Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia

OBJECTIVES: The goal of this study was to investigate the relation between serum cholesterol, arterial stiffness and central blood pressure. BACKGROUND: Arterial stiffness and pulse pressure are important determinants of cardiovascular risk. However, the effect of hypercholesterolemia on arterial stiffness is controversial, and central pulse pressure has not been previously investigated. METHODS: Pressure waveforms were recorded from the radial artery in 68 subjects with hypercholesterolemia and 68 controls, and corresponding central waveforms were generated using pulse wave analysis. Central pressure, augmentation index (AIx) (a measure of systemic stiffness) and aortic pulse wave velocity were determined. RESULTS: There was no significant difference in peripheral blood pressure between the two groups, but central pulse pressure was significantly higher in the group with hypercholesterolemia (37 +/- 11 mm Hg vs. 33 +/- 10 mm Hg [means +/- SD]; p = 0.028). Augmentation index was also significantly higher in the patients with hypercholesterolemia group (24.8 +/- 11.3% vs. 15.6 +/- 12.1%; p < 0.001), as was the estimated aortic pulse wave velocity. In a multiple regression model, age, short stature, peripheral mean arterial pressure, smoking and low-density lipoprotein cholesterol correlated positively with AIx, and there was an inverse correlation with heart rate and male gender. CONCLUSIONS: Patients with hypercholesterolemia have a higher central pulse pressure and stiffer blood vessels than matched controls, despite similar peripheral blood pressures. These hemodynamic changes may contribute to the increased risk of cardiovascular disease associated with hypercholesterolemia, and assessment may improve risk stratification.     

Central pressure: variability and impact of cardiovascular risk factors: the Anglo-Cardiff Collaborative Trial II

Pulse pressure varies throughout the arterial tree, resulting in a gradient between central and peripheral pressure. Factors such as age, heart rate, and height influence this gradient. However, the relative impact of cardiovascular risk factors and atheromatous disease on central pressure and the normal variation in central pressure in healthy individuals are unclear. Seated peripheral (brachial) and central (aortic) blood pressures were assessed, and the ratio between aortic and brachial pulse pressure (pulse pressure ratio, ie, 1/amplification) was calculated in healthy individuals, diabetic subjects, patients with cardiovascular disease, and in individuals with only 1 of the following: hypertension, hypercholesterolemia, or smoking. The age range was 18 to 101 years, and data from 10 613 individuals were analyzed. Compared with healthy individuals, pulse pressure ratio was significantly increased (ie, central systolic pressure was relatively higher) in individuals with risk factors or disease (P<0.01 for all of the comparisons). Although aging was associated with an increased pulse pressure ratio, there was still an average+/-SD difference between brachial and aortic systolic pressure of 11+/-4 and 8+/-3 mm Hg for men and women aged >80 years, respectively. Finally, stratifying individuals by brachial pressure revealed considerable overlap in aortic pressure, such that >70% of individuals with high-normal brachial pressure had similar aortic pressures as those with stage 1 hypertension. These data demonstrate that cardiovascular risk factors affect the pulse pressure ratio, and that central pressure cannot be reliably inferred from peripheral pressure. However, assessment of central pressure may improve the identification and management of patients with elevated cardiovascular risk.     

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats

Chemical stimulation of brain cholinergic neurons in many species can produce hypertension. Recent studies in this laboratory have demonstrated that clonidine inhibits this central cholinergic pressor response by inhibiting the biosynthesis of brain acetylcholine. This study was designed to determine whether methyldopa, like clonidine, could inhibit brain cholinergic neurons involved in cardiovascular regulation in freely-moving spontaneously hypertensive rats (SHR). Intravenous (i.v.) injection of methyldopa (50-200 mg/kg) produced a dose-related fall in blood pressure (29/15-54/33 mm Hg) in SHR. Intracerebroventricular (i.c.v.) injection of hemicholinium-3 (HC-3) in SHR evoked a fall in arterial pressure through inhibition of acetylcholine synthesis. Doses of HC-3 (10 micrograms, or 15 micrograms, i.c.v.) and methyldopa (50 mg/kg, i.v.) were administered to produce small reductions in arterial pressure in SHR (7-14 mm Hg diastolic, respectively). When the two agents were injected simultaneously, however, a greater than additive response was obtained (p less than 0.05). Central injection of echothiophate (a long-acting cholinesterase inhibitor) to potentiate brain cholinergic activity resulted in a sustained hypertensive response (greater than 40 mm Hg) in SHR for at least 150 minutes. Simultaneous injection of or pretreatment with methyldopa (100 mg/kg, i.v.) inhibited the pressor response to echothiophate over a time course similar to its antihypertensive response in untreated SHR. Methyldopa, however, was completely ineffective in altering the hypertensive response to central injection of carbachol (1 microgram, i.c.v.). This difference in methyldopa susceptibility between the indirect-acting (echothiophate) and direct-acting (carbachol) cholinergic agonists may be related to an inhibiting effect of methyldopa on brain acetylcholine release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulse pressure and mortality in older people

BACKGROUND: In older people, observational data are unclear concerning the relationships of systolic and diastolic blood pressure with cardiovascular and total mortality. We examined which combinations of systolic, diastolic, pulse, and mean arterial pressure best predict total and cardiovascular mortality in older adults. METHODS: In 1981, the National Institute on Aging initiated its population-based Established Populations for Epidemiologic Studies of the Elderly in 3 communities. At baseline, 9431 participants, aged 65 to 102 years, had blood pressure measurements, along with measures of medical history, use of medications, disability, and physical function. During an average follow-up of 10. 6 years among survivors, 4528 participants died, 2304 of cardiovascular causes. RESULTS: In age- and sex-adjusted survival analyses, the lowest overall death rate occurred among those with systolic pressure less than 130 mm Hg and diastolic pressure 80 to 89 mm Hg; relative to this group, the highest death rate occurred in those with systolic pressure of 160 mm Hg or more and diastolic pressure less than 70 mm Hg (relative risk, 1.90; 95% confidence interval, 1.47-2.46). Both low diastolic pressure and elevated systolic pressure independently predicted increases in cardiovascular (P<.001) and total (P<.001) mortality. Pulse pressure correlated strongly with systolic pressure (R = 0.82) but was a slightly stronger predictor of both cardiovascular and total mortality. In a model containing pulse pressure and other potentially confounding variables, diastolic pressure (P =.88) and mean arterial pressure (P =.11) had no significant association with mortality. CONCLUSIONS: Pulse pressure appears to be the best single measure of blood pressure in predicting mortality in older people and helps explain apparently discrepant results for low diastolic blood pressure.     

Peripheral augmentation index defines the relationship between central and peripheral pulse pressure

Peripheral systolic blood pressure is amplified above central aortic systolic pressure, but the late systolic shoulder of the peripheral pulse may approximate central systolic pressure. Because late systolic pressure also determines the peripheral augmentation index, a measure of pressure wave reflection within the systemic circulation, this implies a direct relationship between amplification and augmentation. We compared the late systolic shoulder of the peripheral pressure waveform with estimates of central systolic pressure obtained using a transfer function in 391 subjects undergoing diagnostic coronary angiography and/or elective angioplasty (30% with insignificant coronary artery disease). In a subset (n=12) we compared the late systolic shoulder of the peripheral pulse with central pressure obtained with a catheter placed in the aortic root. Measurements were made at baseline, during atrial pacing, and during administration of nitroglycerin. Late systolic shoulder pressure closely approximated transfer function estimates of central pressure (R=0.96; P<0.0001; mean difference+/-SD: 0.5+/-5.2 mm Hg). Despite changes in waveform morphology induced by pacing and nitroglycerin (reducing mean values+/-SE of the augmentation index from 76+/-3.8% to 66+/-4.6% and 60+/-3.3%, respectively), there was close agreement between the late systolic shoulder of the peripheral pulse and measured values of central pressure (R=0.96; P<0.001; mean difference: 1.7+/-4.8 mm Hg). In conclusion, the late systolic shoulder of the peripheral pulse closely approximates central systolic pressure and peripheral augmentation index, the ratio of central:peripheral pulse pressure. Interventions to lower augmentation index and peripheral vascular resistance will have multiplicative effects in lowering central blood pressure.     

Association between pulse pressure and C-reactive protein among apparently healthy US adults

Elevated pulse pressure has been associated with an increased risk of cardiovascular disease, which is increasingly being seen as an inflammatory disease. Thus, the mechanism underlying the link between elevated pulse pressure and cardiovascular disease risk may be inflammation. However, investigators have not examined the relationship between pulse pressure and C-reactive protein, an inflammation marker that has been closely linked to cardiovascular risk. We examined the cross-sectional relationship between pulse pressure and C-reactive protein among 9867 healthy persons 17 years of age or older who participated in the Third National Health and Nutrition Examination Survey. The association between pulse pressure and the odds of having an elevated C-reactive protein level (> or = 0.66 mg/dL) was assessed by logistic regression. In a model that adjusted for systolic blood pressure, demographic factors, cholesterol, measures of obesity, smoking, alcohol consumption, physical activity, and antihypertensive medication use, a 10 mm Hg increase in pulse pressure was associated with a 15% increase in the odds of having an elevated C-reactive protein level (odds ratio, 1.15; 95% confidence interval, 1.01 to 1.31; P=0.04). When the same model was re-run adjusting for diastolic blood pressure instead of systolic blood pressure, a 10 mm Hg rise in pulse pressure was associated with a significant 12% increase in the odds of having an elevated C-reactive protein level. Systolic and diastolic blood pressure were unrelated to C-reactive protein once pulse pressure had been accounted for. Our results suggest that increases in pulse pressure are associated with elevated C-reactive protein levels among apparently healthy US adults, independent of systolic and diastolic blood pressure.     

Cerebral microangiopathy in treatment-resistant hypertension

Cerebral microangiopathy is a cause of cognitive impairment and indicates high risk for clinically overt cerebrovascular disease. It develops in patients with or without hypertension, and different pathologies may play a supporting role. In this pilot study, the authors aimed to elucidate risk factors contributing to the deleterious action of hypertension on cerebral small vessels. A cross-sectional study in 42 patients with treatment-resistant hypertension was performed. Microangiopathy was investigated by cerebral magnetic resonance imaging (MRI). Determinants were identified by clinical investigation, computed tomography, intima-media thickness and pulse wave velocity measurement, and urinary albumin excretion. Nineteen of 42 patients had cerebral microangiopathy (23 controls). Patients were different with respect to heart rate (60.5 ± 10.2 vs 69.7 ± 15.1 beats per minute; P = .029) and systolic blood pressure during nighttime (138 ± 13 mm Hg vs 126 ± 18 mm Hg; P = .019). In addition, there were significant differences in pulse wave velocity (10.7 ± 2.0 m/s vs 9.4 ± 1.4 m/s; P = .034), peripheral pulse pressure (70.8 ± 16.3 mm Hg vs 59.2 ± 13.6 mm Hg; P = .016), central pulse pressure (62.9 ± 15.8 mm Hg vs 50.3 ± 14.2 mm Hg; P = .012), and aortic augmentation pressure (15.9 ± 6.0 vs 11.8 ± 6.6; P = .040). Systolic blood pressure and signs of hypertensive vasculopathy such as peripheral and central pulse pressure and pulse wave velocity were associated with cerebral microangiopathy in patients with long-standing treatment-resistant hypertension.     

Ambulatory pulse pressure aspredictor of outcome in older patients with systolic hypertension

We enrolled 808 older patients with isolated systolic hypertension (160 to 219/71 <95 mm Hg) to investigate whether ambulatory measurement of pulse pressure and mean pressure can refine risk stratification. The patients (≥60 years) were randomized to nitrendipine (10 to 40 mg/day) with the possible addition of enalapril (5 to 20 mg/day) or hydrochlorothiazide (12.5 to 25 mg/day) or to matching placebos. At baseline, pulse pressure and mean pressure were determined from six conventional blood pressure (BP) readings and from 24-h ambulatory recordings. With adjustment for significant covariables, we computed mutually adjusted relative hazard rates associated with 10 mm Hg increases in pulse pressure or mean pressure. In the placebo group, the 24-h and nighttime pulse pressures consistently predicted total and cardiovascular mortality, all cardiovascular events, stroke, and cardiac events. Daytime pulse pressure predicted cardiovascular mortality, all cardiovascular end points, and stroke. The hazard rates for 10 mm Hg increases in pulse pressure ranged from 1.25 to 1.68. Conventionally measured pulse pressure predicted only cardiovascular mortality with a hazard rate of 1.35. In the active treatment group compared with the placebo patients, the relation between outcome and ambulatory pulse pressure was attenuated to a nonsignificant level. Mean pressure determined from ambulatory or conventional BP measurements was not associated with poorer prognosis. In conclusion, in older patients with isolated systolic hypertension higher pulse pressure estimated by 24-h ambulatory monitoring was a better predictor of adverse outcomes than conventional pulse pressure, whereas conventional and ambulatory mean pressures were not correlated with a worse outcome.     

Favourable effects on arterial wave reflection and pulse pressure amplification of adding angiotensin II receptor blockade in resistant hypertension

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors have beneficial effects on arterial compliance and distensibility and favourably modify the arterial pressure waveform in hypertensive patients. The objective of our study was to explore the possible effects of adding an ATII AT1 receptor antagonist to an ACE inhibitor on augmentation pressure, a measure of arterial stiffness, and pulse pressure amplification in patients with poorly controlled essential hypertension. DESIGN AND METHODS: We studied a group of 18 patients with poorly controlled hypertension, despite at least three antihypertensive drugs including an ACE inhibitor, before, at 2 h and 2 weeks following the administration of 80 mg of valsartan, an ATII AT1 receptor antagonist. Haemodynamic responses were measured by cuff sphygmomanometry, arterial pulse-wave analysis and the pulse pressure gradient was calculated as the difference between the brachial pulse pressure (cuff sphygmomanometry) and derived aortic pulse pressure (arterial pulse wave analysis). RESULTS: Blood pressure decreased significantly (P<0.001) and the effect was more pronounced on central (aortic) pulse pressure than peripheral (brachial) pulse pressure. The pulse pressure amplification increased significantly (from 8+/-3 at baseline vs 12+/-7 at 2 h to 14+/-5 mm Hg at 2 weeks, P<0.01) and the augmentation pressure decreased from a baseline value of 21+/-8 to 11+/-7 at 2 h and 10+/-5 at 2 weeks, (P<0.01) following valsartan. CONCLUSION: The results of our study show that in a group of poorly controlled hypertensives, combining an ATII AT1 receptor blocker to an ACE inhibitor induced a significant fall in blood pressure. The decrease in blood pressure was accompanied by a decrease in augmentation pressure in the ascending aorta with a greater decrease in the central pulse pressure than in the peripheral, favourably increasing pulse pressure amplification between central and peripheral arteries. This effect on arterial stiffness and amplification suggests that combined angiotensin II blockade by adding an AT1 receptor blocker to an ACE inhibitor may have more beneficial effects on the blood pressure curve than simple blood pressure reduction.     

Assessment of Global Risk: A Foundation for a New, Better Definition of Hypertension

The prevalence of individuals with increased blood pressure (BP) is growing. A greater understanding of the various pathogenetic mechanisms of hypertension and associated BP increases would provide a better strategy for preventing and treating this condition. Hypertension is strongly associated with other cardiovascular risk factors. Additionally, there is no threshold of BP >115/70 mm Hg that identifies cardiovascular risk (i.e., risk is linear and doubles for each 20/10-mm Hg BP rise). These insights have led a group of hypertension experts to propose a new definition of hypertension as "a progressive cardiovascular syndrome arising from complex and interrelated etiologies," which features early markers that are "often present before blood pressure elevation is sustained." Early cardiovascular markers include widened pulse pressure, left ventricular hypertrophy, increased arterial stiffness, endothelial dysfunction, and microalbuminuria. Importantly, antihypertensive treatment for patients with prehypertension (systolic BP of 120–139 mm Hg or diastolic BP of 80–89 mm Hg) has recently been shown to prevent the development of frank hypertension. This revision of the definition of hypertension and the need to assess BP levels in the context of global cardiovascular risk should lead to earlier detection of at-risk patients.     

Epidemiology of Hypertension in the Elderly

In Western populations, mean systolic and diastolic blood pressures rise with advancing age up to the sixth decade of life, whereupon systolic blood pressure continues to increase and diastolic pressure starts to decline. The ensuing widening of pulse pressure is mainly ascribed to stiffening of the arterial vasculature. When hypertension is defined as systolic blood pressure of at least 140 mm Hg and/or diastolic pressure of at least 90 mm Hg, its prevalence amounts to 60%–70% of the population above 60 years of age. About 60% of these hypertensives have isolated systolic hypertension—that is, elevated systolic pressure and normal diastolic pressure. It should be realized, however, that approximately 25% of those labeled hypertensive on the basis of conventional blood pressure measurements have normal blood pressure on ambulatory blood pressure monitoring, or so-called white-coat, isolated clinic, or nonsustained hypertension. There is little doubt that elevated blood pressure leads to a number of cardiovascular complications. Whereas diastolic blood pressure has been emphasized for many years, the paradigm has shifted toward systolic blood pressure. In addition, pulse pressure has been shown to be an important predictor of cardiovascular events and death, above and beyond the predictive power of mean blood pressure.     

The local component of the acute cardiovascular response to simulated apneas in brain-dead humans

STUDY OBJECTIVES: To investigate the local cardiovascular response to hypoxemia and hypercapnia in a simulated central apnea model in which the central autonomic regulation was absent. DESIGN: Experimental study. SETTING: A university hospital. INTERVENTIONS: A simulated central apnea model achieved by a particular setting of the mechanical ventilator in 10 brain-dead patients. MEASUREMENTS: Hemodynamic studies using right-heart catheterization and continuous monitoring of arterial blood gas levels. RESULTS: Hypercapnic hypoxic apneas were associated with no change in heart rate, fall in mean systemic arterial pressure and systemic vascular resistance (from 83 +/- 9 to 68 +/- 7 mm Hg and 1,115 +/- 82 to 768 +/- 58 dyne.s.cm(-5), respectively; each p < 0.05), and rise in mean pulmonary artery pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure (PCWP) [from 17 +/- 1.5 to 26 +/- 3 mm Hg, 102 +/- 27 to 166 +/- 43 dyne.s.cm(-5), and 10 +/- 1 to 14 +/- 2 mm Hg, respectively; each p < 0.05]. CONCLUSION: Our results suggest that in the absence of central autonomic regulation in humans, apnea-induced hypoxemia and/or hypercapnia are associated with peripheral vasodilatation and pulmonary vasoconstriction, which are probably local in origin, as well as a significant increase in PCWP indicating cardiac dysfunction.     

Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation

The neurotransmitter acetylcholine is considered essential for proper functioning of the hippocampus-dependent declarative memory system, and it represents a major neuropharmacological target for the treatment of memory deficits, such as those in Alzheimer's disease. During slow-wave sleep (SWS), however, declarative memory consolidation is particularly strong, while acetylcholine levels in the hippocampus drop to a minimum. Observations in rats led to the hypothesis that the low cholinergic tone during SWS is necessary for the replay of new memories in the hippocampus and their long-term storage in neocortical networks. However, this low tone should not affect nondeclarative memory systems. In this study, increasing central nervous cholinergic activation during SWS-rich sleep by posttrial infusion of 0.75 mg of the cholinesterase inhibitor physostigmine completely blocked SWS-related consolidation of declarative memories for word pairs in human subjects. The treatment did not interfere with consolidation of a nondeclarative mirror tracing task. Also, physostigmine did not alter memory consolidation during waking, when the endogenous central nervous cholinergic tone is maximal. These findings are in line with predictions that a low cholinergic tone during SWS is essential for declarative memory consolidation.     

浙江景宁人群中α-内收蛋白基因Gly460Trp多态性与外周及中心动脉血压的关系

目的探讨在中国畲族人群中α-内收蛋白基因Gly460Trp多态性与外周及中心动脉血压的关系。方法在浙江省景宁县随机选择6个村,以核心家系为单位募集人群样本,运用水银柱血压计听诊法连续测量坐位非优势臂血压5次,取平均值用做统计分析。运用标准化问卷收集饮酒、吸烟、高血压用药史。采用SphygmoCor动脉脉搏波分析仪测量中心动脉血压。采集静脉血,分离DNA,以限制性酶切长度多态性方法检测α-内收蛋白基因的基因型。使用方差分析、广义估计方程(generalizedestimatingequations,GEE)进行关联分析。结果442例受检者中包括230例(52·0%)女性,116例(26·2%)高血压患者,其中49例(11·1%)服用抗高血压药物。α-内收蛋白GlyGly、GlyTrp、TrpTrp三个基因型的频率分别为21·3%、54·5%和24·2%。α-内收蛋白Gly460Trp多态性与肱动脉收缩压、舒张压及脉压无显著性关联,但在调整性别、年龄、年龄2、体重指数、有无吸烟、饮酒、抗高血压药物治疗等协变量前后,该多态性与中心动脉收缩压及中心脉压均有显著相关性(P<0·02)。GlyGly、GlyTrp、TrpTrp三个基因型的中心动脉收缩压分别为(122·5±3·5)mmHg、(114·1±1·5)mmHg、(109·1±1·8)mmHg(P=0·01)。相应的中心脉压值分别为(39·4±1·3)mmHg、(36·4±1·0)mmHg、(32·9±0·9)mmHg(P=0·002)。结论在浙江景宁畲族人群中,α-内收蛋白基因Gly460Trp多态性与中心动脉的收缩压及脉压有显著相关性,Trp等位基因可能对中心动脉血压增高有保护作用。     

Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial

Pulse pressure has been more strongly associated with cardiovascular outcomes, especially myocardial infarction and heart failure, than has systolic, diastolic, or mean arterial pressure in a variety of populations. Little is known, however, of the comparative effects of various classes of antihypertensive agents on pulse pressure. In retrospective analyses of the Veterans Affairs Single-Drug Therapy for Hypertension Study, we compared changes in pulse pressure with 6 classes of antihypertensive agents: 1292 men with diastolic blood pressure of 95 to 109 mm Hg on placebo were randomized to receive hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo. Drug doses were titrated to achieve a goal diastolic blood pressure of <90 mm Hg during a 4- to 8-week medication titration phase. Pulse pressure change (placebo subtracted) was assessed from baseline to the end of the 3-month titration and 1-year maintenance. Mean baseline systolic, diastolic, and pulse pressures were 152, 99, and 53 mm Hg, respectively. Reductions in pulse pressure during titration were greater (P<0.001) with clonidine (6.7 mm Hg) and hydrochlorothiazide (6.2 mm Hg) than with captopril (2.5 mm Hg), diltiazem (1.6 mm Hg), and atenolol (1.4 mm Hg); reduction with prazosin (3.9 mm Hg) was similar to all but clonidine. After 1 year, pulse pressure was reduced significantly more (P<0.001) with hydrochlorothiazide (8.6 mm Hg) than with captopril and atenolol (4.1 mm Hg with both); clonidine (6.3 mm Hg), diltiazem (5.5 mm Hg), and prazosin (5.0 mm Hg) were intermediate. These data show that classes of antihypertensive agents differ in their ability to reduce pulse pressure. Whether these differences affect rates of cardiovascular events remains to be determined.     

Reference values for the arterial pulse wave in Chinese

BACKGROUND: Pulse wave analysis using the SphygmoCor system allows the estimation of central pulse pressure (PP) and peripheral and central augmentation indexes (AIxs). We studied the limits of normality of these measurements in Chinese. METHODS: We computed limits of normality as the 95% confidence boundaries from regression models relating the arterial indexes to age. RESULTS: The reference population included 924 subjects (50.7% men, mean age 40.7 years) without overt cardiovascular disease. Men, compared to women, had higher peripheral (43.3 vs. 41.7 mm Hg; P = 0.01) and central (32.9 vs. 30.9 mm Hg; P < 0.0001) PPs, but lower peripheral (69.0 vs. 74.2%; P < 0.0001) and central (16.6 vs. 21.0%; P < 0.0001) AIxs. All arterial measurements showed a curvilinear relation with age. Both before and after adjustment for confounding factors, peripheral and central PPs increased less (P < or = 0.01) with age in men than in women, whereas the relation of peripheral and central AIxs with age was similar (P > or = 0.13) in both sexes. In 40-year-old Chinese, approximate thresholds for peripheral and central PPs, peripheral and central AIxs were 58 mm Hg, 48 mm Hg, 105% and 45%, respectively. Considering the age range from 20 to 60 years, thresholds varied within approximately 5 mm Hg, approximately 10 mm Hg, approximately 20%, and approximately 15% of the aforementioned thresholds for peripheral and central PPs, peripheral and central AIxs, respectively. CONCLUSIONS: Pending further validation in prospective studies, our present study provides preliminary diagnostic thresholds for PP and AIxs in Chinese.     

Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans

OBJECTIVES: We sought to investigate baroreceptor regulation of sympathetic nerve activity and hemodynamics after inhibition of nitric oxide (NO) synthesis. BACKGROUND: Both the sympathetic nervous system and endothelium-derived substances play essential roles in cardiovascular homeostasis and diseases. Little is known about their interactions. METHODS: In healthy volunteers, we recorded muscle sympathetic nerve activity (MSA) with microneurography and central hemodynamics measured at different levels of central venous pressure induced by lower body negative pressure. RESULTS: After administration of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min), systolic blood pressure increased by 24 mm Hg (p = 0.01) and diastolic blood pressure by 12 mm Hg (p = 0.009), while stroke volume index (measured by thermodilution) fell from 53 to 38 mL/min/m2 (p < 0.002). Administration of L-NMMA prevented the compensatory increase of heart rate, but not MSA, to orthostatic stress. The altered response of heart rate was not due to higher blood pressure, because heart rate responses were not altered during infusion of the alpha-1-adrenoceptor agonist phenylephrine (titrated to an equal increase of systolic blood pressure). In the presence of equal systolic blood pressure and central venous pressure, we found no difference in MSA during phenylephrine and L-NMMA infusion. CONCLUSIONS: This study demonstrates a highly specific alteration of baroreceptor regulation of heart rate but not muscle sympathetic activity after inhibition of NO synthesis in healthy volunteers. This suggests an important role of NO in reflex-mediated heart rate regulation in humans.     

Rapid neurosecretory and cardiovascular response to osmotic stimulation in conscious mice

Experiments were performed to evaluate the neuroendocrine and cardiovascular effects of osmotic stimulation in mice. Hypertonic saline (HS) was administered centrally or via the blood stream to conscious mice during measurement of blood pressure (BP), heart rate (HR) and plasma vasopressin (VP) and oxytocin (OT). A test of hypovolemia on VP secretion was also performed. Chronic carotid arterial cannulas were inserted for blood sampling, cardiovascular monitoring and vascular injections. Intracerebroventricular (ICV) cannulas were used for central injections. Vascular injection of HS (30 microl, 3.4 M NaCl) caused rapid and transient increases in plasma VP and OT. Plasma VP increased from 5.6 +/- 0.9 to 10.0 +/- 1.0 pg/ml, while plasma OT increased from 1.5 +/- 0.6 to 8.6 +/- 2.4 pg/ml at the earliest time point, immediately after ICV injection. ICV osmotic stimulation produced a rapid and sustained increase in plasma VP, with no change in OT. Plasma VP levels were increased from basal levels of 5.1 +/- 1.5 to 13.1 +/- 4.6, 11.4 +/- 1.5, 12.6 +/- 1.7 pg/ml at 0, 1 and 5 min after injection, respectively. ICV HS also increased plasma corticosterone. BP was increased by both vascular and central osmotic stimulation. Vascular HS increased BP immediately (Delta15.3 +/- 1.7 mm Hg, 0 min) and transiently (Delta-3.9 +/- 4.6 mm Hg, 5 min) while central HS produced a sustained increase in BP (Delta10 +/- 1.4 and Delta9.8 +/- 1.9 mm Hg, 0 and 5 min). Osmotic stimulation produced no significant changes in HR. Acute hemorrhage (approximately 10% decrease in blood volume) increased plasma VP (4.9 +/- 1.0 vs. 8.4 +/- 2.2 pg/ml). These results show the pattern of endocrine and cardiovascular responses to osmotic stimulation in conscious mice. They demonstrate that (1) there are extremely rapid changes in plasma VP and OT; (2) plasma OT is increased only after peripheral vascular hypertonic injection, and (3) central and peripheral osmotic stimulations are associated with pressor responses.     

Pulse wave analysis to assess vascular compliance changes in stable renal transplant recipients

BACKGROUND: Calcineurin inhibitor drugs (cyclosporine and tacrolimus) given to renal transplant recipients to prevent rejection are associated with an increased incidence of hypertension. Reduced arterial compliance, which is a consequence of hypertension, is associated with an increased risk of cardiovascular disease and can be measured noninvasively using pulse wave analysis technology. The purpose of the study was to determine whether calcineurin inhibitor drugs have any effect on arterial compliance. METHODS: A total of 36 stable renal transplant recipients were evaluated using pulse wave analysis to determine large and small vessel compliance. Of the patients, 18 were receiving cyclosporine and 18 tacrolimus. Patients were matched for age and sex. RESULTS: No significant differences in systolic blood pressure, diastolic blood pressure, heart rate, or small vessel compliance were observed. There was a significant decrease in large vessel compliance in patients receiving tacrolimus versus those receiving cyclosporine, respectively (13.5 +/- 4.0 mL/mm Hg x 10 v 9.9 +/- 3.3 mL/mm Hg x 10; P =.005). CONCLUSIONS: Differences in large vessel compliance in renal transplant subjects may depend on the choice of calcineurin inhibitor. Specifically, decreased large vessel compliance in tacrolimus-treated subjects may be associated with an increased cardiovascular risk. This may be due to a difference in vascular collagen accumulation or to elastin loss in large elastic arteries.     

Effect of coffee and cigarette smoking on the blood pressure of untreated and diuretic-treated hypertensive patients

Patients with mild hypertension who habitually smoked cigarettes and consumed caffeine were examined after they abstained from caffeine and cigarettes overnight. Their mean blood pressure (147/89 mm Hg) was substantially lower than values recorded in the clinic (164/102 mm Hg) and remained so when they continued to abstain (149/94 mm Hg at two hours). Smoking two cigarettes (3.4 mg nicotine) elevated blood pressure by 10/8 mm Hg, but for only 15 minutes. Drinking coffee (200 mg caffeine) elevated blood pressure by up to 10/7 mm Hg between one and two hours. Combined coffee ingestion and cigarette smoking caused a sustained rise in blood pressure from 5 to 120 minutes to levels similar to those measured in the clinic (162/102 mm Hg at two hours). Similar results were obtained in thiazide-treated patients. The interaction of coffee and cigarettes on blood pressure, but not on pulse rate, was significant. The pressor effect of cigarette smoking and caffeine ingestion in combination may be important in the evaluation of patients with mild hypertension.