M. J. F. Kool

Short and long-term effects of smoking on arterial wall properties in habitual smokers

OBJECTIVES This study investigated the short-term effects of smoking on hemodynamic function and distensibility and compliance of large arteries in habitual smokers. In addition, the effect of smoking was not measured in nonsmokers, but vessel wall properties were compared between smokers and nonsmokers (basal state). BACKGROUND Smoking is a well known risk factor for atherosclerosis. Loss of distensibility and compliance of large arteries may play a role in the onset of atherosclerosis. METHODS The distensibility and compliance coefficients of the common carotid and brachial arteries were determined from the arterial wall displacement during systole and the end-diastolic diameter by using a vessel wall movement detector and from the pulse pressure as assessed in the upper arm. Cardiac function (cardiac output, stroke volume) was measured with Doppler echocardiography. Systemic vascular resistance was calculated as mean arterial pressure divided by cardiac output. RESULTS In habitual smokers, smoking one cigarette caused a sharp increase in blood pressure (6%) and heart rate (14%). Cardiac index increased (16%), mainly because of the marked increase in heart rate. Stroke and systemic vascular resistance indexes did not change significantly. Smoking enhanced forearm blood flow after wrist occlusion (17%), but total forearm blood flow was unchanged, suggesting an increase in muscle blood flow and a decrease in skin flow. Because of higher blood pressure, the diameter of the elastic common carotid artery increased by 3% (passive phenomenon). Distensibility of the carotid artery decreased (7%), and as a result, carotid compliance was preserved. In contrast, despite higher blood pressure, the diameter of the muscular brachial artery did not change, suggesting an increased vascular tone. Brachial distensibility and compliance decreased (18% and 19%, respectively). Habitual smokers were comparable to nonsmokers with regard to blood pressure, cardiac function, vascular resistance and vessel wall properties of large arteries. Heart rate was higher in habitual smokers (14%). CONCLUSIONS These data indicate that in habitual smokers, smoking one cigarette causes short-term increases in arterial wall stiffness that might be harmful to the artery and increase the risk for plaque rupture. Except for a higher heart rate, no obvious long-term effect of smoking was observed on hemodynamic variables and arterial stiffness. Because acute cardiovascular events are mainly due to plaque rupture, the short-term effects of smoking might be a more important risk than long-term effects for these acute ischemic events.

Vessel Wall Properties of Large Arteries in Uncomplicated IDDM

OBJECTIVE Patients with insulin-dependent diabetes mellitus (IDDM) are at high risk for cardiovascular disease. Arterial distensibility and compliance are vessel wall properties of large arteries. Altered large artery wall properties can be an early feature of vascular dysfunction. This study investigates vessel wall properties in 30 patients with uncomplicated IDDM and 30 matched healthy control subjects. RESEARCH DESIGN AND METHODS Vessel wall properties of the elastic common carotid (CCA) and the muscular femoral (FA) and brachial arteries (BA) were measured with a vessel wall movement detector system. Blood pressure and heart rate were recorded simultaneously with a semiautomated device. Aortic pulse wave velocity was estimated from the carotido-femoral transit time. RESULTS Blood pressure (IDDM patients: 118 ± 10/69 ± 5 mmHg), pulse pressure (IDDM patients: 49 ± 8 mmHg), and heart rate (IDDM patients: 65 ± 9 beats/min) were similar in IDDM patients and control subjects. No statistically significant changes between IDDM patients and control subjects were found for diameter, distensibility, and compliance of the elastic CCA and the muscular BA. Distensibility (IDDM patients: 16.9 ± 6.4 10-3/ kPa; control subjects: 22.4 ± 11.8 10-3/kPa) of the muscular FA was decreased in IDDM (P < 0.05). However, FA compliance (IDDM patients: 0.80 ± 0.23 mm-2/kPa; control subjects: 0.94 ± 0.41 mm2/kPa) and FA diameter (IDDM patients: 7.87 ±1.10 mm; control subjects: 7.57 ±1.11 mm) did not differ statistically between IDDM patients and control subjects. Aortic pulse wave velocity was the same in IDDM patients and control subjects (IDDM patients: 5.1 ± 0.6 m/s). No relation was found between vessel wall properties and duration of disease, actual glucose level, and HbA1c for all three arteries (CCA, BA, and FA). But the groups might have been too small to draw conclusions. CONCLUSIONS The results of the present study show that in this group of patients with uncomplicated IDDM, vessel wall properties of elastic and muscular large arteries were not obviously reduced when compared with healthy control subjects. However, distensibility of the FA was lower in IDDM patients. Early atherosclerotic changes in IDDM frequently occur at this site. A difference related to the duration of diabetes could not be excluded.

Does lowering of cholesterol levels influence functional properties of large arteries

Hypercholesterolaemia is a risk factor for atherosclerosis and induces endothelial dysfunction. Endothelial dysfunction may increase vascular tone and arterial stiffness and as a consequence may decrease arterial distensibility (DC) and arterial compliance (CC). It is hypothesized that lipid-lowering therapy may enhance DC and CC. Therefore, the present study investigates the effect of lipid-lowering therapy with pravastatin on the haemodynamics, DC and CC of the elastic common carotid artery (CCA), and the muscular femoral (FA) and brachial (BA) arteries in patients with primary hypercholesterolaemia. After an 8-week placebo run-in period with a low-cholesterol diet, 19 patients with total cholesterol concentrations of between 6.5 and 9.0 mmol·l−1 and triglyceride concentrations <4 mmol·l−1 entered a double-blind placebo controlled crossover study. Patients received pravastatin 40 mg o.d. or placebo, each for 8 weeks. Throughout the study the lipid-lowering diet was continued. With pravastatin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides were decreased (total cholesterol 26%, LDL-C 35%, triglycerides 16%), while high-density lipoprotein cholesterol (HDL-C) was not changed. Other laboratory values remained within the normal range. Blood pressure, heart rate, cardiac function and systemic vascular resistance were not influenced by pravastatin. Compared to placebo, diameter, distensibility and compliance of all arteries were not statistically significantly changed with pravastatin. These data suggest that, in patients with mild to moderate primary hypercholesterolaemia, short-term lowering of plasma cholesterol does not alter the haemodynamics and vessel wall properties of large arteries.

Effects of antihypertensive agents on local arterial distensibility and compliance.

Distensibility and compliance are important vessel wall properties. Distensibility is related to elastic properties of the arterial wall, and compliance reflects the buffering function of the artery. Distensibility is a determinant of stress on the vessel wall. A decreased distensibility might increase the risk of arterial wall damage. Therefore, a preserved local distensibility might be important in protecting the arterial wall of each particular artery and especially of those arteries that are more susceptible to vascular disease. Local distensibility and compliance of various large arteries can be measured noninvasively with echo tracking techniques. Studies on local distensibility and compliance revealed that with the calcium antagonist verapamil and the angiotensin-converting enzyme inhibitor perindopril arterial compliance increased mainly because of an increase in distensibility, with only a minor effect on arterial diameter. In contrast, the nitrate compound isosorbide dinitrate increased compliance mainly by increasing arterial diameter, without an increase in distensibility. This indicates that an increase in arterial compliance does not automatically imply an increase in arterial distensibility. The effect of antihypertensive drugs may also depend on the vascular territory. The diuretic amiloride/hydrochlorothiazide increased brachial artery compliance but not common carotid artery compliance. During angiotensin-converting enzyme inhibition the effect on arterial compliance was smaller at the carotid than the femoral artery. However, the opposite held for the nitrate compound. These distinctive effects of antihypertensive drugs on arterial distensibility and compliance and on vascular territories may be relevant to pharmacological prevention and management of arterial disease.

Vascular distensibility and compliance in salt-sensitive and salt-resistant borderline hypertension

Objective: To gain insight into the relationship between vascular compliance and sodium sensitivity. Design: Arterial and venous compliance was determined in 17 sodium-sensitive and 28 sodium-resistant, young, borderline hypertensive males and in 10 age-matched normotensive controls, during regular sodium intake. Methods: The carotid, femoral and brachial arteries were studied using a non-invasive ultrasound vessel wall movement detector system, and venous compliance was determined using forearm strain-gauge plethysmography. Cardiac output, plasma volume and hormonal factors, such as plasma renin activity, were also measured to assess their possible influence on vascular compliance. Results: Large artery compliance was significantly less in the sodium-sensitive than in the sodium-resistant subjects in all arteries studied. Compared with controls, arterial compliance was reduced significantly in the sodium-sensitive group, whereas the sodium-resistant group did not differ significantly from the controls. Venous compliance was reduced equally in the two hypertensive groups compared with the controls, although the differences did not reach statistical significance. Cardiac output, blood pressure, plasma volume and hormonal factors did not differ between sodium-sensitive and sodium-resistant subjects and could not have been responsible for the observed differences in arterial compliance. Conclusions: The results of this study suggest that sodium-sensitive borderline hypertensives have reduced large artery compliance compared with age-matched sodium-resistant subjects. Since this finding could not be explained by differences in haemodynamic or hormonal factors between the groups, this suggests alterations to the viscoelastic properties of the arterial walls in sodium-sensitive subjects.

Pharmacological properties of nebivolol in man

ObjectivesThe aims of the present study were to determine (1) the β1-blocking potency and (2) the β1 adrenoceptor selectivity of nebivolol in man after repeated dosing (7 days) compared with that after a single oral intake and with that after atenolol for 7 days. In addition, it was investigated whether (3) nebivolol has α1-blocking properties which might at least in part explain the vasodilating property of the compound.MethodsTwelve healthy subjects were randomized in an open, two-way cross-over study. β1-Blocking potency and β1-adrenoceptor selectivity of nebivolol 5 mg once daily (o.d.) were compared with those of atenolol at three doses (25, 50 and 100 mg) o.d. Measurements were performed after 1 and 7 days of drug intake. β1Adrenoceptor potency was assessed by the percentage decrease in exercise-induced tachycardia (AEIT) during β-blockade. β1-Selectivity of nebivolol and atenolol were investigated using the heart rate response to isoprenaline at equipotent β1blocking dosages of both drugs. α1-Blockade of nebivolol was measured using the phenylephrine dose-response test.ResultsΔEIT after a single oral dose of nebivolol 5 mg (10%) was significantly smaller than after nebivolol 5 mg o.d. for 7 days (15%). After 1 week of treatment no difference was seen in ΔEIT between nebivolol 5 mg o.d. and atenolol 25 mg o.d. (16%). At these dosages the suppression in isoprenaline-induced tachycardia by both drugs did not differ (CD20 ratio 1.7). In contrast to atenolol 25 mg, after 1 week of nebivolol 5 mg o.d., blood pressure decreased. This decrease averaged 10% and — like in a study with hypertensive patients — was similar with that after atenolol 100 mg o.d. None of the phenylephrine test parameters changed from pre-study values after nebivolol.Conclusionsβ1-Blockade of nebivolol 5 mg is larger after repeated dosing than after a single oral intake. After once daily repeated dosing nebivolol 5 mg and atenolol 25 mg are equipotent in β1-antagonism. No difference in β1-selectivity is observed between the two drugs. Nebivolol has no additional α1-blocking property, which may at least in part explain its vasodilating effect.

Effects of diurnal variability and exercise training on properties of large arteries.

Objective To examine the diurnal variability in arterial distensibility and compliance and to study the effects of exercise training on these large artery properties. Design Vessel wall properties of the elastic common carotid and muscular brachial arteries were measured non-invasively with a vessel wall movement detector system in 12 healthy volunteers. Properties of the common carotid, the femoral and the brachial arteries were studied in 15 sedentary males in comparison with 15 male cyclists. Results Diurnal changes in the carotid and brachial arteries were similar. Blood pressure decreased at night while arterial diameter increased. Distensibility decreased and compliance was preserved at night. The vessel wall properties of the carotid artery did not differ between the sedentary males and the cyclists, but the femoral and brachial arteries were more elastic in the cyclists. The diameter of the femoral artery was larger in the cyclists. Conclusions We found a diurnal pattern in changes in diameter and distensibility of elastic and muscular large arteries. Compliance, the buffering capacity of larger arteries, was preserved at night. The supplying femoral artery was larger and more distensible in cyclists. Exercise training did not affect the elastic carotid artery, but improved vessel wall properties of the brachial, and maybe also of other, muscular large arteries.

Disparate effects of antihypertensive drugs on large artery distensibility and compliance in hypertension

Distensibility and compliance are large artery properties, that may be important in cardiovascular disease. Distensibility is a determinant of the pulsatile stress on the vessel wall and is thought important in ageing and atherosclerotic disease. Compliance reflects the buffering capacity of the arteries and is a major determinant of the afterload on the heart. In hypertension large arteries are getting stiffer, resulting in a decreased distensibility and compliance. Decrease in blood pressure by itself can improve large artery properties. Despite a decrease in blood pressure, not all antihypertensive drugs improve large artery properties. Compliance is improved by firstline antihypertensive drugs such as angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers with vasodilating properties, selective beta 1-blockers and some diuretics. Recent data suggest that ACE inhibitors such as perindopril improve distensibility and compliance of large arteries more than diuretics such as amiloride/hydrochlorothiazide. Apart from the indirect effect (decrease in blood pressure), this makes a direct effect of perindopril on large artery properties very likely. ACE inhibitors such as perindopril decrease the afterload on the heart more than diuretics such as amiloride/hydrochlorothiazide by both a more pronounced decrease in systemic vascular resistance and an increase in large artery compliance.

Introduction to large artery properties as a target for risk reduction by antihypertensive therapy

Aim To review the effect of antihypertensive drugs on pulsatile stress and shear stress. Results of data review Mortality and morbidity in hypertension are better correlated with systolic than diastolic blood pressure, indicating a pulsatile stress effect. Distensibility and compliance are large artery properties and important determinants of pulsatile stress. β -Blockers with vasodilating properties, several selective β1-blockers, angiotensin converting enzyme inhibitors and calcium antagonists are first-line antihypertensive drugs that improve these properties of large arteries. The impact of shear stress on the ill effects associated with hypertension is not clear. Conclusion Some but not all classes of antihypertensive drugs can improve large artery properties, and thereby alleviate pulsatile stress.

Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers

SummaryNicorandil (N) and isosorbide dinitrate (ISDN) are vasodilator drugs used in patients with angina. In 24 healthy male volunteers (18–32 years), the acute effect of a single oral dose (20 mg) of N and ISDN on arterial diameter (D), distensibility, and compliance of the elastic common carotid artery (CCA) and the muscular femoral (FA) and brachial (BA) arteries were investigated. The effects on systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and venous hemodynamics were also assessed. In addition, the subacute effects after 8 days of treatment with N (2×20 mg/day) and ISDN (3×20 mg/day) on these parameters were evaluated. After a 20 mg single oral dose, blood pressure decreased significantly more with ISDN (SBP: 6%; DBP: 14%) than with N (SBP: 2%; DBP: 6%), but after 8 days this decrease in blood pressure was not statistically different between ISDN and N. The diameter of CCA increased more with ISDN (11%) than N (5%) acutely as well as subacutely (ISDN: 12%; N: 9%). Heart rate increased only with ISDN (7% acutely, 3% subacutely). No differences between ISDN and nicorandil were found for acute and subacute effects on SVRI, venous hemodynamics, diameter of muscular arteries (FA, BA), and the distensibility and compliance of elastic (CCA) and muscular (FA, BA) arteries. Day 1 to day 8 changes in heart rate and cardiac index were small but differed between ISDN and nicorandil. These differences were due to a smaller increase in HR and CI at day 8 than at day 1 with ISDN. Data on blood pressure and heart rate are in accordance with drug tolerance seen with ISDN but not with nicorandil. However, ISDN drug tolerance was not seen for the diameter of large arteries. In conclusion, with dosages used in angina, compared to nicorandil—a drug with both a potassium channel opening property and a nitratelike action—the pure nitrate ISDN showed a more pronounced decrease in systolic and diastolic blood pressure, a slight increase in heart rate, and more vasodilation of CCA. ISDN drug tolerance was shown for blood pressure and heart rate. In contrast to the well-known venous tolerance during ISDN, there was no ISDN drug tolerance for the effects on diameter of large arteries. No drug tolerance was seen with nicorandil.