Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m), (age 37+/-11 yrs), (BMI 24+/-3 kg/m(2)) direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA) were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT) technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index), was within the normal range (1.9-3.3) and MSNA was as expected for age and gender (13-44 burst/minute). RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005). RH-PAT index and MSNA were reciprocally related to time (h/week) spent on physical activity (p = 0.005 and p = 0.006 respectively) and platelet concentration (PLT) (p = 0.02 and p = 0.004 respectively). CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular health.

Epidermal growth factor levels are related to diastolic blood pressure and carotid artery stiffness.

OBJECTIVES: The epidermal growth factor (EGF) is believed to be involved in vascular remodelling. EGF receptors are expressed in human atherosclerotic tissue. DESIGN: In order to study the role of EGF in vascular remodelling and early progression of atherosclerosis, 17 men and 16 women aged 20 to 45 years were recruited. Common Carotid Artery Stiffness index (CCA SI) and blood pressure were evaluated. In addition, serum levels of EGF and blood lipids were measured. RESULTS: The levels of serum EGF were significantly correlated to diastolic blood pressure (p<0.05) and CCA SI (p<0.05). Subjects with EGF concentrations in the upper median had significantly lower levels of HDL (High Density Lipoproteins) (p<0.05) and ApoA1 (Apolipoprotein) (p<0.05) than those with EGF concentrations in the lower median. DISCUSSION: High serum level of EGF is associated with elevated diastolic blood pressure and increased vessel stiffness suggesting a possible functional role of EGF in the cardiovascular system in a healthy population.

Non-invasive real-time imaging of atherosclerosis in mice using ultrasound biomicroscopy.

There are increasing needs to develop imaging techniques to study in vivo vascular morphology and function in various mouse models of atherosclerosis. Using ultrasound biomicroscopy (UBM), we developed and validated a new imaging protocol to follow lesion progression in atherosclerotic mice. ApoE and LDL receptor double knockout mice (DKO) with various degree of atherosclerosis and normal control mice were imaged at the level of the ascending aorta using UBM. Average plaque thickness, as well as plaque area were delineated in the short-axis images, and were subsequently compared with histological measurements. We showed that plaque area at this vascular site was closely correlated to total plaque burden from en face measurement (p<0.0001). UBM-measured plaque thickness and area correlated with indices for histology measures from the same vascular region (p<0.0001 respective p<0.0001). Furthermore, in 16 DKO mice aged from 32 to 35 weeks, UBM showed significantly weekly increases of IMT in the ascending aorta from 0.106+/-0.108 mm at 32 weeks of age to 0.256+/-0.345 mm at 35 weeks of age (p=0.0002). In conclusion, this novel imaging protocol provides us with a non-invasive, accurate and inexpensive way to follow lesion progression in mice in vivo.

Proximal to middle left coronary artery flow velocity ratio, as assessed using color Doppler echocardiography, predicts coronary artery atherosclerosis in mice.

BACKGROUND: We aimed to establish a completely noninvasive technique to assess coronary artery atherosclerosis in living mice using proximal to middle left coronary artery (LCA) velocity ratio as assessed with color Doppler echocardiography (CDE). METHODS AND RESULTS: Three groups of apolipoprotein E/low-density lipoprotein receptor double-knockout (apoE/LDLr dko) mice 10, 40, and 80 weeks of age and 3 additional age-matched groups of C57BL/6 mice were examined under anesthesia. Coronary flow velocity in proximal (Vprox) and middle part (Vmid) of LCA was measured using CDE. A 40-MHz ultrasound biomicroscope (UBM) was used to visualize lumen and outer vessel diameter in the proximal LCA. Flow velocity in the proximal LCA increased significantly with age and remained constant in the middle part in the apoE/LDLr dko mice, whereas velocities at both the sites remained unchanged in C57 mice. CDE-assessed flow velocity ratio (Vprox/Vmid) increased significantly with age in apoE/LDLr dko mice (P=0.0055) and correlated significantly to percentage wall thickness, as assessed by UBM (P=0.0044; r=0.65) and histology (P=0.0002; r=0.78). Wall thickness increased with age in the apoE/LDLr dko mice as measured with UBM (P=0.0093; r=0.49), which was also confirmed with histology (P<0.0001; r=0.73). CONCLUSIONS: CDE and UBM are useful noninvasive tools to quantify mouse coronary artery atherosclerosis in vivo.

Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults.

Short-term exercise training has been shown to improve cardiovascular function, whereas long-term effects of a physically active lifestyle, on coronary artery function in particular, are still not well studied. We explored possible relationships between physical exercise capacity and coronary and peripheral vascular function in healthy young adults. Twenty-nine healthy young male and female volunteers participated in the study. They underwent 1) basic clinical and echocardiographic characterization, 2) coronary flow velocity reserve (CFVR) measurement of the left anterior descending coronary artery (LAD), 3) common carotid artery (CCA) intima-media thickness (IMT) measurement, 4) assessment of CCA stiffness index (SI), 5) forearm flow-mediated vasodilation (FMD), and 6) submaximal exercise test. The calculated weight-adjusted maximal oxygen uptake capacity (Vo(2 max)(c)) was positively correlated to LAD CFVR and inversely correlated to IMT and SI. Also, subjects with high compared with moderate exercise capacity had higher FMD. In addition, subjects with LAD CFVR in the upper median had greater ratios between endothelium-dependent and -independent vasodilation in the forearm and lower SI in CCA. High exercise capacity due to a physically active lifestyle is associated with high coronary and peripheral artery function, indicating an early protective role of physical exercise for cardiovascular health.

A short period of apnoea causes a marked increase in coronary flow velocity: a transthoracic pulsed wave Doppler study.

Coronary artery flow velocity during a short period of apnoea was investigated by transthoracic Doppler recording in 10 healthy men, aged 24-52. During breath holding for 29 +/- 6 s the oxygen saturation in the finger, measured by pulse oxymetry, decreased from 97.5 +/- 0.8 to 90.0 +/- 3.2% (P < 0.001). The maximal coronary blood flow velocity in the left anterior descending artery increased by 62% from 0.26 +/- 0.09 to 0.42 +/- 0.10 m s(-1) and the mean diastolic flow velocity by 47% from 0.19 +/- 0.04 to 0.28 +/- 0.08 m s(-1) (P < 0.001). In most subjects the increase of velocity started already after a few seconds of apnoea. Besides theoretical implications the results show that it is very important to be aware of the higher velocity during apnoea in order to avoid misinterpretation when using breath holding during magnetic resonance imaging or Doppler recording of coronary flow.

Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins.

Physical exercise is considered to be beneficial for cardiovascular health. Nevertheless, the underlying specific molecular mechanisms still remain unexplored. In this study, we aimed to investigate the effects of voluntary exercise on vascular mechanical properties and gene regulation patterns in spontaneously hypertensive rats. By using ultrasound biomicroscopy in an ex vivo perfusion chamber, we studied the distensibility of the thoracic aorta. Furthermore, exercise-induced gene regulation was studied in aortae, using microarray analysis and validated with real-time PCR. We found that distensibility was significantly improved in aortas from exercising compared with control rats (P < 0.0001). Exercising rats demonstrated a striking pattern of coordinated downregulation of genes belonging to the heat shock protein family. In conclusion, voluntary exercise leads to improved vessel wall distensibility and reduced gene expression of heat shock protein 60 and 70, which may indicate decreased oxidative stress in the aortic vascular wall.

Voluntary physical exercise and coronary flow velocity reserve: a transthoracic colour Doppler echocardiography study in spontaneously hypertensive rats.

In the present study, we have developed and demonstrated a coronary artery imaging protocol in rats using transthoracic high-frequency CDE (colour Doppler echocardiography) to investigate the potential direct effects of exercise on CFVR (coronary flow velocity reserve). SHR (spontaneously hypertensive rats) performed voluntary exercise for 6 weeks. Rats were then submitted to ultrasonographic examination and CFVR measurements. The LAD (left anterior descending coronary artery) was visualized using transthoracic CDE in a modified parasternal long-axis view. Doppler measurement was made in mid-LAD during baseline and adenosine-induced hyperaemic condition. Gene and protein expression in cardiac tissue were studied using real-time PCR and immunohistochemistry. Adenosine infusion significantly (P<0.001, as determined by ANOVA) decreased HR, without affecting blood pressure in anaesthetized SHR. A significantly greater adenosine dose-dependent response was seen in exercised rats compared with controls (P=0.02, as determined by ANOVA). The baseline flow velocity in mid-LAD was 0.33+/-0.06 and 0.41+/-0.14 m/s in the exercised and control animals respectively (P value was not significant). The maximum adenosine-induced response was reached at a dose of 140 microg.kg-1 of body weight.min-1, and CFVR averaged at 2.6+/-0.53 and 1.5+/-0.24 in exercised and control animals respectively (P<0.01). Gene expression of CuZnSOD was up-regulated by 21% in exercised animals compared with controls (1.1+/-0.16 compared with 0.89+/-0.09; P<0.01), whereas eNOS expression was unchanged. In conclusion, CFVR in rats can be non-invasively assessed using CDE with high feasibility. Physical exercise is associated with improved CFVR and antioxidative capacity in SHR.

Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE-/- mice.

Flow-mediated vasodilation is suggested as one of the mechanisms involved in arterial expansive remodelling, which is thought to be a defence mechanism in atherogenesis. In the present study, we tested the hypothesis that lumen obstructive plaque formation is associated with failure of NO (nitric oxide)-dependent vasodilation in conduit vessels. Cardiac function and aortic root flow velocities were assessed using high-resolution echocardiography and two-dimensional-guided pulsed Doppler in ApoE(-/-) (apolipoprotein E-deficient) mice fed a standard or high-cholesterol diet. Endothelial function in the proximal and mid-descending aortic regions was studied using a myograph technique. Flow velocity at the aortic root of cholesterol-fed ApoE(-/-) mice was significantly increased as a result of lumen narrowing, detected via histological analysis. NO-dependent vasodilatory responses were selectively impaired in the atherosclerosis-prone vascular regions in cholesterol-fed ApoE(-/-) mice. In conclusion, consumption of a high-cholesterol diet results in lumen obstructive plaque formation in ApoE(-/-) mice, which significantly alters aortic root haemodynamics. This phenomenon is associated with impaired NO-dependent vasodilation in vessel segments known to be prone to atherosclerosis.

Voluntary physical exercise-induced vascular effects in spontaneously hypertensive rats.

Forced training has been shown to have beneficial vascular effects in various animal exercise models. In the present study, we explored possible physiological and molecular effects of voluntary physical exercise on various vascular beds. SHR (spontaneously hypertensive rats) performed voluntary exercise for 5 weeks in a computerized wheel cage facility. Ex vivo myograph studies revealed an increased sensitivity of the ACh (acetylcholine)-mediated vasodilation in resistance arteries of the exercised animals (ED50=15.0+/-3.5 nmol/l) compared with the controls (ED50=37.0+/-8.8 nmol/l; P=0.05). The exercise/control difference was abolished after scavenging reactive oxygen radicals. In conduit arteries, ACh induced a similar vasodilatory response in both groups. The in vivo aortic wall stiffness, assessed by means of Doppler tissue echography, was significantly lower in the exercising animals than in controls. This was demonstrated by significantly increased peak systolic aortic wall velocity (P=0.03) and the velocity time integral (P=0.01) in exercising animals compared with controls. The relative gene expression of eNOS (endothelial nitric oxide synthase) was similar in both groups of animals, whereas Cu/ZnSOD (copper/zinc superoxide dismutase) gene expression was significantly increased (+111%; P=0.0007) in the exercising animal compared with controls. In conclusion, voluntary physical exercise differentially improves vascular function in various vascular beds. Increased vascular compliance and antioxidative capacity may contribute to the atheroprotective effects associated with physical exercise in conduit vessels.