RESUMO
Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.
Assuntos
Arginina/farmacologia , Endotélio Vascular/fisiologia , Hipercolesterolemia/fisiopatologia , Vasodilatação/efeitos dos fármacos , Adulto , Arginina/sangue , Feminino , Antebraço/irrigação sanguínea , Humanos , Insulina/sangue , Masculino , Cloreto de Metacolina/farmacologia , Pessoa de Meia-Idade , Óxido Nítrico/fisiologia , Nitroprussiato/farmacologiaRESUMO
OBJECTIVE: Casual (mercury sphygmomanometer) and ambulatory blood pressure measurements were determined in 61 subjects with sustained essential hypertension. DESIGN: Patients were classified into three subgroups: smokers or non-smokers; patients with or without hyperglycemia; and patients with or without plasma lipoprotein abnormality. Mean casual blood pressure were shown to be identical in these three subgroups. RESULTS: When ambulatory blood pressure was analyzed, smokers exhibited a significant increase in pulse pressure exclusively during the activity period, whereas diastolic blood pressure and mean arterial pressure (MAP) were not modified in comparison with controls. Patients with abnormal plasma glucose showed a significant increase in systolic and pulse pressure during both activity and non-activity periods, with a slight increase in MAP during the activity period. Patients with and without plasma lipid abnormality displayed similar ambulatory blood pressure. CONCLUSION: The study provides evidence that, in spite of similar casual blood pressure levels among smokers and non-smokers, as well as among those with elevated fasting glucose levels, smokers and patients with hyperglycemia have a higher systolic and pulse pressure during 24-h monitoring, pointing to the possible role of cyclic stress in the deterioration in the structure of the hypertensive arterial wall.
Assuntos
Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Colesterol/sangue , Hipertensão/fisiopatologia , Fumar/epidemiologia , Monitores de Pressão Arterial , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Blood pressure, heart rate, common carotid and brachial arterial hemodynamics using pulsed Doppler flowmetry and pulse wave velocity determinations were evaluated using a double-blind crossover design versus placebo in 14 patients with sustained essential hypertension treated by the selective beta 1 blocking agent bisoprolol. Blood pressure and heart rate significantly decreased after bisoprolol, whereas no significant change occurred in the diameter, the blood flow and in the vascular resistance of the carotid and brachial circulations. Pulse wave velocity significantly decreased in the brachioradial and the carotid femoral areas. The decrease in the latter was -1.6 +/- 0.8 m/s with bisoprolol and -0.06 +/- 0.80 m/s with placebo (p = 0.001). Brachial artery compliance significantly increased from 117 +/- 49 to 205 +/- 84 cm4 x dynes-1 x 10(9) (p = 0.001), indicating that the antihypertensive effect of beta 1 blockade is associated with an improvement in the viscoelastic properties of the brachial artery wall.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Propanolaminas/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Análise de Variância , Bisoprolol , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/efeitos dos fármacos , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Propanolaminas/uso terapêutico , UltrassonografiaRESUMO
Antihypertensive agents are routinely studied in terms of changes in the level of systolic, diastolic, and mean arterial pressure. Pulse pressure may be independently modified from these parameters as a consequence of specific changes in the mechanical properties of the large arteries and in the timing of incident and reflected pressure waves. The aim of this study was to evaluate the changes in pulse pressure produced by acute calcium blockade by the dihydropiridine derivative, lacidipine, in a double-blind design versus placebo in 18 subjects with mild to moderate hypertension. Carotid and femoral pressure waveforms were recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Early (Pi) and mid-to-late (Ppk) systolic peaks of carotid pressure waveform were evaluated, enabling the effect of incident pressure wave to be quantified as the ratio of Pi to the total height of carotid pulse wave (PP) (Pi/PP) and the effect of wave reflections as the ratio (Ppk-Pi)/PP. Travel time of the reflected wave (delta tp) was timed from the foot of the pressure wave to the foot of the late systolic peak. Pulsatile changes in diameter were studied using noninvasive echo-tracking techniques. Whereas mean arterial pressure significantly decreased following lacidipine, pulse pressure measured at three different sites (brachial, carotid, and femoral arteries) was unchanged. Carotid-femoral pulse wave velocity, carotid and femoral arterial stiffness, and delta tp were not modified, whereas the (Ppk-Pi)/PP ratio and left ventricular ejection time was significantly reduced and the Pi/PP ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Artérias/fisiopatologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Hipertensão/fisiopatologia , Artérias/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiopatologia , Diástole/fisiologia , Di-Hidropiridinas/uso terapêutico , Método Duplo-Cego , Elasticidade , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Sístole/fisiologiaRESUMO
AIM: The assumption that the arterial wall behaves like incompressible material simplifies the analysis of arterial wall elasticity. Experimental evidence for the incompressibility assumption has been obtained directly by volume-displacement and radiological methods. Recent developments in ultrasound technology have made it possible to take direct, high-resolution measurements of the internal diameter and wall thickness of an artery and thus calculate the cross-sectional area of the arterial wall. The objective of this study was to determine the cross-sectional area of the arterial wall in vitro at different levels of strain in order to demonstrate the incompressibility assumption. METHODS: Two different types of fresh, human, medium-sized arteries were studied, the internal mammary artery, and a less elastic and more muscular artery, the radial artery. The internal diameter and wall thickness were measured with an ultrasonic echo-tracking device (NIUS 1; Asulab, Neuchâtel, Switzerland) over 1-min steps of increasing intra-arterial pressure (0, 50, 100, 150 and 175 mmHg). RESULTS: The cross-sectional area of the arterial wall of the radial and internal mammary artery remained unchanged under different levels of strain. CONCLUSION: Since the artery length remained constant during the pressure increases, the lack of change in the cross-sectional area of the arterial wall suggests that the arterial wall of human medium-sized arteries is essentially incompressible.
Assuntos
Artérias/anatomia & histologia , Pressão Sanguínea/fisiologia , Artérias/diagnóstico por imagem , Artérias/fisiologia , Complacência (Medida de Distensibilidade) , Humanos , Técnicas In Vitro , Artéria Torácica Interna/anatomia & histologia , Artéria Torácica Interna/diagnóstico por imagem , Artéria Torácica Interna/fisiologia , Artéria Radial/anatomia & histologia , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiologia , UltrassonografiaRESUMO
AIM: Hypertension has been reported to accelerate the alterations in large arteries induced by ageing. Distal large arteries have been poorly investigated in contrast to proximal large arteries. The objectives of this cross-sectional study were (1) to compare the storage capacity of different arterial sites in normotensive subjects or hypertensive patients; and (2) to compare the different arterial sites with respect to the effects of ageing on storage capacity, in normotensives and in hypertensives. METHODS: Two recently developed ultrasonic echo-tracking devices, offering a high resolution for the assessment of internal arterial diameter and its systolo-diastolic variations, were used to measure end-diastolic diameter, absolute (change at end-systole minus change at end-diastole) and relative (absolute change divided by change at end-diastole) changes in diameter with stroke and the absolute change in cross-sectional area (3.14 x the end-diastolic diameter x half the absolute stroke change in diameter) at the site of the common carotid artery, the abdominal aorta, the common femoral artery, the brachial artery and the radial artery in 50 untreated essential hypertensive patients and 32 normotensive subjects. RESULTS: In both groups, the end-diastolic diameter increased with age for the common carotid artery and the abdominal aorta but not for the common femoral, brachial or radial arteries. In the normotensives, the relative stroke change in diameter was negatively correlated with age for the common carotid artery (P < 0.001) and the abdominal aorta (P < 0.001), and not correlated for the common femoral, brachial and radial arteries. In hypertensives, the relative stroke change in diameter was negatively correlated with age for the common carotid artery (P < 0.05) and the abdominal aorta (P < 0.05), positively correlated with age for the common femoral (P < 0.05) and the radial arteries (P < 0.05) and not correlated for the brachial artery. Similar results were observed for the relationships between the absolute change in cross-sectional area and age. CONCLUSIONS: In hypertensives, enlargement of the proximal large arteries offsets the decrease in the relative stroke change in diameter and maintains an adequate storage capacity. It thus appears that ageing exerts opposing effects on central elastic large arteries and distal muscular medium-sized arteries.
Assuntos
Envelhecimento/fisiologia , Artérias/fisiologia , Hipertensão/fisiopatologia , Adulto , Idoso , Artérias/anatomia & histologia , Artérias/diagnóstico por imagem , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Complacência (Medida de Distensibilidade) , Estudos Transversais , Diástole/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sístole/fisiologia , UltrassonografiaRESUMO
Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acetylcholine (0.3-9.0 micrograms/kg/min) and nitroprusside (0.3-9.0 micrograms/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits.
Assuntos
Arginina/farmacologia , Endotélio Vascular/fisiologia , Hipercolesterolemia/fisiopatologia , Óxido Nítrico/biossíntese , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Arginina/metabolismo , Colesterol na Dieta/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Membro Posterior/irrigação sanguínea , Hipercolesterolemia/metabolismo , Nitroprussiato/farmacologia , Coelhos , Projetos de PesquisaRESUMO
BACKGROUND: Reduced synthesis of endothelium-derived relaxing factor (EDRF) may explain impaired endothelium-dependent vasodilation in hypercholesterolemia. Accordingly, we designed studies to determine if endothelium-dependent relaxation in hypercholesterolemic rabbits may be restored by supplying L-arginine, the precursor of EDRF. METHODS AND RESULTS: Normal or hypercholesterolemic rabbits received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes. Subsequently, animals were killed, thoracic aortas were harvested, and vascular rings were studied in vitro. Rings were contracted by norepinephrine and relaxed by acetylcholine chloride or sodium nitroprusside. Vasorelaxation was quantified by determining the maximal response (expressed as percent relaxation of the contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as -log M). In vessels from hypercholesterolemic animals receiving vehicle, there was a fivefold rightward shift in sensitivity to acetylcholine compared with normal animals (p = 0.05, n = 5 in each group). In vessels from hypercholesterolemic animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16% versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05 versus vehicle). Arginine did not affect maximal and EC50 responses to acetylcholine in vessels from normal animals. Arginine did not potentiate endothelium-independent responses in either group. CONCLUSIONS: We conclude that the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.