Ulrika Hägg

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.

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/m2) 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.

Occurrence of neurotrophin receptors and transmitters in the developing Xenopus gut

Abstract. The ontogeny of gut innervation in the anuran amphibian Xenopus laevis was studied using immunohistochemistry on sections of whole larvae from NF stages 38–52. Immunoreactivity to acetylated tubulin confirmed the presence of nerve fibres as early as stages 38–39. Actin immunoreactivity was found at stage 41, indicating the presence of smooth muscle cells. Trk-like neurotrophin receptors were occasionally found in nerve fibres as soon as stages 38–39. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivities coexisted in nerves innervating the gut wall from stages 40–41, and nitric oxide synthase (NOS) from stage 42. Substance P/neurokinin A (SP/NKA) occurred at stage 42. In all these cases, the first fibres were observed in the oesophagus. Calcitonin gene-related peptide (CGRP) was first observed in nerves at stage 48. In general, VIP/PACAP and NOS innervation was denser than the tachykinin innervation. In conclusion, the development of nerve fibres in the Xenopus gut is probably dependent on neurotrophins that may act via Trk-like receptors and occur before the gut wall is fully organised morphologically. Feeding in Xenopus larvae starts at NF stage 45. The study demonstrates that several of the transmitters investigated are expressed in the gut innervation (and in endocrine cells) prior to this stage.

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 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.

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.

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.