高血压患者压力反射敏感性与部分内分泌激素的相关性研究

目的：为探讨原发性高血压（EH）患者压力反射敏感性（BRS）与部分内分泌激素之间的相关性。方法：应用无创被动倾斜方法估测43例EH患者及30例正常人在60°被动倾斜前后血压、心率变化，心电图上第30个心动周期与第15个心动周期的卜R间期的比值（30：15比值）及BRS值；同时测定部分患者（20例）及正常人（10例）静息状态下血浆儿茶酚胺（CA）、心钠素（ANP）、内皮素（ET）及一氧化氮（NO）浓度，并与BRS值进行直线相关分析。结果：EH患者BRS明显低于正常人（P＜0．01）且与病期、病情相关；BRS与去甲肾上腺素显著负相关（r=－0．56，P＜0．01），而与肾上腺素、ANP、ET及NO无相关。结论：EH患者的BRS明显衰减，并与EH的发生发展相平行；交感神经系统的CA参与高血压的压力反射调节；ANP、ET及NO对压力反射功能的影响有待于进一步探讨。     

Relationship between natriuresis and changes in plasma atrial natriuretic factor, renin activity and aldosterone levels in fasting obese subjects

This study was conducted to assess whether changes in atrial natriuretic factor (ANF) secretion could account for the natriuresis of the early phase of fasting. To this end, 8 AM (supine) and 10 AM (standing) plasma ANF concentrations were determined daily and compared with plasma renin activity and aldosterone levels in 8 obese subjects submitted to a 7-day total fast. Depiste constant daily sodium intake (51 mmol), urinary sodium excretion increased from 35 +/- 7 to 109 +/- 8 mmol/day after 4 days of fast (p less than 0.001) and declined thereafter. Urinary ketone excretion progressively increased over the whole period of fasting (p less than 0.001). Interestingly, fasting induced a decrease in plasma ANF concentrations (p less than 0.05). A contrast analysis revealed no significant change in ANF during the initial natriuretic phase of fasting but a decrease at the end of fasting averaging 36% (p less than 0.05) and 18% (p less than 0.05) at 8 and 10 AM respectively. In contrast, plasma aldosterone rose during fasting (p less than 0.05), the difference being significant at the end of fasting (p less than 0.01). Plasma renin activity and cortisol did not change significantly over the fasting period. Postural and/or diurnal changes of ANF, aldosterone, renin and cortisol were preserved during fasting (p less than 0.01). Postural changes of ANF were, however, attenuated at the end of fasting (p less than 0.05). These data indicate that the fasting natriuresis cannot be explained by changes in ANF levels but that the loss of sodium may contribute to a decline of basal ANF levels, with an attenuation of their physiological postural changes, and to a stimulation of the aldosterone secretion.     

Relationship between sympathetic baroreflex sensitivity and arterial stiffness in elderly men and women

Previous human studies have shown that large-artery stiffness contributes to an age-related decrease in cardiovagal baroreflex sensitivity. Whether this is also true with sympathetic baroreflex sensitivity is unknown. We tested the hypothesis that sympathetic baroreflex sensitivity is associated with the stiffness of baroreceptor segments (the carotid artery and the aorta) in elderly individuals and that sex affects this relationship. Sympathetic baroreflex sensitivity was assessed from the spontaneous changes in beat-by-beat diastolic pressure and corresponding muscle sympathetic nerve activity (microneurography) during supine rest in 30 men (mean±SEM: 69±1 years) and 31 women (68±1 years). Carotid artery stiffness (B-mode ultrasonography) and aortic stiffness (MRI) were also determined. We found that elderly women had lower sympathetic baroreflex sensitivity than elderly men (-2.33±0.25 versus -3.32±0.25 bursts · 100 beats(-1) · mm Hg(-1); P=0.007). β-Stiffness indices of the carotid artery and the aorta were greater in elderly women than in men (6.68±0.48 versus 5.10±0.50 and 4.03±0.47 versus 2.68±0.42; both P<0.050). Sympathetic baroreflex sensitivity was inversely correlated with carotid artery stiffness in both men and women (r=0.49 and 0.50; both P<0.05), whereas this relation was shifted in parallel upward (toward a reduced sensitivity) in women with no changes in the slope (0.26 versus 0.24 arbitrary units). Sympathetic baroreflex sensitivity and aortic stiffness showed similar trends. Thus, barosensory artery stiffness seems to be one independent determinant of sympathetic baroreflex sensitivity in elderly men and women. The lower sympathetic baroreflex sensitivity in elderly women may predispose them to an increased prevalence of hypertension.     

Contribution of prostaglandins to pressure natriuresis in Dahl salt-sensitive rats.

To examine the role of prostaglandins on pressure natriuresis in Dahl salt-sensitive (DS) rat, the pressure-natriuresis relationships in DS and Dahl salt-resistant (DR) rats were characterized with or without indomethacin (2 mg/kg/h) by utilizing an in vivo renal perfusion study. When untreated, in the DS rat the pressure-natriuresis curve was blunted (P less than .05) and excretion of prostaglandin E2 (38 +/- 11 to 109 +/- 43 pg/min) was decreased in comparison to the DR rat. With indomethacin, the pressure-natriuresis curve in the DR rat was blunted, while no significant changes were observed in the DS rat. Plasma renin activity and concentration of atrial natriuretic peptide were not changed by the treatment of indomethacin in both strains. These results suggest that the decrease in renal prostaglandins, at least in prostaglandin E2, plays some role in blunting pressure natriuresis in DS rat.     

Relationship between molecular weight conversion and renin activity in dog renal renin.

A normal size form of renin, which seems to be a storage form in renin granules, changed neither in molecular weight nor activity by acidification to pH 3.0. High molecular weight (HMW) renin fractionated by gel chromatography from crude renal extract prepared with thiol group blockers was converted into normal size renin by acdification, accompanied with an increase in renin activity by about 50%. The molecular weight conversion by acidification appeared due to destruction or loss of binding ability of the renin binding substance which was present in the cytosol of renal cortical tissue. Renin and renin binding substance could combine into HMW renin at neutral pH in the presence of thiol group blockers and renin activity decreased.     

Exaggerated natriuresis after selective AT1 receptor blockade in Dahl salt-sensitive rats.

Salt-sensitive individuals are susceptible to develop hypertension when exposed to high salt-diet. Such a phenomenon is considered to be due to a genetic impairment in the renal excretion of sodium. In the present studies extent of endogenous angiotensin-II (Ang-II) mediated antinatriuresis was comparatively evaluated in Dahl salt-sensitive (SS) and salt-resistant (SR) rats, using a selective AT1 receptor antagonist, candesartan. In addition, differences in plasma renin activity and characteristics of Ang-II receptors in the renal cortical tubular membranes were also examined. Under INACTIN anesthesia AT1 receptor blockade resulted in significant increases in renal sodium excretion, which was several-fold greater in SS rats than that observed in SR rats. These observations suggest that antinatriuretic function of endogenous angiotensin-II is exaggerated in SS rats. This functional overexpression appears to be related to an increase in the affinity of Ang-II receptors in renal cortical tubular membranes but not to receptor density or plasma renin activity. It is proposed that salt-dependent hypertension in Dahl salt-sensitive rats may be due to enhanced Ang-II mediated sodium retention.     

Relationship of baroreflex sensitivity and blood pressure in an older population

OBJECTIVES: Ageing and hypertension are associated with reduced baroreflex sensitivity (BRS) in young and middle-aged populations. The effects of blood pressure level on BRS in the older population are unclear. We examined the association between blood pressure and BRS in older persons with blood pressure below 180 mmHg. METHODS: BRS, high (alphaHF 0.15-0.4 Hz) and low (alphaLF 0.04-0.15 Hz) frequency alpha-index, was determined in 75 normotensive subjects (aged 75 +/- 4 years, 41% female, 131 +/- 10/74 +/- 7 mmHg) and 64 untreated hypertensive subjects (aged 76 +/- 5 years, 48% female, 165 +/- 7/ 88 +/- 7 mmHg) by spectral analysis of 20 min continuous blood pressure and heart rate recordings using finger plethysmography. Subjects were recruited from 10 general practices and were taking no cardiovascular medications. RESULTS: High but not low frequency alpha-index was significantly blunted in hypertensive subjects (alphaHF 5.1 +/- 3.1 versus 8.4 +/- 7.4 ms/mmHg, P< 0.001 and alphaLF 4.7 +/- 3.0 versus 5.8 +/- 3.9 ms/mmHg, P= 0.07). Multivariate analysis of the relationship between age and blood pressure demonstrated systolic and to a lesser extent diastolic blood pressure were significant predictors of variance in BRS for alphaHF [systolic blood pressure (SBP) P< 0.0001, diastolic blood pressure (DBP) P< 0.05, r2 = 0.1] and alphaLF (SBP P=0.01, DBP P<0.05, r2 = 0.04). Age was not a significant predictor for either measure, in the 20 year range studied. CONCLUSIONS: In an older population blood pressure is associated with reduced BRS, particularly for the high frequency component. Such a change may place older subjects with hypertension at increased risk of orthostatic hypotension, vasovagal syncope and sudden cardiac death.     

盐阈、盐摄入量与血压盐敏感性的关系研究

目的探讨盐阈、盐摄入量与血压盐敏感性之间的关系。方法选取203人进行慢性盐负荷试验,确定盐敏感性,并测定其盐阈、收集基线24h尿液,测定尿钠排泄量。结果盐敏感者检出率为19.2%。盐敏感与盐不敏感者之间盐阈、24小时尿钠排泄量差异无统计学意义;无论盐敏感者还是盐不敏感者,盐阈与24h尿钠排泄量有显著相关性。结论盐敏感者钠盐摄入量并不比盐不敏感者高;盐敏感者长期高盐饮食,才可能表现出盐与血压的联系,发生高血压。     

Diastolic dysfunction and baroreflex sensitivity in hypertension.

The determinants of diastolic dysfunction in patients with systemic hypertension are not completely known. To evaluate the possible role of age, arterial blood pressure, and baroreflex heart rate response impairment in causing diastolic dysfunction, we studied 61 patients (42 male; mean+/-SD age, 43.9+/-12 years) with newly recognized and therefore previously untreated systemic hypertension. Diastolic dysfunction was evaluated by means of Doppler echocardiography (and diagnosed as such when the early to atrial peak velocity ratio corrected to heart rate was <1), arterial blood pressure by 24-hour ambulatory monitoring, and baroreflex heart rate response by means of the spectral technique (alpha index) during paced (0.27 Hz) and spontaneous breathing (in a supine position and during tilt). Nineteen patients had diastolic dysfunction, the most powerful predictor of which was age (r=-0.63, P<0.001). The patients with diastolic dysfunction had significantly lower values for spectral baroreflex gain in the high-frequency band than those without (5.2+/-3 versus 8.4+/-5 ms/mm Hg during paced breathing, P<0.05; 7. 4+/-4 versus 13.3+/-7 ms/mm Hg in a supine position, P<0.05; 4.3+/-4 versus 5+/-2 ms/mm Hg during tilt, P相似文献   

Suppression of adrenal renin in Dahl salt-sensitive rats

We previously showed that adrenal renin is highest in the rat zona glomerulosa (ZG) and that low sodium or high potassium and nephrectomy increase adrenal ZG renin and aldosterone. Dahl salt-sensitive rats (S) have been shown to have lower plasma renin activity and plasma aldosterone and higher plasma 18-hydroxy-11-deoxycorticosterone than Dahl salt-resistant rats (R). In this study we assess the possible role of adrenal ZG renin in the suppression of aldosterone in S rats. Adrenal ZG renin was significantly decreased in S as compared with R rats even at 6 weeks of age, when both S and R rats are still normotensive (S = 7.2 +/- 0.2, R = 18.0 +/- 1.6 ng angiotensin I/mg protein/hr). Adrenal ZG aldosterone was also significantly lower in S than in R rats (S = 21.1 +/- 4.3, R = 39.5 +/- 3.6 ng/mg protein). Furthermore, the rise in adrenal ZG renin and aldosterone after nephrectomy in S rats was significantly less than that in R rats. To determine if the suppressed adrenal ZG renin of S rats is due to volume expansion, we studied the effect of a sodium-deficient diet on adrenal ZG renin in S and R rats. After 2 weeks of a sodium-deficient diet S rats had significantly lower basal adrenal ZG renin than did R rats (S = 7.6 +/- 0.4, R = 21.7 +/- 1.9 ng angiotensin I/mg protein/hr) and a marked blunting of the adrenal ZG renin response to nephrectomy (S = 13.6 +/- 1.1, DR = 167 +/- 16.1 ng angiotensin I/mg protein/hr).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between renin mRNA and renin secretion in adrenalectomized, salt-depleted, or converting enzyme inhibitor-treated rats

Renin secretion was stimulated in rats by adrenalectomy (ADX), by treatment with the converting enzyme inhibitor enalapril (MK 421), or by feeding a low salt diet plus furosemide treatment (FUR). Relative amounts of renin mRNA were measured by densitometric Northern blot analysis using a ³²P-labeled 700 bp mouse submaxillary gland cDNA fragment as hybridization probe. Renin secretion was measured in isolated kidneys taken from pretreated rats. Treatment resulted in a 4.4-, 7- and 12.7-fold increase in total renin mRNA in kidneys of ADX, MK 421 and FUR rats, respectively. Plasma renin levels increased 5-, 9- and 12-fold in ADX, MK 421 and FUR rats, whereas ex vivo secretion rates from the isolated kidney were 4.7-, 0.5- and 4.2-fold, respectively, that of controls. Thus, a close relationship between increases in renin secretion in vivo (reflected by plasma renin concentration) and renin mRNA exists, whereas secretion rates in the isolated perfused kidney ex vivo change in a non-proportional fashion.     

Cardiac baroreflex sensitivity is not correlated to sympathetic baroreflex sensitivity within healthy, young humans

The purpose of this study was to evaluate the relationship between the cardiac and sympathetic baroreflex sensitivities within healthy, young humans. The sensitivities of the cardiac and sympathetic baroreflexes were compared in 53 normotensive individuals (28 men and 25 women; age: 24.0 ± 0.9 years; body mass index: 24.0 ± 0.3 cm/kg2, mean ± SEM). Heart rate, arterial blood pressure, and peroneal muscle sympathetic nerve activity were recorded under resting conditions (heart rate: 58 ± 1 bpm; systolic blood pressure: 126 ± 2 mm Hg; diastolic blood pressure: 72 ± 1 mm Hg; mean arterial blood pressure: 89 ± 1 mm Hg; muscle sympathetic nerve activity: 18 ± 1 bursts per min) and during rapid changes in blood pressure induced by sequential boluses of nitroprusside and phenylephrine. Cardiac and sympathetic baroreflex sensitivities were analyzed using the slopes of the linear portions of the muscle sympathetic nerve activity-diastolic blood pressure and R-R interval-systolic blood pressure relationships, respectively. When individual cardiac baroreflex sensitivity was compared with sympathetic baroreflex sensitivity, no correlation (R-R interval: r = -0.13; heart rate: r = 0.21) was observed when studied as a group. Analysis by sex unveiled a correlation in women between the cardiac and sympathetic baroreflex sensitivities (R-R interval: r = -0.54; P = 0.01; no correlation with hazard ratio: r = 0.29). No relationship was found in men (R-R interval: r = 0.17; heart rate: r = 0.12). These results indicate that, although both cardiac and sympathetic efferents function in baroreflex control of arterial pressure, there is no correlation in their sensitivities within healthy normotensive humans. However, sex-stratified data indicate that sex-based differential correlations might exist.     

Myocardial infarction and baroreflex sensitivity. Clinical studies.

Based on solid experimental evidence the concept has emerged that analysis of autonomic reflexes, and specifically of baroreceptive reflexes, might contribute to the identification of high risk subgroups in the post myocardial infarction phase. Accordingly, we brought this concept to clinical fruition and have performed the first clinical study to investigate the potential prognostic value of baroreflex sensitivity. The present article reviews those clinical results which indicate an almost 15 times greater risk for cardiac mortality among the patients with depressed baroreflex sensitivity. Baroreflex sensitivity has also been correlated with heart rate variability and it was found that the degree of correlation is relatively weak and such that it is not possible to predict one measure from the other. Thus, these two autonomic markers are not redundant. Among the various possibilities to induce favorable alterations in the autonomic balance, our group has selected and analyzed exercise training and the chronic administration of beta-blocking agents. Exercise training, examined in a case-control study involving 70 patients, was found to increase baroreflex sensitivity by 30%. Beta-blockers were found to augment baroreflex sensitivity in 40% of the patients tested. As a logical evolution of these studies we have initiated a large prospective collaborative study destined to enroll 1200 post myocardial infarction patients and to assess the prognostic value of baroreflex sensitivity, of heart rate variability, and of traditional markers such as left ventricular ejection fraction and late potentials.     

Analgosedation-enhanced baroreflex sensitivity in acute local myocardial ischaemia.

In acute local myocardial ischaemia produced in mongrel dogs, the sensitivity of baroreflex decreased as electrical instability (vulnerability) of cardiac ventricles increased. Simultaneous administration of a benzodiazepine and a powerful analgesic (analgosedation) augmented both baroreflex sensitivity and ventricular fibrillation threshold. Modulation of neurovegetative activation of the heart by drugs in the early stage of ischaemia holds promise as a potential technique of sudden coronary death prevention.     

Analgosedation raises baroreflex sensitivity in acute myocardial ischaemia.

Acute local myocardial ischaemia is associated with a decrease in baroreflex sensitivity while electrical instability (vulnerability) of ventricles increases. Co-administration of a benzodiazepine and a potent analgesic (analgosedation) has been found to raise both baroreflex sensitivity and ventricular fibrillation threshold. Pharmacological modulation of neurovegetative ionization of the heart in the early phase of ischaemia is a promising method for preventing sudden coronary death.