial cross-sectional area of the mesenteric vasculature, which implies that different growth regulatory mechanisms are operating in the two vascular beds. The lack of effect in some vascular beds, together with the lack of effect on the heart, may account for the absence of a persistent effect on the blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundGuanosine 3':5'-cyclic monophosphate (cGMP) is the second messenger of nitric oxide and atrial natriuretic factor, and mediates local vasodilatation. These vasodilatory factors are important in blood pressure regulation and possibly in the etiology of hypertension. Urinary cGMP levels among normotensive young adults have not previously been studied.SubjectsA subset of normotensive participants from the CARDIA study (n = 563), aged 23–35 years, was studied. The sample was approximately balanced for sex and race (black/white).MethodsTwenty-four-hour urinary cGMP levels were measured using an enzyme immunoassay; levels were adjusted for creatinine excretion. The blood pressure, smoking status, and risk factors for hypertension [including a family history of hypertension (FHH), the body mass index, education, alcohol intake, and sodium excretion] were also measured.ResultsWomen excreted more cGMP than did men, and blacks excreted more cGMP than did whites (bothP< 0.0001). Excretion of cGMP was also greater among smokers (P< 0.001) and those with an FHH (P= 0.05), and was related directly and independently to sodium excretion (P< 0.02). The diastolic blood pressure (DBP) was related inversely to the excretion of cGMP among individuals without an FHH (r = −0.36,P< 0.001), but not among individuals with an FHH. In multiple regression analysis, the excretion of cGMP remained related significantly to the DBP and accounted for more variance in DBP than did any other variable among those without an FHH (ΔR2= 0.08,P< 0.001).ConclusionsUrinary cGMP excretion is related inversely and independently to the DBP among those without an FHH but not among those with an FHH, suggesting that cGMP-related vasodilatation is impaired in those with an FHH. Sex differences in urinary excretion of cGMP are consistent with results from studies showing that estrogen increases the endothelial production of nitric oxide.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundThe homozygote deletion (DD) genotype of the angiotensin I converting enzyme (ACE) gene has been shown to be associated with an increased risk of coronary heart disease independent of other risk factors.ObjectiveTo investigate the possible association of the insertion/deletion (I/D) polymorphism of the ACE gene with insulin resistance in a Chinese population with and without hypertension.Subjects and methodsThe I/D polymorphism of the ACE gene was determined for 361 Chinese including 148 women and 96 men with normal blood pressures and 64 male and 53 female patients with mild-to-moderate hypertension. Insulin resistance was estimated by the insulin suppression test and glucose intolerance evaluated with an oral glucose-tolerance test for all of the subjects.ResultsThree hypertensive subgroups with DD, DI and II genotypes having similar ages and body mass indexes presented insignificantly different degrees of glucose intolerance and insulin resistance both among men and among women. Similar results were found for normotensive subjects. In addition, ACE genotypes were not significant predictors of insulin resistance and glucose intolerance either among men or among women after adjustment for age, body mass index, and hypertension.ConclusionThe present data indicated that the I/D polymorphism of the ACE gene was not related to insulin resistance for Chinese hypertensive and normotensive subjects. The increased risk of coronary heart disease associated with the DD genotype need not be mediated through the mechanism of insulin resistance and glucose intolerance for Chinese patients with hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine whether the failure to decrease blood pressure normally during sleep is associated with more prominent target organ damage.MethodsCardiac and vascular structure and function were characterized in 183 asymptomatic, unmedicated hypertensive patients and compared with their ambulatory blood pressures.ResultsThe 104 patients with a normal (> 10%) nocturnal fall in systolic blood pressure (dippers) were similar to the 79 patients with an abnormal fall (nondippers) in sex, race, body size, smoking history, and average awake ambulatory blood pressure. Nondippers tended to be older (57 versus 54 years,P= 0.06). The supine blood pressure upon completion of the ultrasound studies was higher in the nondippers (156/93 versus 146/89 mmHg,P< 0.005) as was the variability of the awake diastolic blood pressure. There were no differences between dippers and nondippers in left ventricular mass (170 versus 172 g), mass index (90 versus 91 gm/m2), prevalence of abnormal ventricular geometry, common carotid artery diameter (5.74 versus 5.75 mm), and vascular strain. Although nondippers were more likely to have carotid artery plaque (41 versus 27%,P= 0.053) and an increased intimal–medial thickness (0.84 versus 0.79 mm,P< 0.05), adjustment for age rendered the differences insignificant. There were no differences in the relation of awake and sleeping systolic pressures to the left ventricular mass (r = 0.36 and 0.35, respectively, bothP< 0.005) or to the carotid wall thickness (r = 0.28 and 0.29, respectively, bothP< 0.005). When the 114 men and 69 women were considered separately, similar findings were obtained. When the 109 whites and 56 blacks (African-Americans and Afro-Caribbeans) were considered separately, there were no differences in left ventricular structure in either group, and differences in vascular structure were confined to the white subgroup.ConclusionThe lack of a normal nocturnal fall in blood pressure is not associated with an increase in left ventricular mass or in arterial disease independently of age. Age-related changes in carotid artery wall thickness and plaque among nondippers may reflect a contribution of an altered baroreceptor function to the lack of normal nocturnal and supine blood pressure decreases.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundPatients with elevated blood pressure levels in the doctor's office but normal blood pressures at other times have recently been described as having ‘isolated office hypertension’ (IOH). There is debate concerning whether this condition is really benign and thus not in need of treatment. Most of the previous studies on this topic included patients who had already been administered antihypertensive treatment, which unavoidably alters their cardiovascular profile.ObjectiveTo evaluate whether recently discovered and never-treated patients with isolated office hypertension have structural or functional abnormalities in comparison with normotensive controls.MethodsPatients included in the study underwent 24 h ambulatory blood pressure monitoring, M-mode echocardiography and high-resolution echography of carotid arteries. Parameters of lipid and carbohydrate metabolism were also determined.ResultsWe investigated 76 patients (20 with IOH and 56 with sustained hypertension) who had recently been diagnosed hypertensive but never been administered antihypertensive treatment and 32 matched controls. No changes were detected in left ventricular mass (LVM h2.7, 41.5 ± 11, 44.5 ± 10 and 41.5 ± 10 g/cm2.7in IOH, sustained hypertension and controls, respectively) and in intimal–medial thickness (IMT, 0.54 ± 0.13, 0.59 ± 0.14 and 0.55 ± 0.16 mm, respectively). However, the left ventricular diastolic function was significantly different (E/A = 1.08 ± 0.3, 1.04 ± 0.3 and 1.43 ± 0.3, respectively,P= 0.02) and the carotid diameter significantly lower than that expected from the pressure–diameter relationship for normotensives.ConclusionsThese results, at variance with those of others, suggest that IOH affects the cardiovascular system even during the early phases of the disease and indicate the need for prospective clinical trials to evaluate the benefit from early treatment of IOH patients.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine the detailed effects of hormone replacement therapy (HRT) on non-invasive haemodynamics, including an assessment of the effect on the pulsatile afterload assessed in terms of the augmentation index and pulse-wave velocity.DesignA cross-sectional study of healthy postmenopausal women using carotid and radial tonometry and pulse-wave velocity measurements.SettingCommunity-based ambulatory women attending the menopause centre at a tertiary hospital.PatientsSeventy postmenopausal women divided into those not currently being administered HRT (n = 38, aged 46–72 years) and those who were being administered a variety of HRT (n = 32, aged 49–67 years).MethodsCentral arterial pressure waveforms were measured using carotid applanation tonometry to derive the augmentation index and ejection duration. The arterial pulse-wave velocity was assessed using paired carotid, radial and dorsalis tonometry waveforms.ResultsWomen being administered HRT had a significantly lower augmentation index (20.4 ± 8.6 versus 27.0 ± 10.2%,P= 0.005) and shorter ejection times (320 ± 17 versus 329 ± 18 ms,P= 0.037). There was no significant difference in brachial blood pressure (131/76 versus 129/77 mmHg). Women being administered HRT exhibited a greater reversal in the age-related loss of amplification which occurs owing to arterial stiffening. This amplification between central and peripheral systolic blood pressures was greater among women being administered HRT (5.3 ± 6.2 versus 2.2 ± 4.0 mmHg,P= 0.014). There was no difference in pulse-wave velocity between the two groups.ConclusionsHRT appears to improve the pulsatile vascular afterload by decreasing the augmentation of the late systolic blood pressure. This effect is not apparent from routine brachial cuff measurements, which, as a result, may underestimate haemodynamic benefits. Such effects may help to explain a portion of the improvement in cardiovascular morbidity found in other trials.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundAn insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene accounts for 50% of the variance in serum ACE activity. ACE is responsible for the generation of angiotensin II, which not only has pressor and mitogenic activities but also exerts effects on left ventricular diastolic performance.ObjectiveTo investigate the contribution of genetic polymorphisms at the ACE gene to the development of diastolic functional abnormalities in 100 patients with essential hypertension.Methods and resultsThe left ventricular mass (LVMI) of each patient was assessed echocardiographically. We calculated peak and integral early: late left ventricular diastolic filling ratios (E: AP, and E: AI, respectively) and determined the ACE genotype from leukocyte DNA. There was no significant difference in age, sex, blood pressure and LVMI among genotype groups. Analysis of covariance modelled for indices of diastolic function, adjusted for age, sex, heart rate and LVMI, demonstrated that the E: APinteracted with age (P< 0.0001), heart rate (P< 0.001) and ACE genotype (P= 0.018). Similarly, the E: AIinteracted with age (P< 0.001), heart rate (P= 0.025) and ACE genotype (P= 0.047). There was a strong correlation between the E: APand the LVMI for the DD group (r = −0.81,P<0.0001) but not for the ID (r = −0.03,P= 0.83) and II (r = −0.23,P= 0.23) groups.ConclusionsThese findings suggest that the I/D polymorphism of the ACE gene influences the relationship between left ventricular mass and echocardiographic left ventricular diastolic filling abnormalities in patients with essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID