bluuebunny/crossref_metadata_2025 huggingface dataset:
Total blood volume in endurance‐trained postmenopausal females: relation to exercise mode and maximal aerobic capacity
Authors: Jones P. Parker , Davy K.P. , Desouza C.A. , Tanaka H.
Published: March 2003

We have recently shown that postmenopausal female distance runners demonstrate elevated levels of blood volume compared with sedentary healthy peers. We also found a strong positive relation between blood volume and maximal oxygen consumption. In young adult males, endurance exercise training increases blood volume when performed in the upright, but not in the supine body position. Based on these observations, we hypothesized that among postmenopausal females, the elevation in blood volume would be absent or attenuated in women who train in the horizontal vs. upright body position, and that the lower blood volume in the former would be associated with lower maximal aerobic capacity. Thus, we measured supine resting plasma and total blood volumes (Evans blue dye) and maximal oxygen consumption in postmenopausal women: 10 sedentary controls, 10 swimmers and 10 runners matched for age (60 ± 2; 59 ± 2; 58 ± 2 years, mean ± SE) and hormone replacement use (5 per group). The swimmers and runners were further matched for training volume (4.5 ± 0.2 vs. 4.8 ± 0.6 h week–1), relative performance (78 ± 5 vs. 75 ± 3% of age‐group world record) and fat‐free mass (45.5 ± 0.8 vs. 44.9 ± 1.5 kg). Total blood volume and maximal oxygen consumption were highest in the runners (81.2 ± 4; 52.4 ± 3 mL kg–1, respectively) and progressively lower in the swimmers (68.8 ± 3; 44.2 ± 2) and controls (59.2 ± 2; 37.9 ± 2; all P < 0.05). In the pooled population, blood volume was positively related to maximal oxygen consumption (r= 0.72, P < 0.0001). We conclude that in endurance‐trained postmenopausal females matched for training volume and competitive performance: (1) blood volume is lower in those who train in the horizontal (swimmers) compared with the upright position (runners); (2) the lower blood volume is associated with a lower maximal aerobic capacity. Nevertheless, blood volume and maximal oxygen consumption are higher in postmenopausal women who train in the horizontal position than in sedentary controls.
Conducted vasomotor responses in arterioles: characteristics, mechanisms and physiological significance
Authors: Gustafsson  , Holstein‐Rathlou
Published: March 2003

Micropipette application of certain vasoconstrictor or ‐dilator substances onto the surface of arterioles induces both a local vasomotor response and a response which is propagated up‐ and downstream along the vessel, a so‐called conducted vasomotor response. In some vascular beds conducted vasoconstrictor and dilator responses are detectable more than a millimetre from the site of agonist delivery. While agonists such as acetylcholine, noradrenaline, and KCl almost invariably give rise to conducted vasomotor responses others, such as sodium nitroprusside or vasopressin, do not. Conducted vasomotor responses in arterioles appear to rely on passive electrotonic spread of the change in membrane potential induced by the agonist at the tip of the pipette. Presumably the current spreads up‐ and downstream along the arteriolar wall through endothelial or smooth muscle cell gap junctions. Whether the electrical signal is conducted primarily through the endothelial or the smooth muscle cell layer or both is currently not known, but it may depend on the agonist used. Experiments have suggested that conducted vasodilation in skeletal muscle feed arterioles plays an important role in the development of functional hyperaemia at the onset of exercise. In the kidney, conducted vasoconstriction is believed to be responsible for the upstream contraction of the afferent arteriole and interlobular artery known to occur in response to activation of the macula densa. Therefore conducted vasoconstriction could be important for the tubuloglomerular feedback mechanism. Finally, experimental studies have shown that conduction of vasomotor responses in arterioles may be altered in pathological conditions associated with microvascular dysfunction such as arterial hypertension and sepsis.
A pivotal role of nitric oxide in endothelial cell dysfunction
Authors: Goligorsky  , Noiri  , Tsukahara  , Budzikowski  , Li
Published: March 2003

The functional role of the vascular endothelium is a subject of growing interest and appreciation. Some of the key functions of the endothelium are modulated by the activity and expression of endothelial nitric oxide synthase (eNOS), suggesting a role for this enzyme in endothelial dysfunction. Several well‐known angiogenic stimulators exert their effect only in the presence of the functional eNOS. In this setting NO production is responsible for the scalar podokinetic cell motility, which is a prerequisite for the acquisition of vectorial movement when guidance cues are applied. The mode of this NO action appears to lie in the accelerated turnover of focal adhesions through the process of activation/inactivation of protein tyrosine phosphatases. Localization of eNOS to the caveolar domains, in the proximity of clustered β1 integrins, provides an additional level of regulatory complexity through the modulation of caveolar dynamics and the state of caveolin oligomerization. Therefore, eNOS serves various important functions in the endothelium and is a putative target for therapeutic interventions.
Nitric oxide: a physiological mediator of the type 2 (AT2) angiotensin receptor
Authors: Carey  , Jin  , Wang  , Siragy
Published: March 2003

Virtually all of the biological actions of angiotensin II (ANG II) have been thought to be mediated by the type 1 (AT1) angiotensin receptor and the function of the type 2 (AT2) receptor is unknown. We now describe a novel physiological action of ANG II to release nitric oxide (NO) mediated by the AT2 receptor in both the kidney and gastrointestinal tract. We present an integrated model for a counter‐regulatory protective action of the AT2 receptor mediated by nitric oxide. In the kidney, ANG II at the AT2 receptor stimulates a vasodilator cascade of bradykinin (BK), NO and cyclic GMP which is tonically activated only during conditions of increased ANG II, such as sodium depletion. In the absence of the AT2 receptor, pressor and antinatriuretic hypersensitivity to ANG II is associated with BK and NO deficiency. In angiotensin‐dependent hypertension, the hypotensive effect at AT1 receptor blockade is due at least in part to AT2 receptor stimulation and consequent increased activity of the vasodilator cascade. In the gastrointestinal tract, physiological quantities of ANG II stimulate the AT2 receptor releasing NO and cGMP leading to increased sodium and water absorption. In conclusion, NO is an important physiological mediator of ANG II at the AT2 receptor.
Molecular mechanisms controlling nutritive blood flow: role of cytochrome P450 enzymes
Authors: Harder D.R. , Roman R. J. , Gebremedhin D.
Published: March 2003

This short review summarizes the potential role of cytochrome P450 (P450) in regulating blood flow in the brain tissue and in the skeletal muscle. We provide data showing that pressure‐induced myogenic activity in the brain is largely responsible for autoregulation of CBF. This myogenic response to pressure is maintained, in part, by 20‐HETE formation in arterial muscle cells through a P450 ω‐hydroxylase coded for by a P450 4A cDNA. Autoregulation of CBF is a hallmark of the cerebral circulation and provides adequate nutritive blood flow despite large fluctuations in arterial pressure. Given the importance of oxidative metabolism in the brain, support of neuronal activity is mediated by functional hyperaemia to active neurones providing adequate delivery of oxidative substrate. We provide data demonstrating that this functional hyperaemia in the brain is regulated by astrocytes which sense neural activity and release dilator metabolites which shunt blood flow to active neurones. One of the metabolites released by astrocytes in this regard are epoxygenated products of arachidonic acid (AA) formed by P450 enzymes. These AA metabolites of P450 enzymes are epoxyeicosatrienoic acid (EETs). One of these P450 enzymes is coded by a 2C11 cDNA present in astrocytes. Furthermore, astrocytes are capable of inducing capillary angiogenesis which appears to be mediated, in part, by P450‐derived EETs.
Endogenous nitric oxide in the control of skeletal muscle oxygen extraction during exercise
Authors: Shen W. , Xu X. , Ochoa M. , Zhao G. , Bernstein R.D. , Forfia P. , Hintze T.H.
Published: March 2003

Our previous studies uncovered an inhibitory effect of nitric oxide (NO) on leg skeletal muscle respiration in dogs at rest. The role of NO in the modulation of O2 consumption and O2 extraction in hindlimb muscle during elevated metabolic states was investigated in chronically instrumented dogs while walking and at three exercise intensities which markedly increased hindlimb blood flow. Walking resulted in increased O2 consumption by 17 ± 4 mL min−1 and O2 extraction from 24 ± 1 to 37 ± 8%, with no alteration in hindlimb blood flow (BFLeg) and vascular resistance (VRLeg). Running at the highest speed (9.1 mph) resulted in an increase in BFLeg from 0.67 ± 0.05 to 2.2 ± 0.1 L min−1, a reduction of VRLeg and elevation of hindlimb O2 consumption from 33 ± 3 to 226 ± 21 mL min−1 and O2 extraction from 29 ± 2 to 61 ± 5%, with a decrease in leg venous PO2 from 38 ± 1 to 25 ± 1 mmHg. After nitro‐L‐arginine (NLA) (35 mg kg−1, i.v.) to inhibit endogenous NO synthesis, walking caused greater increases in hindlimb O2 consumption (29 ± 5 mL min−1) and O2 extraction (43 ± 1 to 60 ± 3%) (both P < 0.05), with no significant change in BFLeg. During running at the highest speed, BFLeg was 1.9 ± 0.1 L min−1 (P < 0.05) and VRLeg was higher, accompanied by increases in hindlimb O2 consumption from 49 ± 7 to 318 ± 24 mL min−1 and O2 extraction from 41 ± 2 to 79 ± 4% (both P < 0.05), with a greater decrease in leg venous PO2 from 33 ± 1 to 20 ± 1 mmHg (P < 0.05). Similar results were found for intermediate levels of exercise. Our results indicate that NO modulates hindlimb skeletal muscle O2 extraction and O2 usage whether blood flow increased or not during exercise.
Modulation of Na+× H+ exchange by osmotic shock in isolated bovine articular chondrocytes
Authors: Yamazaki  , Browning  , Wilkins
Published: March 2003

The effects of hyperosmotic shock on intracellular pH (pHi) have been characterized in bovine articular chondrocytes. Osmotic shock is one of a variety of physicochemical stimuli experienced by chondrocytes upon cartilage loading. Cells were isolated from their extracellular matrix, and loaded with the pH‐sensitive fluorophore 2′,7′‐bis(carboxyethyl)‐5(6)‐carboxyfluorescein. Hyperosmotic shocks were imposed by addition of KCl or sucrose to the extracellular medium. For cells at steady‐state pHi, resuspension in hyperosmotic solutions elicited an alkalinization, which was significantly inhibited by removal of extracellular Na+ ions, or treatment with amiloride (1 m
M) or HOE‐694 (10 μM), both inhibitors of Na+ × H+ exchange. For cells acidified by ammonium rebound, recovery of pHi towards resting levels was significantly stimulated by exposure to hyperosmotic solutions, and the effect was again attenuated by inhibition of Na+ × H+ exchange. Determination of the rate of acid extrusion at different levels of acidification indicated that the affinity of acid extrusion systems for H+ ions was increased by hypertonic shock. The response to hyperosmotic media could be abolished by treatment of chondrocytes with the non‐specific kinase inhibitor staurosporine (10 n
M), while the phosphatase inhibitor okadaic acid (1 m
M) was able to augment recovery rates to values similar to those measured under hyperosmotic conditions. The osmotic sensitivity of recovery was unaffected by exposure to the protein kinase C inhibitor calphostin C, but was abolished in cells treated with ML‐7, a specific inhibitor of myosin light chain kinase. These results confirm that – as for other components of mechanical load – increased osmolarity can modulate the activity of Na+ × H+ exchange, in this case by altered patterns of phosphorylation of transporter‐associated myosin. The changes of pHi which will result dictate in part the rate of cartilage macromolecule synthesis.
Effect of combined supplementation with vitamin E and alpha‐lipoic acid on myocardial performance during in vivo ischaemia‐reperfusion
Authors: Coombes  , Powers  , Demirel  , Jessup  , Vincent  , Hamilton  , Naito  , Shanely  , Sen  , Packer  , Ji
Published: March 2003

Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia‐reperfusion (I‐R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha‐lipoic acid (α‐LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I‐R. The purpose of these experiments was to investigate the effects of VE and α‐LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I‐R insult. Female Sprague–Dawley rats (4‐months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and α‐LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN‐93M standards, which contains 75 IU VE kg–1 diet. The ANTIOXID diet contained 10 000 IU VE kg–1 diet and 1.65 g α‐LA kg–1 diet. After the 14‐week feeding period, significant differences (P < 0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I‐R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P > 0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I‐R protocol. Following I‐R, two markers of lipid peroxidation were lower (P < 0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and α‐LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in vivo I‐R in young adult rats.
Diversity of responses of renal cortical and medullary blood flow to vasoconstrictors in conscious rabbits
Authors: Evans  , Madden  , Denton
Published: March 2003

The medullary microcirculation receives only about 10% of total renal blood flow, but plays a critical role in long‐term arterial pressure regulation, so we need to better understand its regulation. Although there is evidence that circulating and locally acting hormones can differentially affect cortical and medullary blood flow in anaesthetized animals, there is little information from studies in conscious animals. This study is aimed (i) to develop a method for chronic measurement of cortical and medullary blood flow in conscious rabbits, and (ii) to test whether renal cortical and medullary blood flow can be differentially affected by intravenous (i.v.) infusions of various vasoconstrictor hormones in conscious rabbits. At preliminary operations, rabbits were equipped with single‐fibre laser‐Doppler flowprobes in the (left) renal cortex and medulla, and Transonic flowprobes for measuring cardiac output and renal blood flow. Intravenous angiotensin II (300 ng kg–1 min–1), [Phe2,Ile3,Orn8]‐vasopressin (30 ng kg–1 min–1), noradrenaline (300 ng kg–1 min–1), endothelin‐1 (20 ng kg–1 min–1) and N G‐nitro‐
L‐arginine (10 mg kg–1) increased mean arterial pressure (by 10–45% of baseline) and reduced heart rate (by 16–35%) and cardiac output (by 16–45%). Consistent with previous observations in anaesthetized rabbits, all treatments except [Phe2,Ile3,Orn8]‐vasopressin reduced renal blood flow (13–63%) and cortical blood flow (16–47%), but medullary blood flow was significantly reduced only by [Phe2,Ile3,Orn8]‐vasopressin (41%) and N G‐nitro‐
L‐arginine (42%). The diversity of these responses of cortical and medullary blood flow to i.v. infusions of vasoconstrictors provides further evidence for physiological roles of circulating and local hormones in the differential regulation of regional kidney blood flow.
Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans
Authors: Ide  , Boushel  , Sørensen  , Fernandes  , Cai  , Pott  , Secher
Published: March 2003

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA Vmean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA Vmean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg−1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA Vmean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA Vmean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s−1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min−1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min−1) and ΔMCA Vmean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s−1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA Vmean (10.2 ± 2.5 cm s−1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.
Fluid balance in patients with chronic renal failure assessed with N‐terminal proatrial natriuretic peptide, atrial natriuretic peptide and ultrasonography
Authors: Metry G. , Hall C. , Wikström B. , Källskog V. , Hansell P. , Danielson B.
Published: March 2003

The N‐terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre‐dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N‐terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre‐dialysis patients venous blood samples were taken during rest to measure plasma N‐terminal proANP and ANP and serum creatinine. Normal values for N‐terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N‐terminal proANP and ANP in healthy volunteers were 328 ± 92 and 11.4.0 ± 3.1 p M L−1, respectively. In pre‐dialysis patients, serum creatinine ranged from 110 to 447 μM L−1 and was significantly correlated to plasma N‐terminal proANP (r=0.60, P < 0.05) but not to ANP. This may indicate that N‐terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N‐terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N‐terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N‐terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N‐terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.
Skeletal muscle training in chronic heart failure
Authors: Piepoli M. F. , Scott A. C. , Capucci A. , Coats A. J. S.
Published: March 2003

Patients with heart failure are limited in their ability to tolerate exercise. Recent research has suggested that this limitation cannot be entirely attributed to cardiac or lung impairment but rather that changes in peripheral muscles may play an important role. There are objective similarities between heart failure and muscular deconditioning. Deficiencies in peripheral blood flow and skeletal muscle function, morphology, metabolism and function are present in both conditions. Moreover, an exaggerated activity of the receptors sensitive to exercise‐derived metabolic signals (muscle ergoreceptors and peripheral and central chemoreceptors) leads to early and profound exercise‐induced fatigue and dyspnoea. These muscle afferents contribute to the ventilatory, haemodynamic and autonomic responses to exercise both in physiological and pathological conditions, including chronic heart failure. Against this background, a skeletal muscle origin of symptoms in heart failure has been proposed. The protective effects of physical training have been described in many recent studies: training improves ventilatory control, skeletal muscle metabolism and autonomic nervous system activity. The exercise training appears to induce its beneficial effects on skeletal muscle both directly (on muscle function, histological and biochemical features) and indirectly (by reducing the activation of the muscle afferents). The metabolic mediators of these muscle afferents may become a potential target in the future therapy of heart failure symptoms.
Eccentric exercise‐induced injuries to contractile and cytoskeletal muscle fibre components
Authors: Fridén J. , Lieber R. L.
Published: March 2003

Exercise involving lengthening of an activated muscle can cause injury. Recent reports documented the mechanics of exercise‐induced muscle injury as well as physiological and cellular events and manifestations of injury. Loss of the cytoskeletal protein desmin and loss of cellular integrity as evidenced by sarcolemmal damage occur early during heavy eccentric exercise. These studies indicate that the earliest events in muscle injury are mechanical in nature, while later events indicate that it may be more appropriate to conclude that intense exercise initiates a muscle remodeling process. We conclude that muscle injury after eccentric exercise is differently severe in muscles with different architecture, is fibre type‐specific, primarily because of fibre strain in the acute phase, and is exacerbated by inflammation after the initial injury.
Inactivity and muscle: effect of resistance training during bed rest on muscle size in the lower limb
Authors: Akima H. , Kubo K. , Imai M. , Kanehisa H. , Suzuki Y. , Gunji A. , Fukunaga T.
Published: March 2003

The present study aimed to investigate the effect of dynamic leg press training on the physiological cross‐sectional areas (PCSAs) of human lower limb muscles during 20 days of 6° head‐down tilt bed rest. Five healthy men comprised the resistance training group (BR‐Tr) and data from two previous studies were used to derive a 10‐man control group (BR‐Cont). The BR‐Tr performed two sessions (morning and afternoon session) of dynamic leg press action including knee extension and plantar flexion daily for the bed rest period: (1) three sets of 10 repetitions at 90% of maximum load and (2) 40% of maximum load to exhaustion. The PCSAs of the knee extensor (KE), knee flexor (KF), plantar flexor (PF), and dorsiflexor muscle groups were estimated using serial axial magnetic resonance (MR) images of the right‐thigh and leg. After the bed rest period, the BR‐Tr showed a significant increase in the PCSA of the KE. Although PCSA of the KF in two groups significantly decreased after bed rest, percentage of change in PCSA of the biceps femoris (long head) and semitendinosus muscles in the BR‐Tr, which occupied approximately 70% of the KF, was significantly higher than those in the BR‐Cont. Both the BR‐Tr and BR‐Cont groups showed significant decreases in the PCSA of PF with similar magnitude of 11.6% (P < 0.001) and 11.9% (P < 0.001), respectively. These results suggest that dynamic leg press training during bed rest can prevent deteriorating of the KE and a part of KF, but not the calf muscles.
Contribution of Na+/Ca2+ exchanger to the regulation of myogenic tone in isolated rat small arteries
Authors: Horiguchi S. , Watanabe J. , Kato H. , Baba S. , Shinozaki T. , Miura M. , Fukuchi M. , Kagaya Y. , Shirato K.
Published: March 2003

The contribution of the Na+/Ca2+ exchanger to the myogenic vascular tone was examined in rat isolated skeletal muscle small arteries (ASK) with pronounced myogenic tone and mesenteric small arteries (AMS) with little myogenic tone. Myogenic tone was assessed by the vascular inner diameter at transmural pressures of 40 and 100 mmHg. To depress the Na+/Ca2+ exchanger, the extracellular Na+ concentration ([Na+]o) was lowered from 143 to 1.2 mM by substituting choline‐Cl for NaCl. The ASK developed significant myogenic tone and constricted further in low [Na+]o. Nifedipine (1 μM) reduced both myogenic tone and low [Na+]o‐induced contraction. Because the membrane potential of ASK was not changed by low [Na+]o (–35 ± 2 mV at 143 mM [Na+]o, −37 ± 3 mV at 1.2 mM [Na+]o), depolarization‐induced Ca2+ influx was not a cause of the low [Na+]o‐induced contraction. The AMS did not develop significant myogenic tone. Although low [Na+]o also constricted AMS, the magnitude of constriction was significantly weaker than that in ASK (17 ± 4 vs. 47 ± 6%, P < 0.01, at 58 mM Na+). With Bay K 8644, AMS developed myogenic tone, and low [Na+]o‐induced constriction was significantly increased. In conclusion, Na+/Ca2+ exchanger may play an important role in regulating myogenic tone, likely via mediating Ca2+‐extrusion.
Genetic manipulation of the renin–angiotensin system in the kidney
Authors: Sigmund C. D.
Published: March 2003

Over the past 5 years, genetic manipulation has revolutionized the way we examine physiological processes by providing a targeted specificity that was not possible previously. The application of transgenesis and gene targeting has been applied to numerous physiological pathways; and both will remain important tools as we reach the completion of the human genome project and begin to assess the function of newly identified genes. The renin–angiotensin system (RAS) has been the target of numerous transgenic and gene targeting studies designed to help uncover its role in cardiovascular regulation and organ development. Each gene of the system has now been both over‐expressed and knocked out. It will be discussed as to how new advances in tissue‐specific gene targeting by both over‐expression and gene ablation can be used as powerful tools to dissect the role of the RAS in individual tissues.
Local gene delivery to the vessel wall
Authors: Smith R. C. , Walsh K.
Published: March 2003

This review will provide an overview of delivery strategies that are being evaluated for vascular gene therapy. We will limit our discussion to those studies that have been demonstrated, utilizing in vivo model systems, to limit post‐interventional restenosis. We also discuss the efficacy of the vectors and methods currently being used to transfer genetic material to the vessel wall. The efficiency of these techniques is a critical issue for the successful application of gene therapy.
Live high:train low increases muscle buffer capacity and submaximal cycling efficiency
Authors: Gore C. J. , Hahn A. G. , Aughey R. J. , Martin D. T. , Ashenden M. J. , Clark S. A. , Garnham A. P. , Roberts A. D. , Slater G. J. , Mckenna M. J.
Published: March 2003

This study investigated whether hypoxic exposure increased muscle buffer capacity (βm) and mechanical efficiency during exercise in male athletes. A control (CON, n=7) and a live high:train low group (LHTL, n=6) trained at near sea level (600 m), with the LHTL group sleeping for 23 nights in simulated moderate altitude (3000 m). Whole body oxygen consumption (V˙O2) was measured under normoxia before, during and after 23 nights of sleeping in hypoxia, during cycle ergometry comprising 4×4‐min submaximal stages, 2‐min at 5.6 ± 0.4 W kg–1, and 2‐min ‘all‐out’ to determine total work and V˙O2peak. A vastus lateralis muscle biopsy was taken at rest and after a standardized 2‐min 5.6 ± 0.4 W kg–1 bout, before and after LHTL, and analysed for βm and metabolites. After LHTL, βm was increased (18%, P < 0.05). Although work was maintained, V˙O2peak fell after LHTL (7%, P < 0.05). Submaximal V˙O2 was reduced (4.4%, P < 0.05) and efficiency improved (0.8%, P < 0.05) after LHTL probably because of a shift in fuel utilization. This is the first study to show that hypoxic exposure, per se, increases muscle buffer capacity. Further, reduced V˙O2 during normoxic exercise after LHTL suggests that improved exercise efficiency is a fundamental adaptation to LHTL.
Polylysine binding to unphosphorylated smooth muscle myosin enhances formation and stabilizes myosin filaments in vitro
Authors: SZYMANSKI P. T. , FERGUSON D. G. , PAUL R. J.
Published: March 2003

Previously, we demonstrated that positively charged polylysine, our model for biological polyamines, activates the Mg2+ ATPase activity of unphosphorylated smooth muscle myosin and shifts the myosin conformation from the folded 10S to linear 6S form. These effects of polylysine were reversed by the oppositely charged heparin (Szymanski et al. (1993) Am J Physiol265, C379). In the present report, we provide further information on polylysine binding to smooth muscle myosin, and test the hypothesis that polylysine binding to unphosphorylated myosin involves filament formation. To relate the effects of polylysine on contractility in smooth muscle to physiologically relevant material, we investigated the ability of naturally occurring positively charged polyamines, histones, cadaverine, putrescine and spermidine to activate the Mg2+ ATPase activity of unphosphorylated smooth muscle myosin. Our data show that polylysine binding to individual unphosphorylated myosin molecules stimulates formation of myosin filaments. Polylysine also interacts with myosin filaments, causing enhancement of their size and the numbers, and this could be reversed by heparin. Polylysine binding to myosin filaments made them more resistant to disassembly by high salt concentrations (KCl) or ATP. Naturally occurring polyamines in millimolar concentrations activate the Mg2+ ATPase activity of unphosphorylated smooth muscle myosin. We suggest that the electrostatic interactions between naturally occurring positively charged polyamines and unphosphorylated smooth muscle myosin may play a role in stabilization of thick filament structurein situ.
Gene expression of colony‐stimulating factors and stem cell factor after myocardial infarction in the mouse
Authors: WOLDBAEK P. R. , HOEN I. B. , CHRISTENSEN G. , TØNNESSEN T.
Published: March 2003

Recent studies have suggested that cytokines such as macrophage colony‐stimulating factor (M‐CSF) might be involved in the pathogenesis of ischaemic heart disease. Macrophage colony‐stimulating factor, granulocyte‐colony stimulating factor (G‐CSF), granulocyte‐macrophage‐colony stimulating factor (GM‐CSF), stem cell factor (SCF), interleukin‐3 (IL‐3) and interleukin‐7 (IL‐7) are potent cytokines belonging to the same structual class that may affect function, growth and apoptosis both in the heart and other organs. The aims of the present study were to characterize a post‐infarction model in the mouse and to examine mRNA expression of M‐CSF, GM‐CSF, SCF, IL‐3 and IL‐7 during the development of heart failure. Myocardial infarction (MI) was induced in mice by ligation of the left coronary artery. Average infarct size was 40% and the mice developed myocardial hypertrophy and pulmonary oedema. Ribonuclease (RNAase) protection assays showed abundant cardiac expression of M‐CSF and SCF. After MI, we measured down‐regulation of cytokine mRNA expression in the heart (M‐CSF, SCF), lung (M‐CSF), liver (M‐CSF) and spleen (M‐CSF) compared with sham. Cardiac G‐CSF, GM‐CSF and IL‐7 mRNAs were not detected. In conclusion, abundant cardiac gene expression of M‐CSF and SCF was found. In our mouse model of MI, M‐CSF and SCF were down‐regulated in the heart and several other organs suggesting specific roles for these cytokines during development of ischaemic heart failure.
Central osmotic regulation of sympathetic nerve activity
Authors: Toney G. M. , Chen Q. H. , Cato M. J. , Stocker S. D.
Published: March 2003

AbstractAim: In this review, we will focus on the central neural mechanisms that couple osmotic perturbations to changes in sympathetic nerve discharge, and the possible impact these actions have in cardiovascular diseases such as arterial hypertension and congestive heart failure.

Results: Changes in extracellular fluid osmolality lead to specific regulatory responses in defence of body fluid and cardiovascular homeostasis. Systemic hyperosmolality is well known to stimulate thirst and the release of antidiuretic hormone. These responses are largely due to osmosensing neurones in the forebrain lamina terminalis and hypothalamus and are critical elements in a control system that operates to restore body fluid osmolality. An equally important, but less characterized, target of central osmoregulatory processes is the sympathetic nervous system.

Conclusion: Understanding the neurobiology of sympathetic responses to changes in osmolality has important implications for body fluid and cardiovascular physiology. By stabilizing osmolality, vascular volume is preserved and thereby relatively normal levels of cardiac output and arterial pressure are maintained.
Strength and power changes of the human plantar flexors and knee extensors in response to resistance training in old age
Authors: Ferri A. , Scaglioni G. , Pousson M. , Capodaglio P. , Van Hoecke J. , Narici M. V.
Published: March 2003

Abstract Aim:  The aim of the present study was to assess and compare the improvements of muscle strength and power induced by a 16‐week resistive programme in a population of 16 older men aged 65–81 years.

Methods:  Training was performed three times per week at an intensity of 80% of one repetition maximum (1RM) and consisted of both calf raise and leg press exercises. Before‐, during‐ and after‐training, maximum isometric and isokinetic torques, maximum power, 1RM, muscle cross‐sectional area (CSA) and electromyographic activity (EMG) of the plantar flexors (PF) and knee extensors (KE) were examined.

Results:  For the KE and PF, respectively, training resulted in a 29.9 ± 4.4% (mean ± SE) and 21.6 ± 5.4% increase in 1RM (P < 0.001–0.01), a 19.4 ± 4.3 and 12.4 ± 4.7% (P < 0.001–0.05) increase in maximum isometric torque, and a 24.1 ± 6.3 and 33.1 ± 10.9% (P < 0.05) increase in maximum muscle power, calculated from torque–angular velocity curves. The large increase in torque and power was partly accounted by a significant increase in the CSA of the PF (5.0 ± 0.7%) and KE (7.4 ± 0.7%), while no significant changes in integrated EMG activity of vastus lateralis and soleus muscles, and in extrapolated maximum shortening velocity were found. After training, a significant increase in torque/CSA (10.3 ± 4%, P < 0.05) was found for the KE but not for the PF.

Conclusion:  Hence, hypertrophy cannot alone justify the increase in torque, and other factors, such as an increase in individual fibre‐specific tension (in the case of KE), a decrease in antagonist muscles' coactivation, an improved co‐ordination and an increased neural drive of the other heads of quadriceps may have contributed to the increments in strength. The significant increase in muscle power seems particularly noteworthy with respect to daily activities involving the displacement of the body over time, namely, the generation of muscle power.
Amazing chloride channels: an overview
Authors: Nilius B. , Droogmans G.
Published: March 2003

Aim:
This review describes molecular and functional properties of the following Cl
–
channels: the ClC family of voltage‐dependent Cl
–
channels, the cAMP‐activated transmembrane conductance regulator (CFTR), Ca
2+
activated Cl
–
channels (CaCC) and volume‐regulated anion channels (VRAC). If structural data are available, their relationship with the function of Cl
–
channels will be discussed. We also describe shortly some recently discovered channels, including high conductance Cl
–
channels and the family of bestrophins. We illustrate the growing physiological importance of these channels in the plasma membrane and in intracellular membranes, including their involvement in transepithelial transport, pH regulation of intracellular organelles, regulation of excitability and volume regulation. Finally, we discuss the role of Cl
– channels in various diseases and describe the pathological phenotypes observed in knockout mice models.
Sympathetic control of white adipose tissue in lean and obese humans
Authors: Dodt C. , Lönnroth P. , Wellhöner J. P. , Fehm H. L. , Elam M.
Published: March 2003

Aim:  To induce lipolysis, catecholamines could reach the adipocyte via the blood stream after being released from the adrenal medulla or, alternatively, via neuronal release in the vicinity of the fat cell. Sympatho‐neuronal effects on fat tissue lipolysis have been demonstrated in experimental animal models. However, the role of sympathetic nerves in the control of lipolysis in human white adipose tissue, which is sparsely innervated, has not been clarified.

Conclusion:  The present review summarizes evidence for a direct neuronal influence on lipolysis in humans.
Chemoreflexes – physiology and clinical implications
Authors: Kara T. , Narkiewicz K. , Somers V. K.
Published: March 2003

The chemoreflexes are important modulators of sympathetic activation. The peripheral chemoreceptors located in the carotid bodies respond primarily to hypoxaemia. Central chemoreceptors located in the region of the brainstem respond to hypercapnia. Activation of either the hypoxic or hypercapnic chemoreflex elicits both hyperventilation and sympathetic activation. During apnoea, when the inhibitory influence of stretch of the pulmonary afferents is eliminated, there is a potentiation of the sympathetic response to both hypoxia and hypercapnia. This inhibitory influence of the pulmonary afferents is more marked on the sympathetic response to peripheral compared with central chemoreceptor activation. The arterial baroreflexes also have a powerful inhibitory influence on the chemoreflexes. This inhibition is again more marked with respect to the peripheral compared with central chemoreflexes.

In patients with hypertension, there is a marked increase in the sympathetic and ventilatory response to hypoxaemia. During apnoea, with elimination of the inhibitory influence of breathing, the sympathetic response in untreated mild hypertensive patients is strikingly greater than that seen in matched normotensive controls. This potentiated peripheral chemoreflex sensitivity in hypertension may be explained in part by impaired baroreflex function in these patients. Enhanced peripheral chemoreflex sensitivity is also evident in patients with obstructive sleep apnoea. This peripheral chemoreflex enhancement is not explained by obesity, as obese individuals have a selective potentiation of the central chemoreceptors with peripheral chemoreflex responses similar to those seen in lean controls. Increased sensitivity to hypoxaemia has important implications in patients with obstructive sleep apnoea who experience repetitive and severe hypoxaemic stress. Tonic activation of the chemoreflex may also contribute to the high levels of sympathetic activity evident even during normoxic daytime wakefulness in sleep apnoea patients. Administration of 100% oxygen in patients with sleep apnoea results in reductions in heart rate, blood pressure and central sympathetic outflow.

In patients with heart failure, the central chemoreflex response to hypercapnia is markedly and selectively enhanced. This increased central chemoreflex sensitivity may contribute to the development of central sleep apnoea in heart failure patients. Administration of 100% oxygen does not lower sympathetic activity in patients with heart failure, providing further evidence against any peripheral chemoreflex potentiation.

The peripheral and central chemoreflexes have powerful effects on sympathetic activity in both health and disease and may contribute importantly to disease pathophysiology, particularly in conditions such as hypertension, obstructive sleep apnoea and heart failure.
Growth features of Acacia tortilis and Acacia xanthophloea seedlings and their response to cyclic soil drought stress
Authors: Otieno D. O. , Kinyamario J. I. , Omenda T. O.
Published: March 2003

Seedlings of Acacia tortilis (Forsk) Hyne and Acacia xanthophloea Benth. were raised under controlled glasshouse conditions. Control plants were watered daily while other treatments involved withholding water for 2, 4 and 6 days with 1‐day rehydration to container capacity.

Compared to A. tortilis, A. xanthophloea seedlings showed higher leaf area, relative growth rates and total dry weight production under adequate water supply conditions. However, with increased water stress, A. xanthophloea seedlings could not alter their pattern of carbon allocation, retaining their root : shoot (r : s) ratio of about 0.5. By comparison, A. tortilis seedlings shifted carbon allocation to the roots, leading to a r : s ratio of 1.5 in water‐stressed seedlings, compared to 0.5 in the control plants.

The ability of A. tortilis to reallocate carbon to the roots away from the shoots and to actually increase root growth compared to A. xanthophloea was a dehydration postponement strategy that may be important in species survival during drought.
Vegetation dynamics of coastal sand dunes near Malindi, Kenya
Authors: Musila W. M. , Kinyamario J. I. , Jungerius P. D.
Published: March 2003

This study describes the composition, structure and distribution of coastal dune vegetation near Malindi, Kenya. The vegetation was made up of 156 plant species. Sixty families were recorded with Gramineae (seventeen species) and Papilionaceae (sixteen species) being the most widely represented. Fifteen plant communities were described in the different geomorphologic units. The plant communities exhibited a distinct zonal distribution. Halopyrum mucronatum and Ipomoea pes‐caprae plant communities were common in the unstable geomorphologic units. Cordia somaliensis and Pluchea dioscoridis plant communities were common in the more stable geomorphologic units. Most of the plants in the more stable geomorphologic units were shrubs and trees. Succulent herbs were identified in the slacks and the drowned valley, which have moist and damp environments.
Changes in miombo woodland cover in and around Sengwa Wildlife Research Area, Zimbabwe, in relation to elephants and fire
Authors: Mapaure Isaac N. , Campbell Bruce M.
Published: March 2003

One of the consequences of impacts of elephants and fire on woodlands is a change in woody cover, which often results in major challenges for wildlife managers. Changes in miombo woodland cover in and around Sengwa Wildlife Research Area (SWRA) between 1958 and 1996 were quantified by analyzing aerial photographs. Woody cover in SWRA decreazed from 95.2% in 1958 to 68.2% in 1996, with a lowest mean of 62.9% in 1983. The annual absolute rate of woody cover change in SWRA increazed from −1.1% per annum between 1958 and 1964 to a recovery of 1.6% per annum between 1993 and 1996, while the annual relative rate increazed from −1.1% per annum between 1958 and 1964 to 3.3% per annum between 1993 and 1996. There was a strong negative correlation between elephant densities and woody cover in SWRA, suggesting that loss of woody cover was mainly due to elephants. Woodland recovery after 1983 was due to reductions in elephant populations through legal and illegal off‐take and reductions in fire frequency. Surrounding areas experienced less woody cover losses than SWRA, mainly due to tree removal by locals whose densities increazed after the eradication of tsetse fly in the 1970s.
Diet of Mackinder's eagle owl Bubo capensis mackinderi in the alpine zone of Mount Kenya
Authors: Rödel Heiko G. , Scholze Wolfgang W. A. , Kock Dieter
Published: March 2003

The diet of Bubo capensis mackinderi Sharpe in the alpine zone of Mt. Kenya was studied by analysing pellets collected from nesting and roosting sites in four different valleys. Overall, mammals comprised 97.4% of prey individuals and 98.9% of the ingested biomass. Rodents, mainly groove‐toothed rats, were the owl's staple food in all four valleys, but rock hyrax, insectivores and birds were also consumed. Proportions of rock hyrax, rodents and insectivores did not differ between the valleys. Total dietary composition in the different valleys showed a high degree of overlap in proportions of main prey types averaging 93.2% in percentage of occurrence and 85.0% in percentage of biomass.
Increased expression of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats
Authors: Fujiwara Y. , Higuchi K. , Takashima T. , Hamaguchi M. , Watanabe T. , Tominaga K. , Oshitani N. , Matsumoto T. , Arakawa T.
Published: March 2003

Background:

Epidermal growth factor (EGF), which binds to EGF receptors (EGF‐R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF‐R expression is present and confined to the basal layer.

Aim:

To examine histological changes in and dynamics of EGF‐R expression during healing after acid reflux oesophagitis in a rat model.

Methods:

Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF‐R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF‐R mRNA and protein by RT–PCR and Western blotting or immunohistochemistry.

Results:

Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 ± 3.09 μm in controls to 142.73 ± 11.59 μm (P < 0.001) in ligated rats, as well as elongation of papillae and basal cell hyperplasia. The number of BrdU‐positive cells among basal cells on day 14 was significantly increased from 7.1 ± 0.8/field in controls to 30.9 ± 3.0/field in ligated rats. Expression of EGF‐R mRNA and protein was significantly increased on day 14 and most basal cells were immunohistochemically positive in both BrdU and EGF‐R staining.

Conclusion:

Acid reflux‐induced oesophageal injury caused basal cell hyperplasia with an increase in cell proliferation and EGF‐R expression. Activation of EGF‐R gene and protein in response to acid reflux‐induced injury may facilitate mucosal healing. These results suggest that epidermal growth factor receptors play a crucial role in healing after acid reflux oesophagitis in rats.