Evidence of early degenerative changes in large arteries in human essential hypertension

Noninvasive evaluation of brachial artery diameter (pulsed Doppler velocimetry) and pulse wave velocity (strain gauge mechanography) was performed in 23 normal subjects and 49 patients with uncomplicated essential hypertension. Pulsatile arterial function was described in terms of derived characteristic impedance and arterial compliance. Compared with normal controls, hypertensive patients had greater arterial diameter (p less than 0.01) and pulse wave velocity (p less than 0.001). Two nomograms obtained from normal subjects relating the product of age and diastolic pressure to diameter and pulse wave velocity were used for analysis of the hypertensive group; 35 patients were inside the 95% confidence limits of the diameter and pulse wave velocity nomograms (Group 1), while 14 patients were outside the pulse wave velocity nomogram (Group 2). Age and mean pressure were similar, but pulse wave velocity was higher (p less than 0.001), arterial compliance lower (p less than 0.001), and characteristic impedance higher (p less than 0.001) in Group 2 than in Group 1. The amplitude of pulse pressure was higher in Group 2 than in Group 1 (p less than 0.001), and a negative correlation was found between pulse pressure and arterial compliance in Group 2, but not in Group 1. Thus, in the majority of hypertensive patients, arterial modifications could be related to the normal influence of age and pressure. In contrast, other patients exhibited features suggesting excessive arterial stiffness, manifested by abnormally high pulse wave velocity, decreased arterial compliance, and increased characteristic impedance.     

Paradoxal diminution of resistance of the large arteries in human essential hypertension

Segmental pressure drop and longitudinal resistance of brachial artery were evaluated in 11 normotensive (NT) and 19 hypertensive (HT) subjects of similar age by measuring arterial diameter (D), blood velocity (V) and flow (Q) with pulsed Doppler and blood viscosity (mu) at 96 sec-1 with a coaxial cylinder viscometer. Mean pressure drop (delta P) per unit of length of artery was calculated according to the relation delta P = 4 tau/D, where tau is the mean wall shear stress evaluated on the basis of a Poiseuille velocity profile by the formula: r = vV/D. Brachial artery resistance per unit of length was deduced as the (delta P/Q) ratio. (table; see text) In the overall normotensive and hypertensive group, (n = 30), pressure drop (delta P) was negatively correlated with mean blood pressure (r = -0.55, P less than 0.01). Despite increased viscosity hypertensive patients have a decreased resistance of large arteries whose mechanisms include a reduction in shear stress close to the endothelium and a dilation of the conduit artery; these two abnormalities contribute to decrease the viscous force of the circulating blood column against the arterial wall.     

Vaso-dilating drugs and the large arteries in essential hypertension

Vasodilating drugs are commonly used in the treatment of hypertension. These antihypertensive agents are considered as acting on small arteries which are preferentially damaged in the hypertensive vascular disease. Recent studies have emphasized that the hemodynamic abnormalities in hypertension were not restricted to arterioles but involved also large arteries, resulting in a decrease in arterial compliance. This finding is potentially important since cardio-vascular morbidity and mortality in patients treated for hypertension is related to ischemic accidents related to alterations of large vessels, as observed in the coronary and the carotid-cerebral circulation. From this observation, it ensues that the study of the effects of vasodilating drugs on the large arteries of hypertensive patients should be extremely relevant to improve cardiovascular morbidity and mortality. On the basis of experimental studies, several cases of pharmacological dissociation in the dilatation of small and large arteries have been observed in animals, mainly in the coronary circulation. However, little research has been done on the effect of antihypertensive drugs on large arteries in men with essential hypertension. In the present review, the hemodynamic concepts and the methodologic basis for the study of large arteries in man are presented. Thereafter, the different aspect of the dilatation of small and large arteries in hypertension are analyzed, with the study of consequences on the conduit and the buffering functions of large arteries and on the development of cardiac hypertrophy. Finally, large arteries have also an important baroreflex function involved in the neuro-humoral consequences of vasodilatation. This point will be particularly described and interpreted.     

Structural abnormalities of small resistance arteries in essential hypertension

Regardless of the mechanisms that initiate the increase in blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, the small arteries smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, while in some secondary forms of hypertension, a hypertrophic remodeling may be detected. Also, in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling of subcutaneous small arteries is present. The results from our own group have suggested that indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Therefore, the regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure, both in human and in animal models of genetic and experimental hypertension. A complete normalization of small resistance artery structure is demonstrated in hypertensive patients, after long-term and effective therapy with ACE inhibitors, angiotensin II receptor blockers and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin–angiotensin system seems to be effective in this regard. In conclusion, there are several pieces of evidence that suggest that small resistance artery structure may be considered an intermediate endpoint in the evaluation of the effects of antihypertensive therapy; however, there are presently no data available about the prognostic impact of the regression of vascular structural alterations in hypertension and diabetes.     

Reduction of peripheral flow reserve impairs endothelial function in conduit arteries of patients with essential hypertension

BACKGROUND: A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit arteries. Both have been demonstrated to predict future cardiovascular events. OBJECTIVE: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. DESIGN: In 43 hypertensive patients (HT) and 38 normotensive controls (NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation (FMD), using high-resolution ultrasound. Peripheral flow reserve (FR) was determined via measurements of forearm blood flow at rest and during increments of reactive hyperaemia, using venous occlusion plethysmography. RESULTS: FMD was markedly impaired in HT (3.6 +/- 0.3%) as compared with NT (10.2 +/- 0.3%), whereas maximum brachial artery diameter following endothelium-independent dilatation was similar in both groups. In hypertensive patients FR was significantly reduced (HT, 3.2 versus NT, 6.0) during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD (r = 0.68, P < 0.01). Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD (r2 = 0.46, P < 0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60%. CONCLUSIONS: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream conduit arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension.     

Non invasive evaluation of endothelial shearing phenomena in human arteries. Application to essential hypertension

Pulsatile wall shear conditions close to the brachial artery were evaluated in 11 normotensive and in 19 hypertensive patients of similar age by determining arterial diameter and centerline blood velocity with a pulsed Doppler and blood viscosity at 96 sec-1 with a coaxial cylinder viscometer. A Womersley model of intraluminal distribution of blood velocities enabled to determine from unsteadiness parameter alpha of Womersley, arterial diameter and maximal minimal and pulse (maximal-minimal) values of centerline velocity, the maximal minimal and pulse shear rate and shear stress (product between shear rate and viscosity) close to the endothelium. Compared to normotensives hypertenvises had higher arterial diameter (p less than 0.001), lower maximal minimal and pulse centerline velocities (p less than 0.001, p less than 0.01, p less than 0.001) higher blood viscosity (p less than 0.001), lower maximal, minimal and pulse wall shear rate (p less than 0.001, p less than 0.05, p less than 0.001) and lower maximal minimal and pulse shear stress (p less than 0.01). In the overall normotensive and hypertensive group, mean blood pressure negatively correlated to maximal minimal and pulse shear rates (r = -0.65; r = -0.45, r = -0.63) and to maximal, minimal and pulse shear stress (r = -0.46; r = -0.37, r = -0.48). Thus, hypertension is associated with a reduction of oscillating shear conditions in the viscosity of the brachial artery wall which might in long term influence structural and/or functional response to the endothelium.     

Angiotensin receptor antagonist losartan improves endothelial function of epicardial coronary arteries in patients with essential hypertension

BACKGROUND: Angiotensin II can impair endothelial function, which is mediated by the angiotensin II type 1 receptor subtype. HYPOTHESIS: The study sought to determine whether treatment with the angiotensin II type 1 receptor antagonist losartan would restore the normal dilation of the left main coronary artery (LMCA) by cold pressor test in patients with essential hypertension, as shown by echocardiography. METHODS: The study population included 30 patients with mild to moderate essential hypertension and 30 matched healthy subjects. Measurements of the cold pressor test-induced and nitroglycerin-induced changes in LMCA diameter by echocardiography were performed at the end of the washout period and after 12 weeks of losartan administration. RESULTS: The percent change in LMCA diameter induced by the cold pressor test in hypertensive patients (-3.5 +/- 8.8%) was significantly lower than that in control subjects (10.2 +/- 3.7%, p<0.0001). After losartan treatment, the percent change (13.9 +/- 8.4%) was significantly higher than that before losartan treatment (-3.5 +/- 8.8%, p < 0.0001), but not significandy different between the 17 hypertensive patients with satisfactory control of blood pressure (13.8 +/- 9.1%) and the 13 hypertensive patients without satisfactory control of blood pressure (14.0 +/- 7.7%, p = 0.9). Losartan treatment in patients with essential hypertension did not modify the percent change in LMCA diameter caused by sublingual administration of nitroglycerin (23.2 +/- 14.0% vs. 27.3 +/- 13.7%, p = 0.2). CONCLUSIONS: This study demonstrates that treatment with losartan normalized response of the LMCA to the cold pressor test in patients with mild to moderate essential hypertension and that this effect is not dependent on the reduction of blood pressure.     

Heart rate affects endothelial function in essential hypertension

Increased heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in the general population and in some clinical conditions. Endothelial dysfunction is an adverse prognostic factor for cardiovascular events. The aim of the study was to evaluate the effect of HR on central hemodynamic parameters and endothelial function in hypertension. We evaluated forearm blood flow (FBF) response to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) in 30 patients with HR ≤60 min^?1 and 30 with HR ≥80 min^?1. The FBF was measured by strain-gauge plethysmography. Transesophageal atrial pacing was used to increase the HR. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and correlate hemodynamic indices. The FBF response to ACh is lower in hypertensives with HR ≤60 min^?1 than in those with HR ≥80 min^?1 (10.6 ± 4.2 vs. 13.6 ± 5.1 ml × 100 ml^?1 of tissue × min^?1, P < 0.001). Vascular resistance decreases to 9.3 ± 2.8 U in patients with lower HR versus 7.2 ± 2.1 U in those with higher HR (P = 0.002). The FBF response to SNP is similar in both groups. Central systolic and pulse pressure are higher in bradycardic patients than in those with HR ≥80 min^?1 (140 ± 8 vs. 131 ± 8 mmHg, P = 0.0001 and 49 ± 10 vs. 39 ± 11 mmHg, P = 0.0001). All central hemodynamic parameters decrease during incremental atrial pacing. Augmentation index is the strongest predictor of endothelial dysfunction at multivariate analysis. These findings demonstrate that low HR affects endothelium-dependent vasodilation in hypertension. Increased central aortic pressure and hemodynamic correlates seem to be the underlying mechanisms by which bradycardia interferes with endothelium-dependent reactivity.     

原发性高血压患者颈动脉内膜-中层厚度与冠状动脉内皮功能的关系

目的:应用超声观察原发性高血压(EH)患者颈动脉内膜-中层厚度(IMT),并探讨其冠状动脉内皮功能及两者的相关性。方法:选择60例EH患者(EH组)、30例健康体检者(正常对照组),测定其颈动脉IMT及冷加压试验前后冠状动脉左主干内径变化百分率。结果:EH患者颈动脉IMT较正常对照组增厚,冷加压试验冠状动脉左主干内径变化百分率明显低于正常对照组。颈动脉IMT与冷加压试验冠状动脉左主干内径变化呈显著负相关。结论:EH患者存在明显的颈动脉IMT增加及冠状动脉内皮功能减低。     

高血压血管内皮功能与血浆SOD、丙二醛水平的相关性研究

目的:通过检测原发性高血压患者血浆中一氧化氮(NO)、超氧化物歧化酶(SOD),丙二醛(MDA)含量,探讨高血压血管内皮功能与氧化应激相关性。方法:选取原发性高血压患者30例,无高血压健康人28例,分别用硝酸还原酶法、硫代巴比妥酸法及黄嘌呤氧化酶法检测NO、SOD、MDA含量。结果:与正常对照组相比,原发性高血压患者血浆中NO、SOD水平显著下降(P<0.05),MDA水平显著升高(P<0.05)。结论:原发性高血压病人血管内皮功能减退,NO减少,与氧化应激增强有关。     

非洛地平对高血压患者内皮功能的影响

目的　探讨高血压患者内皮血管活性物质的变化及非洛地平对其影响。方法　对 30例高血压患者和 2 4例正常对照组的血浆采用化学比色法测定 NO、NOS及采用射放免疫分析法测定 ET、Ang- 、TXA2 及 PGI2 ,并进行对照研究 ;对高血压组给予非洛地平治疗 ,并进行治疗前后的对照研究。结果　高血压组 ET、Ang- 及 TXA2 明显高于正常对照组 ,而 NO、NOS及 PGI2 明显低于正常对照组 ;非洛地平治疗组治疗后 ET、Ang- 及 TXA2 明显低于治疗前 ,NO、NOS及 PGI2 较治疗前无明显变化 ;非洛地平治疗高血压有效率 83.3%。结论　非洛地平抗高血压作用除主要通过拮抗钙通道以外 ,尚可通过降低 ET、Ang- 及 TXA2 起作用 ,而 NO通路不是其主要的作用机制。     

Effects of long-term nicardipine treatment on hemodynamics of large arteries in essential hypertension

Summary The effects of the calcium-entry blocker nicardipine on brachial hemodynamics were studied in 22 patients (18 male, 4 female) with essential hypertension, who were treated with 20 mg tid for 1 year. Compliance, characteristic impedance, vascular resistances, and tangential tension were measured before treatment and after 1, 3, and 12 months of treatment by an automatic recording from a B-mode, high-resolution, real-time scanner and pulsed Doppler velocimetry for the calculation of the flow volume. We observed statistically significant variations in compliance and impedance after 1 month (3.21±0.59 dyn^–1 cm⁴ 10^–7 vs. 1.26±0.16 dyn^–1 cm⁴ 10^–7 and 50.6±4.7 dyn s cm^–510² vs. 91.4 ±7.3 dyn s cm^–5 10², respectively; mean±SEM; p<0.001), while tangential tension was significantly reduced after only 3 months (23.2±2.2 mmHg vs. 25.4±2.3 mmHg cm; p<0.05). The correlation between variations in mean blood pressure and in the hemodynamic parameters studied remained statistically significant throughout the study. Nicardipine improved the parameters of large-artery hemodynamics that favor a normal systolic pulse.     

Effects of perindopril on elastic and structural properties of large arteries in essential hypertension

BACKGROUND: Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, is a well-recognized antihypertensive drug. Its ability to protect against cardiovascular events in hypertension has also been demonstrated. It decreases the stiffness of the larger arteries; questions remain as to the mechanisms involved and whether it is blood pressure (BP) control-dependent. OBJECTIVES: To correlate the BP response to ACE inhibition therapy with changes in arterial stiffness as evaluated by pulse wave velocity (PWV), and to correlate these changes in arterial stiffness with alterations in indicators of vascular collagen metabolism serum levels of metalloproteinase (MMP)-1 and tissue inhibitor of MMP-1 (TIMP-1). METHODS: A total of 162 patients aged 18 to 70 years with stage 1 and 2 essential hypertension (diastolic BP 95 mmHg to 114 mmHg) were enrolled to receive six months (M6) of therapy with the ACE inhibitor, perindopril. Patients were either treatment-na?ve or had not received any antihypertensive treatment for at least six months before the study. RESULTS: Mean BP was significantly reduced after two months (M2) of therapy (P=0.00001) and remained stable thereafter. In addition to the significant mean changes in PWV observed at M2 (P=0.00001), further reductions in PWV were noted at M6 (P=0.007). The change in PWV between baseline (M0) and M2 was significantly correlated to all BP parameters at M0 (correlation coefficient at M2 was 0.189 or greater). However, no correlation was seen regarding BP parameters at M2 and further M2 to M6 changes in PWV, suggesting a decrease of arterial stiffness independent of BP reduction. The expression of TIMP-1 and MMP-1 was highly variable and demonstrated no correlation with BP or PWV. CONCLUSIONS: Reductions in BP and PWV appear to be correlated during the first two months of perindopril therapy. After six months, PWV continues to decrease independently of any further reduction in BP, suggesting the occurrence of a pressure-independent pharmacological remodelling of the arterial wall. A long-term, double-blind, randomized trial could be required to confirm that the observed increase in vascular distensibility induced by perindopril is related to a mechanism of action other than a reduction in BP.     

Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo

We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension (200 mm Hg for 10 seconds to 15 minutes). In open-chest anesthetized dogs, the left anterior descending coronary artery was perfused at constant pressure. Coronary diameter (D) was measured with piezoelectric crystals. At a control perfusion pressure of 80 mm Hg, serotonin produced dose-dependent constriction of the large coronary artery (mean +/- SEM; delta D = -22 +/- 10 microns at 5 micrograms/min; -108 +/- 50 microns at 50 micrograms/min). Increasing perfusion pressure to 200 mm Hg increased flow 515 +/- 79% and coronary diameter 509 +/- 9 microns. After 15 minutes of hypertension, when coronary diameter had returned to baseline values, the constriction of the large artery to serotonin was potentiated (delta D = -89 +/- 33 microns at 5 micrograms/min; -207 +/- 45 microns at 50 micrograms/min; p less than 0.05). Hypertension for 1-5 minutes potentiated constrictor responses of large coronary arteries for at least 2 1/2 hours. Removal of endothelium prevented effects of hypertension on constrictor responses of large arteries to serotonin. Hypertension did not alter constrictor responses to angiotension II (1 and 2.5 micrograms/min) or methoxamine (50 and 100 micrograms/min) or the dilator response to acetylcholine (40 micrograms/min). Acute hypertension altered endothelial morphology. There were small endothelial craters following 10 seconds of hypertension, and disruption of endothelial junctions with leukocyte adherence following 1-15 minutes of hypertension. We conclude that acute hypertension alters constrictor responses of large coronary arteries to serotonin by impairing endothelial function and not by directly affecting vascular smooth muscle. These effects of acute hypertension on vascular reactivity are selective in that they do not involve non-endothelium-dependent agents or the endothelium-dependent agent, acetylcholine. The effect of hypertension also persists long after pressure is restored to normotensive levels.     

高血压患者内皮功能与左心室肥厚的关系及左旋氨氯地平的干预作用△

目的研究轻、中度原发性高血压（高血压）患者内皮功能与左心室肥厚的关系以及左旋氨氯地平对其的干预作用,方法测定62例新发和（或）未经治疗的轻、中度高血压患者的收缩压、舒张压、心率和血清肌酐、丙氨酸氨基转移酶、三酰甘油、总月口固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、高敏C反应蛋白、空腹血糖和2h血糖以及一氧化氮、内皮素-1浓度;同时测定超声心动网指标并计算左心室质量指数。根据左心率质赶指数分为左心室肥厚组（30例）和非肥厚组（32例）,同时选择同期健康体检的27名正常者作为对照组。高血压患者均给了左旋氨氯地平2．5lng／d治疗,随访1年。高血乐组各观察指标治疗8周及1年后测量并与治疗前进行比较。结果（1）高血压组血清三酰甘油、总胆同醇、低密度脂蛋白胆固醇、高敏C反应蛋白和内皮素-1浓度均显著高丁对照组,一氧化氮则显著低于对照组,差异有统计学意义（P〈0．05）。（2）治疗8周后．高血压组收缩压、舒张乐及血清总胆同醇、低密度脂蛋白胆同醇、高敏C反应蛋白、内皮素-1浓度均较治疗前显著降低。一氧化氮浓度升高,差异具有统计学意义（P〈0．05）。（3）左心室肥厚组血清内皮索-l浓度显著高于非肥厚组．一氧化氮浓度显著低于非肥厚组,差异具有统计学意义（P〈0．05）。（4）Pearson相关分析结果：高血压患者血清一氧化氮浓度与室间隔厚度（r=-0．258,P〈0．05）及左心室质量指数（r=-0．301,P〈0．05）负相关;叭清内皮素-1浓度与左心窜后擘厚度（r=0．253,P〈0．05）呈正相天。（5）治疗1年后,高血压组舒张及收缩功能与治疗前比较,差异无统计学意义（P〉0．05）,左心室质量指数明显下降,差异有统计学意义（P〈0．05）。结论高血乐患者存存内皮功能受损,左心室肥厚患者更为严重,其内皮功能与左心室肥厚具有相关性。左旋氦氯地平呵以改善血管内皮功能和逆转左心室肥厚,     

高血压病患者脂餐后血管内皮功能受损

目的探讨高血压病患者高脂餐后血管内皮功能变化.方法 20例高血压病患者和20名正常对照者在禁食12 h后接受高脂餐负荷试验.分别测定餐前及餐后2、4、5、7 h血清血脂浓度.采用高分辨血管外超声法检测餐前及餐后4 h肱动脉血流介导的内皮依赖性血管舒张功能.结果两组受试者的空腹血脂水平无显著差异;餐后2、4、5 h血清甘油三酯(TG)浓度较空腹状态有显著升高.但高血压病组具有较高的餐后4、5、7 h血清TG浓度及其净增加值.两组受试者餐后内皮依赖性血管舒张功能均较空腹时显著受损.高血压病组,(5.38±1.95)% vs(2.21±1.06)%;对照组,(9.38±2.42)% vs(6.25±2.23)%;P<0.001.高血压病组的空腹以及餐后内皮依赖性血管舒张功能较对照组均显著受损(P<0.001),且餐后内皮依赖性血管舒张功能的受损程度显著高于对照组[(58±14)% vs (33±17)%,P<0.001].相关分析显示餐后4 h 血清TG浓度净增加值与餐后内皮依赖性血管舒张功能的变化率显著正相关(r=0.373,P<0.05).结论高血压病患者餐后显著而持久的高甘油三酯血症可导致餐后内皮依赖性血管舒张功能严重损害.     

Treatment with irbesartan or atenolol improves endothelial function in essential hypertension

OBJECTIVES: To investigate if antihypertensive treatment could improve endothelium-dependent vasodilatation in hypertensive patients, and whether the angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1-receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS: Thirty-four patients (28 men and six women) with mild-to-moderate essential hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily 150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous occlusion plethysmography during local intra-arterial infusions of methacholine and sodium nitroprusside, to evaluate endothelium-dependent and endothelium-independent vasodilatation, respectively. Measurements of FBF were undertaken at the end of the run-in placebo period and repeated after 3 months of active antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4 microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no difference between the two study drugs. No significant changes in endothelium-independent vasodilatation were induced by irbesartan or by atenolol. CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.     

Flow-mediated vasodilation and distensibility in relation to intima-media thickness of large arteries in mild essential hypertension

Whether endothelial dysfunction in essential hypertension is a cause or a consequence of structural vessel wall alterations is not known. The purpose of the present study was to compare flow-mediated vasodilation and mechanical vessel wall properties of large arteries between never treated mild essential hypertensive patients with normal intima-media thickness (IMT) and those exhibiting intima-media thickening. We measured brachial and carotid artery diameter and distension by Doppler frequency analysis of vessel wall movements in M-mode in ten essential hypertensive patients with normal carotid artery IMT (HYP1), in ten patients with increased IMT (HYP2), and in 13 normotensive control subjects (CON).Thereafter, we measured changes in brachial artery (BA) diameters during distal reactive hyperemia after 4 min of forearm occlusion. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation, and BA blood flow was estimated using a pulsed Doppler system. Intima-media thickness of the carotid arteries was examined by high resolution B-mode ultrasound. IMT was 0.66 ± 0.02 mm in the HYP1 group, 0.84 ± 0.03 mm in the HYP2 group (P < .01 v HYP1, P < .01 v CON), and 0.71 ± 0.04 mm in the CON group. Forearm occlusion was reduced in both the HYP1 group (3.4% ± 3.6%, P < .01 v CON) and the HYP2 group (6.4% ± 1.5%, P < .05 v CON) when compared with the CON group (16.5% ± 2.8%). Nitroglycerin-mediated vasodilation and BA blood flow were not different between study groups. BA distension (as well as carotid artery distension) was significantly lower in the HYP1 group (52 ± 6 μm, P < .05 v CON), but not in the HYP2 group (72 ± 10 μm) when compared with the CON group (88 ± 13 μm). The data suggest that endothelial dysfunction and reduced distensibility of large arteries in patients with essential hypertension occur in the absence of structural vessel wall alterations.     

Effect of AT1 receptor blockade on endothelial function in essential hypertension

BACKGROUND: Angiotensin II adversely affects endothelial function and NO availability. We analyzed the effect of AT(1) receptor blockade on endothelium-dependent vasodilation and basal nitric oxide (NO) production and release in hypertensive patients. METHODS AND RESULTS: Sixty patients (53 +/- 10 years) with essential hypertension were randomized to 6 weeks of double-blind therapy with either valsartan (80 mg), hydrochlorothiazide (HCTZ) (25 mg), or placebo once daily. Basal NO production and release was assessed by measuring forearm blood flow (FBF) in response to intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA), and endothelium-dependent vasodilation by measuring FBF in response to intra-arterial administration of acetylcholine, respectively. Intra-arterial infusion of noradrenaline and sodium nitroprusside was used to assess endothelium-independent changes in FBF. Blood pressure (BP) similarly decreased with active treatments (P < .001). After valsartan treatment, the decrease of FBF in response to L-NMMA was augmented (4 micromol/min L-NMMA, -1.3 +/- 1.2 after v -0.5 +/- 1.1 mL/min/100 mL before therapy, P < .02; 8 micromol/min L-NMMA: -1.7 +/- 1.3 after v -1.1 +/- 1.2 mL/min 100 mL before therapy, P < .05). No improvement was found after placebo or HCTZ treatment. Changes in L-NMMA-induced decrease of FBF with valsartan treatment were not related to BP changes. Neither drug substantially modified the response of FBF induced by intra-arterial infusion of acetylcholine, noradrenaline, and sodium nitroprusside. CONCLUSIONS: The AT(1) receptor blockade with valsartan improved basal NO production and release. The effect seems to be BP independent, as BP reduction with HCTZ failed to increase NO availability.