bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental And Genetic Determinants Of Intima–Media Thickness Of The Carotid Artery
Authors: Zannad F , Sass C , Visvikis S 
Published: March 2003

SUMMARY1. The aim of the present study was to investigate carotid intima–media thickness (CIMT) in relation to anthropometric, environmental and genetic factors, as well as cholesterol and blood pressure levels.2. The study sample was composed of 89 families, with no documented cardiovascular disease, consisting of 369 subjects (aged from 10 to 54 years) from the Stanislas cohort.3. Carotid intima–media thickness was measured by B‐mode ultrasonography. Fifteen genetic markers, including genes involved in lipid metabolism, the regulation of blood pressure, thrombosis, platelet function and endothelial cell adhesion, were studied by multiplex assay.4. The effects of gender, age, smoking, alcohol, body mass index, cholesterol, blood pressure and genetic factors were studied using ANOVA and bivariate and regression analyses.5. Segregation analysis was also performed to estimate the contribution of genetic and environmental factors to CIMT variability.6. Carotid intima–media thickness values were not affected by age or by gender up to 18 years of age. Thereafter, CIMT values increased sharply in men and remained significantly higher than in women.7. Approximately 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in the apolipoprotein CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase and fibrinogen genes were observed and explained approximately 20% of CIMT variation in men.8. In women, none of the studied polymorphisms was associated with CIMT variation.9. Our study gives new perspectives for understanding CIMT variability in healthy middle‐aged subjects.
Interactions Between Sodium And Angiotensin
Authors: Morgan Trefor 
Published: March 2003

SUMMARY1. Increased sodium intake causes decreased formation of angiotensin (Ang) II and increased AngII causes increased Na+ retention.2. Increased sodium intake and increased AngII causes cardiac hypertrophy, but decreased sodium intake regresses cardiac hypertrophy despite high AngII levels. Likewise, decreased Na+ and blockers of the renin–angiotensin system (RAS) in neonatal rats have similar effects on subsequent blood pressure development.3. Cardiac hypertrophy due to renal hypertension does not regress when the RAS is blocked and rats are on a high salt intake. Likewise, sodium restriction alone does not cause regression; combination of reduced NaCl intake and RAS blockade is required.4. High doses of perindopril and losartan in combination cause a syndrome in rats on 0.2% NaCl that leads to profound hypotension, polyuria, renal impairment and involution of the heart and death. This is reversed or prevented by a high (4%) NaCl intake, which also prevents the plasma angiotensinogen depletion that occurs with combined blockade on 0.2% NaCl intake.5. Intake of NaCl and AngII interact at many levels. It is postulated that there is an important interaction at the cellular level that can explain the above events.
Genetic Influences On Cardiovascular Responses To An Acoustic Startle Stimulus In Rats
Authors: Baudrie Véronique , Laude Dominique , Chaouloff Francis , Elghozi Jean‐Luc 
Published: March 2003

SUMMARY1. The aim of the present study was to assess the cardiovascular differences among five inbred rat strains (n = 16 per strain), including spontaneously hypertensive rats (SHR), Wistar Kyoto (WKY) rats, Wistar Furth (WF) rats, Fischer (F344) rats and Lewis (Lew) rats and the usual outbred Wistar (W) rat strain (n = 25).2. These strains were compared under resting conditions for blood pressure (BP) and heart rate (HR) levels and for their baroreceptor–HR reflex sensitivity. In addition, their responses to an acoustic startle stimulus were measured.3. A consistent rise in BP was observed among the groups as a result of the noise stimulus. This rise in systolic BP (SBP) averaged (±SEM) 37 ± 2 mmHg in the SHR and 34 ± 4 mmHg in F344 rats, while the response was only 23 ± 3 mmHg in WKY rats. Pulse pressure (PP) was increased following noise in all groups. The delay for the BP response for all groups combined was 1.6 ± 0.1 s.4. Most animals had minimal HR variations, except F344 rats, responding with a 42 ± 13 b.p.m. decrease 3.0 s after the stimulus (i.e. 1.3 s after the maximal 34 ± 4 mmHg SBP rise).5. The highest SBP (160 ± 3 mmHg) and diastolic BP (104 ± 3 mmHg) were observed in inbred SHR. Other groups were normotensive. Resting PP was elevated for SHR (56 ± 2 mmHg) compared with the other groups (40 ± 2 mmHg). The highest HR was found in F344 and WF rats, with 389 ± 11 and 372 ± 7 b.p.m., respectively. The lowest HR was observed in SHR and Lewis rats, with 335 ± 7 and 323 ± 7 b.p.m., respectively. The least sensitive baroreflex function was observed in SHR (0.8 ± 0.1 b.p.m./mmHg) compared with the other strains (1.4 ± 0.2 b.p.m./mmHg).6. The present study confirms the importance of genetic factors on the cardiovascular responses of rats to a noise startle stimulus. Two inbred normotensive rat strains, namely F344 and WKY rats, which exhibit a substantial difference in pressor response to noise, may be used to unravel the mechanisms of sympathetic activation.
The Adenine Nucleotide Translocator: Regulation And Function During Myocardial Development And Hypertrophy
Authors: Portman Michael A 
Published: March 2003

SUMMARY1. The present review focuses on the adenine nucleotide translocator (ANT), which facilitates exchange of cytosolic ADP for mitochondrial ATP. This protein serves a central role in regulating cellular oxidative capacity.2. The ANT, a nuclear‐encoded mitochondrial protein, is developmentally regulated and, thus, accumulates within the mitochondrial membrane during maturation.3. Accumulation of ANT parallels changes in kinetics of myocardial respiration determined from 31P magnetic resonance spectroscopy studies.4. Thyroid hormone modulates developmental transitions in ANT content, as well as respiratory control patterns. These transitions are linked to quantitative ANT changes, not to alterations in functionality at individual exchanger sites.5. Developmental programming for ANT and parallel alterations in oxidative phosphorylation kinetics are relevant to the heart, which exhibits remodelling in response to pathological processes. Maladaptive hearts exhibiting ANT deficits demonstrate ADP‐dependent respiratory kinetics similar to the newborn heart. Thus, ANT deficits and alterations in mitochondrial respiratory function may contribute to the pathogenesis of myocardial remodelling and heart failure.
Gaba In The Control Of Sympathetic Preganglionic Neurons
Authors: Llewellyn‐Smith Ida J 
Published: March 2003

SUMMARY1. Amino acid neurotransmitters are critical for controlling the activity of most central neurons, including sympathetic preganglionic neurons (SPN), the spinal cord neurons involved in controlling blood pressure and other autonomic functions.2. In studies reviewed here, SPN were identified either by retrograde tracing from a peripheral target (superior cervical ganglion or adrenal medulla) or by detection of immunoreactivity for choline acetyltransferase (ChAT), the acetylcholine‐synthesizing enzyme that is a marker for all SPN, in intact or completely transected rat spinal cord.3. Postembedding immunogold labelling on ultrathin sections was then used to detect GABA and sometimes glutamate in nerve terminals on SPN or near them in the neuropil of the lateral horn.4. In some cases, the terminals were prelabelled to show an anterograde tracer or immunoreactivity for ChAT or neuropeptide Y.5. This anatomical work has provided information that is helpful in understanding how SPN are influenced by their GABAergic innervation.6. Immunogold studies showed that the proportion of input provided by GABAergic terminals varies between different groups of SPN. For some groups, this input may be preferentially targeted to cell bodies.7. Anterograde tracing demonstrated that supraspinal as well as intraspinal GABAergic neurons innervate SPN and investigations on completely transected cord suggested that supraspinal neurons may provide a surprisingly large proportion of the GABAergic terminals that contact SPN.8. The double‐labelling studies in which other amino acids, ChAT or neuropeptide Y were localized along with GABA indicate that GABAergic terminals contain other neurochemicals that could modulate the actions of GABA, depending on the complement of receptors that are present pre‐ and post‐synaptically.9. Taken together, these data indicate that GABAergic transmission to SPN may be much more complicated than suggested by the currently available electrophysiological studies.
Evidence For The Existence Of A Constitutive Nitric Oxide Synthase In Vascular Smooth Muscle
Authors: Cheah LS , Gwee MCE , Das R , Ballard H , Yang YF , Daniel EE , Kwan CY 
Published: March 2003

SUMMARY1. We have identified a neuronal nitric oxide synthase (NOS)‐like constitutive form of NOS in vascular smooth muscle (VSM) using a functional contractility approach as well as immunohistochemical methods.2. NG‐Nitro‐L‐arginine methyl ester, NG‐monomethyl‐L‐ arginine and NG‐nitro‐L‐arginine (L‐NOARG), the competitive inhibitors of NOS, inhibited Mg2+‐induced relaxation of de‐endothelialized rat aorta precontracted with phenylephrine (PE). This Mg2+ relaxation of VSM was not affected by inhibitors of inducible NOS.3. Electrical field stimulation (EFS; 30–70 Hz) caused relaxation of rat aorta in the presence of tetrodotoxin (therefore not a neurogenic effect) and this EFS relaxation was effectively inhibited by L‐NOARG, oxyhemoglobin and methylene blue.4. Immunohistochemical studies of dog saphenous vein using antibodies raised against neuronal NOS indicated prominent staining along the plasmalemma in a punctate pattern similar to the distribution of antibodies against caveolin‐1, a major constituent of the plasmalemmal caveolae.5. We propose that a constitutive NOS of non‐endothelial, non‐neuronal origin is present in a special caveolae domain of VSM cell membranes and could be activated by an ionic mechanism yet to be characterized.
Heterogeneous Distribution Of β‐Adrenoceptors and Muscarinic Receptors In The Sinoatrial Node And Right Atrium Of The Dog
Authors: Kurogouchi Fumio , Nakane Tokio , Furukawa Yasuyuki , Hirose Masamichi , Inada Yoichi , Chiba Shigetoshi 
Published: March 2003

SUMMARY1. The pacemaker site is known to shift away from the sinoatrial (SA) node in response to autonomic stimuli.2. To test whether the shifting of the impulse‐initiation site that occurs during autonomic nerve stimulation can be explained by the spatial distributions of β‐adrenoceptor and muscarinic receptors, we obtained densities (Bmax) and dissociation constants (Kd) for these receptors in three regions along the sulcus terminalis (the SA node itself and regions superior and inferior to it) and a region of the right atrial appendage in the dog.3. The Bmax values for [125I]‐iodocyanopindolol binding to β‐adrenoceptors were not different among the four regions. The Bmax value for [3H]‐quinuclidinyl benzilate binding to muscarinic receptors was significantly higher in the SA node area than in any other region (P < 0.01), although there was no difference among the other three regions.4. For each receptor, Kd values were similar among the four regions.5. These results suggest that spatial variations in the densities of β‐adrenoceptors and muscarinic receptors are not important for shifting the impulse‐initiation site and that other factors, such as non‐uniform innervation by autonomic nerve fibres, may be mainly responsible for the pacemaker shift induced by autonomic nerve stimulation.
Effect Of Glycerol On Endothelium‐Derived Factors In The Vasculature Of The Rabbit Kidney
Authors: Sipahi Emine Y , Keskil Zuhal A , Erdinç Meral , Nergis Yusuf , Türker R Kazlm , Ercan Z Sevim 
Published: March 2003

SUMMARY1. In the present study, endothelium‐derived relaxing factor (EDRF/nitric oxide (NO)), conversion of big endothelin (ET)‐1 to endothelin‐1 (ET‐1) and the role of reactive oxygen species were investigated in kidneys isolated from glycerol (GLY)‐pretreated rabbits.2. Acetylcholine (ACh)‐induced vasodilation that is due to the release of EDRF/NO is significantly decreased, whereas big ET‐1‐induced vasoconstriction was increased in kidneys isolated from GLY‐pretreated rabbits.3. Pretreatment of rabbits with the xanthine oxidase inhibitor allopurinol and the NO precursor L‐arginine reversed the inhibition of ACh‐induced vasodilation due to GLY and protects the kidney vasculature.4. Big ET‐1, but not ET‐1, responses were found to be significantly increased in kidneys isolated from GLY‐pretreated rabbits. This increase is attributed to the higher conversion rate of big ET‐1 to ET‐1 because the ET‐converting enzyme (ECE) inhibitor phosphoramidon, at a concentration of 10–6 mol/L, causes an inhibition in the response to big ET‐1 by 52.6% in normal kidneys, whereas this inhibition with the same concentration of phosphoramidon was found to be significantly decreased in kidneys isolated from GLY‐pretreated rabbits.5. The non‐selective NO synthase inhibitor NG‐nitro‐L‐ arginine methyl ester (L‐NAME) caused a significant potentiation in the vasoconstrictor response to ET‐1 in normal isolated perfused rabbit kidneys. However, L‐NAME did not alter the responses to ET‐1 in GLY‐pretreated kidneys.6. These results indicate that accumulation of reactive oxygen species causes an inhibition in NO bioavailability. Increased conversion of big ET‐1 to ET‐1 may also contribute to the mechanism of vascular damage due to GLY.
Cyclosporine A protects against apoptosis in ischaemic/reperfused rat kidneys
Authors: Zhu Tongyu , Au‐Yeung Kathy KW , Siow Yaw L , Wang Guoping , O Karmin 
Published: March 2003

Summary1. Renal ischaemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allografts. Cyclosporine A (CsA) has been used as an immunosuppressive agent in organ transplantation. In the present study, the effect of CsA on ischaemia/reperfusion‐induced apoptosis in the kidney was investigated.2. Ischaemia/reperfusion injury caused widespread apoptosis primarily in the medulla of the kidney. At 1.5 mg/kg per day, CsA significantly reduced the number of apoptotic cells in rat kidney after ischaemia/reperfusion injury.3. Low‐dose CsA treatment did not affect the levels of creatinine in the serum of rats after ischaemia/reperfusion injury.
Ageing blunts the effects of nitric oxide on myocardial O2 consumption
Authors: Weiss Harvey R , Lazar Michael J , Tse James , Scholz Peter M 
Published: March 2003

Summary1. In the present study, we tested the hypothesis that the negative myocardial metabolic effects of nitric oxide (NO) were reduced in old hearts.2. Studies were conducted in 17 young (approximately 6 months) and 18 old (> 36 months) New Zealand anaesthetized open‐chest rabbits. Either vehicle or s‐nitroso‐N‐acetylpenicillamine (SNAP; 10−4 mol/L; a NO donor) was applied to the epicardial surface of the left ventricle. Coronary blood flow (microspheres) and artero–venous (a‐v) O2 difference (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption. Wall thickening was determined ultrasonically. Cyclic GMP and guanylyl cyclase activity were also determined. Myocardial a‐v O2 difference, flow, O2 consumption and wall thickening were comparable in young and old hearts.3. The EPI and ENDO O2 consumption of SNAP‐treated young hearts decreased significantly (> 25%) compared with vehicle (saline). However, SNAP had no significant effects on the O2 consumption of old hearts. In addition, SNAP decreased the percentage wall thickening in young (from 18.0 ± 1.7 to 13.4 ± 1.6%), but not old (from 14.5 ± 0.9 to 11.4 ± 1.6%), hearts. Basal cGMP levels in old hearts were greater (approximately 70%) than those in young hearts (15.7 ± 2.0 vs 9.0 ± 0.8 pmol/g, EPI). s‐Nitroso‐N‐acetylpenicillamine increased cGMP in EPI (13.7 ± 1.8 pmol/g) and ENDO of young, but not old (18.7 ± 2.3 pmol/g, EPI), hearts. Similar results were also obtained using another NO donor, namely sodium nitroprusside (SNP; 10−4 mol/L). Guanylyl cyclase activity was elevated in old rabbit hearts with 0.5 mmol/L SNP (131 ± 12 vs 80 ± 12 pmol/min per mg protein for old and young rabbits, respectively).4. Thus, while older hearts had similar O2 consumption and wall thickening compared with young hearts, they responded less well to NO and had significantly elevated basal levels of myocardial cGMP.
Renal function in adult rats subjected to prenatal dexamethasone*
Authors: Martins João PC , Monteiro Josélia C , Paixão Ana DO 
Published: March 2003

Summary1. Prenatal dexamethasone leads to low birth weight and compromises organogenesis, but its effects on nephrogenesis in male and female rats have not yet been investigated extensively. Reduced renal mass may be responsible for hypertension and renal haemodynamic and morphological adjustments to maintain the glomerular filtration rate (GFR). Subsequently, these compensatory mechanisms determine glomerular sclerosis and irreversible reduction in GFR. When a high‐protein diet is associated with reduced renal mass, it accelerates glomerular sclerosis and the decline in renal function. The aim of the present study was to evaluate whether rats subjected to prenatal dexamethasone and a high‐protein diet during growth present a premature decline in renal function.2. The number of nephrons and renal haemodynamics were estimated in Wistar rats fed a high‐protein diet (40% protein) after weaning in offspring of dams treated with either dexamethasone (0.1 mg/kg per day) or its vehicle (control; physiological solution, 0.1 mL/kg per day) during gestation.3. At 70 days of age, rat offspring were anaesthetized and prepared surgically for renal haemodynamic measurements.4. Mean arterial pressure (MAP), renal blood flow (RBF) and GFR were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively.5. The number of nephrons was counted using the acid‐maceration technique.6. Dexamethasone during pregnancy induced a lower weight gain in the dams (65%; P < 0.0001) and a lower birth weight in both male and female offspring (14 and 13%, respectively; P < 0.01).7. Compared with control, the number of nephrons in male rats was reduced by 13% (30 703 ± 1262 vs 26 308 ± 1305, respectively; P < 0.05), but was unaltered in female rats (23 197 ± 553 vs 24 231 ± 1009, respectively).8. Male and female rats did not show any alteration in MAP. In addition, they did not show any alteration in renal vascular resistance, RBF, filtration fraction or GFR.9. In conclusion, prenatally administered dexamethasone (0.1 mg/kg during the entire pregnancy) induced a low birth weight. The magnitude of the reduction in nephrogenesis in male offspring from mothers treated with dexamethasone was not sufficient to alter renal function (measured at 70 days), even when rats had been fed a high‐protein diet.
Extracellular Ca2+ is obligatory for ouabain‐induced potentiation of cardiac basal energy expenditure
Authors: Guild S‐J , Ward M‐L , Cooper PJ , Hanley PJ , Loiselle DS 
Published: March 2003

Summary1. The method of action of cardiac glycosides is commonly explained by the ‘pump‐inhibition hypothesis’: inhibition of the Na+/K+‐ATPase allows [Na+]i to rise, eventually reversing Na+/Ca2+ exchange. The resulting influx of Ca2+o increases [Ca2+]i, thereby activating intracellular Ca2+‐dependent ATPases and, hence, energy demand. This sequence has been presumed to occur during diastole as well as systole. However, it has been reported that dihydro‐ouabain‐induced potentiation of heat production by quiescent ventricular trabeculae persists in the absence of Ca2+o. This implies that the pump‐inhibition hypothesis is inapplicable during diastole.2. We tested this implication by: (i) measuring the rate of oxygen consumption (Vo2) of arrested guinea‐pig whole‐hearts; (ii) measuring[Ca2+]i in quiescent ventricular trabeculae; and (iii) mathematical modelling using software (Oxsoft Heart, Oxford Software, Oxford, UK) based on DiFrancesco‐Noble formalism.3. Upon induction of arrest, whole heart Vo2 fell to one‐quarter of its ‘beating’ value. Subsequent perfusion with ouabain (20 µmol/L), in the presence of Ca2+o, increased Vo2 fourfold. This increase was prevented by withholding Ca2+o. Comparable results were obtained in quiescent trabeculae: ouabain increased [Ca2+]i only if Ca2+o was present. Mathematical modelling readily simulated these experimental results.4. We conclude that influx of Ca2+o is mandatory for potentiation of cardiac basal metabolism by cardiac glycosides.
Effects of five commonly used glucocorticoids on haemangioma in vitro¶
Authors: Hasan Q , Tan ST , Xu B , Davis PF 
Published: March 2003

Summary1. High‐dose systemic or intralesional steroids are the first‐line pharmacological treatments for haemangioma. However, the mechanism of action of steroids is unknown. Using the in vitro model developed by us, the present study examined some of the effects of five commonly used glucocorticoids on haemangioma biopsies taken from two patients.2. At 12 µmol/L, triamcinolone and dexamethasone consistently exhibited capillary growth inhibition, whereas methylprednisolone displayed an inhibitory effect during the first 7 days of culture. At this concentration, inhibition of capillary growth was observed in betamethasone‐treated cultures derived from one patient but not in those derived from the other. However, hydrocortisone had a negligible effect on capillary growth.3. Transcription of various factors considered important for haemangioma development were studied by reverse transcription–polymerase chain reaction. Neither vascular endothelial growth factor nor fibroblast growth factor‐2 played a vital role in steroid‐induced inhibition of capillary growth. All glucocorticoids induced a marked decrease of interleukin (IL)‐6 transcripts.4. Capillary growth inhibition in cultures treated with all glucocorticoids, except triamcinolone, was associated with an increased transcription of clusterin/apolipoprotein J (clust/apoJ), an apoptotic gene. There was increased transcription of mitochondrial cytochrome (cyt) b in the inhibited cultures resulting from triamcinolone, dexamethasone or methylprednisolone treatment that was associated with capillary growth inhibition, suggesting an important role of mitochondria in glucocorticoid‐induced regression of haemangioma.5. Our results indicate that glucocorticoids may modulate haemangiogenesis via an upregulation of cyt b, clust/apoJ and/or IL‐6. The variable effects of different glucocorticoids on one or more of these factors may explain the interindividual variation in the in vivo response of haemangioma to the steroids.