bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects Of Nitric Oxide Synthase Inhibition And Low‐Salt Diet On Blood Pressure And Mesenteric Resistance Artery Remodelling In Genetically Hypertensive Rats
Authors: Ledingham Janet M , Laverty Richard 
Published: March 2003

SUMMARY1. Nitric oxide synthase (NOS)‐inhibited genetically hypertensive (GH) rats on normal and low‐sodium diets were additionally given valsartan or felodipine to establish whether low‐Na intake would have extra beneficial effects on blood pressure and cardiovascular structure.2. Male GH rats on normal or low‐Na diets were treated with the NOS inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) from the age of 7 to 12 weeks and were given either valsartan (10 mg/kg per day) or felodipine (30 mg/kg per day).3. Systolic blood pressure (SBP; tail‐cuff) was measured weekly. At 12 weeks of age, mesenteric resistance arteries (MRA) were fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained. Stereological analysis was used to obtain MRA media width, lumen diameter, ratio of media width/lumen diameter (M/L) and medial cross‐sectional area (CSA). Left ventricular (LV) mass was determined.4. In GH L‐NAME‐treated rats on a normal diet, SBP was significantly reduced (P < 0.001) by valsartan and felodipine, as was LV mass (valsartan P < 0.001; felodipine P < 0.05). A low‐Na diet with valsartan caused a further fall in SBP (P < 0.01) but, with felodipine, SBP increased in rats on a low‐Na diet (P < 0.05).5. Valsartan with the low‐Na diet had no further effect on LV mass, but the felodipine‐treated group on a low‐Na diet had a lower LV mass (P < 0.05) than rats on a normal diet.6. In MRA from the GH L‐NAME + valsartan‐treated group, there was hypotrophic inward remodelling; the M/L ratio was reduced (P < 0.001) compared with GH L‐NAME‐treated rats. The lumen was outwardly remodelled in the group on the low‐Na diet.7. The GH L‐NAME + felodipine‐treated group showed hypotrophic outward remodelling and a reduction in M/L ratio compared with the GH L‐NAME‐treated group (P < 0.001). A low‐Na diet had no further effect on MRA.8. A low‐Na diet + valsartan had beneficial effects on SBP and MRA, where outward remodelling of the lumen occurred and, thus, resistance was reduced. In contrast, felodipine with a low‐Na diet increased SBP, reduced LV mass and had no effect on MRA structure. Valsartan treatment with a low‐Na diet confers extra benefits on blood pressure and MRA structure.
Effects Of Hydrogen Peroxide On The Transient Outward Current In Rabbit Atrial Myocytes
Authors: Tanaka Hideo , Habuchi Yoshizumi , Suto Fumiaki , Morikawa Junichiro 
Published: March 2003

SUMMARY1. In the present study, we investigated the effects of hydrogen peroxide (H2O2) on the 4‐aminopyridine‐sensitive transient outward current (ITO) in rabbit atrial myocytes using the amphotericin B‐perforated patch voltage‐clamp method.2. Superfusion of myocytes with H2O2 at 100 μmol/L gradually slowed the time‐course of inactivation of ITO and increased the peak by 9% (n = 9). The H2O2‐induced slowing of ITO inactivation was concentration dependent (over the concentration range 10 μmol/L to 1 mmol/L). These effects were hardly reversed by washout of H2O2, but were quickly abolished by dithiothreitol (2 mmol/L).3. Bisindolylmaleimide (100 nmol/L), an inhibitor of protein kinase C, significantly attenuated the H2O2‐induced effects on ITO.4. These results suggest that rabbit atrial ITO is susceptible to oxidation by H2O2 at concentrations relevant to those encountered during ischaemia/reperfusion and that protein kinase C modulates the effects of H2O2.
Nitric Oxide Synthase Activity In Adrenocorticotrophin‐Induced Hypertension In The Rat
Authors: Turner Sw , Mangos Gj , Whitworth Ja 
Published: March 2003

SUMMARY1. The nitric oxide (NO) system has been implicated in the pathogenesis of various forms of experimental hypertension. We studied nitric oxide synthase (NOS) activity as a possible indicator of NO production in adrenocorticotrophin (ACTH)‐induced hypertension in the rat.2. Haemodynamic, metabolic and biochemical parameters were examined in sham (saline)‐ and ACTH (100 μg/kg per day)‐treated male Sprague‐Dawley rats (n = 20).3. Adrenocorticotrophin treatment increased systolic blood pressure, serum corticosterone, adrenal NOS activity and adrenal nitrate and nitrite concentrations and decreased bodyweight and plasma nitrate/nitrite.4. Previous observations of diminished NO production in ACTH‐ and corticosterone‐induced hypertension in the rat were confirmed, but could not be explained by reduced NOS activity in the present study.
Effect Of α‐Adrenoceptor Blockade On The 0.4 Hz Sympathetic Rhythm In Conscious Rats
Authors: Barrès Christian , Neto Edmundo Pereira de Souza , Julien Claude 
Published: March 2003

SUMMARY1. The present study examined the origin of the 0.4 Hz rhythm in renal sympathetic nerve activity (RSNA) in rats. It was anticipated that, after elimination of 0.4 Hz oscillations of arterial pressure (AP) by α‐adrenoceptor blockade, the persistence or disappearance of a 0.4 Hz rhythm in RSNA would point to an endogenous (central oscillator) or baroreflex origin, respectively.2. Arterial pressure and RSNA were recorded in seven conscious rats, before and after acute α‐adrenoceptor blockade with phentolamine (5 mg/kg, i.v.). In each condition, power and coherence spectra were calculated over 15 min periods of rest.3. In control conditions, highly coherent AP and RSNA oscillations were observed near 0.4 Hz. After phentolamine administration, spectral power in the mid‐frequency (0.27–0.74 Hz) band was significantly reduced for both AP and RSNA and maximum power was shifted towards 0.7 Hz.4. The disappearance of the RSNA rhythm at 0.4 Hz after phentolamine administration favours the hypothesis of a baroreflex origin. The new oscillation near 0.7 Hz can derive either from the activity of a previously unrecognized central oscillator or from a faster feedback mechanism involving cotransmitters of noradrenaline acting with shorter time constants (e.g. ATP).
Endothelin Blockade In Angiotensin Ii Hypertension: Prevention And Treatment Studies In The Rat
Authors: Ficai Sylvia , Herizi Abderraouf , Mimran Albert , Jover Bernard 
Published: March 2003

SUMMARY1. The participation of endothelin (ET) in the development and maintenance of hypertension induced by angiotensin (Ang) II was assessed using the non‐specific ET receptor antagonist bosentan (30 mg/kg per day).2. In the prevention study, bosentan was given 24 h prior to and during the 17 day period of AngII infusion (200 ng/kg per min, s.c., osmotic pump), whereas in the treatment study, bosentan was administered from day 10 to day 17. Tail‐cuff pressure (TCP) was measured before and on days 10 and 17 of AngII infusion. At the end of studies, heart weight index was calculated as the ratio of heart to bodyweight (HWI) and the wall thickness of the carotid artery (perfusion/fixation at 120 mmHg) was measured. Tail‐cuff pressure increased from 129 ± 3 to 179 ± 7 and 189 ± 9 mmHg on days 10 and 17 of AngII infusion, respectively.3. Final TCP was markedly lowered in rats pretreated with bosentan, whereas TCP remained comparable with untreated hypertensive rats when bosentan was given from day 10 of AngII infusion (177 ± 9 mmHg).4. The increase in cardiac mass associated with AngII hypertension was similarly attenuated in the two groups receiving bosentan.5. The HWI was 3.49 ± 0.12 mg/g in untreated hypertensive rats and 3.18 ± 0.08 and 3.11 ± 0.09 mg/g in rats pretreated with bosentan and those receiving the antagonist from day 10.6. The increase in carotid wall thickness induced by AngII was prevented, but not reversed, by bosentan.7. These results support the hypothesis that endogenous ET participates only in the initial phase of AngII hypertension. In addition, the beneficial effect of bosentan of cardiac mass but not on arterial wall thickness is in favour of a role of ET as a local mediator of the cardiac hypertrophic effect of AngII, independently of the level of blood pressure and duration of hypertension.
Progress In Reducing The Burden Of Stroke*
Authors: Chalmers John , Chapman Neil 
Published: March 2003

SUMMARY1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non‐fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today.2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations.3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35–40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke.4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin‐converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide.5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.
RENIN GENE EXPRESSION: THE SWITCH AND THE FINGERS
Authors: Morris Brian J , Adams David J , Weyden Louise van der 
Published: March 2003

SUMMARY1. Now that many of the factors and control elements that regulate renin transcription have been identified, the scene is set to address the question of the mode of control.2. Based on current gene control theories, either renin gene transcription in each cell undergoes gradual responses over a continuous range or transcription is switched completely on or completely off. The latter model of ‘binary’ or ‘variegated’ expression fits with observations such as the ‘recruitment’ of new cells for renin expression during strong physiological stimulation and the progressive switching off of expression during development.3. The renin gene offers an excellent general model for testing the mode of control of genes that are subject to continuous modulatory influences from the demands of physiological perturbations. This is because the promoter is well characterized and is subject to the influence of a strong far‐upstream enhancer, one of the key elements of the variegation model.4. Renin is also controlled at the post‐transcriptional level and this, like transcriptional control, involves cAMP mechanisms. We have cloned the human and mouse homologues of a protein (ZNF265) that is important in renin mRNA processing and stability. This uses ‘zinc fingers’ to bind the mRNA. The role of this and other proteins in splicing and stabilization of mRNA is now being elucidated.5. Unravelling the mechanisms that determine rate of supply of renin mRNA to the biosynthetic machinery is being assisted by advances in concepts and techniques in the rapidly moving field of genomics.
Glutamatergic Neural Transmission In The Nucleus Tractus Solitarius:N‐Methyl‐D‐Aspartate Receptors
Authors: Bonham Ann C , Chen Chao‐Yin 
Published: March 2003

SUMMARY1. The nucleus tractus solitarius (NTS) is the first central site where the reflex control of autonomic, including baroreceptor, reflex function is coordinated. Autonomic signals are transmitted from the first‐order visceral afferent fibres to second‐order NTS neurons byL‐glutamate. It is well established that activation of theα‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid (AMPA) receptors, which mediate the fast component ofL‐glutamate signalling, is required for generating changes in membrane potentials of the second‐order NTS neurons. The contribution of the slower‐developing, longer‐lastingN‐methyl‐D‐aspartate (NMDA) receptor‐mediated component of glutamate signalling to synaptic transmission at these synapses is less well understood.2. The aim of this work is to highlight evidence that functional NMDA receptors exist on second‐order NTS neurons in autonomic, including baroreceptor, afferent pathways by determining whether NMDA receptors can be activated by: (i) exogenous application of NMDA; and (ii) endogenous release ofL‐glutamate from autonomic afferent fibres. Studies were performed on second‐order neurons in transverse and horizontal brainstem slices containing the intermediate NTS and the tractus solitarius. Second‐order NTS neurons were identified by electrophysiological criteria or by attached fluorescent‐labelled aortic depressor nerve (ADN) boutons.3. N‐Methyl‐D‐aspartate (50 nmol–2μmol) dose‐dependently evoked excitatory post‐synaptic currents in second‐order NTS neurons (P= 0.004;n= 4). The NMDA receptor‐mediated currents were also synaptically evoked by low‐frequency stimulation of the autonomic afferent fibres in the tractus solitarius. The NMDA receptor‐mediated currents were blocked by the NMDA receptor antagonist AP5 (n= 7;P= 0.027).4. The findings suggest that functional NMDA receptors exist on second‐order NTS neurons. While the NMDA receptor‐ mediated currents may not be required for signal transmission when the second‐order neurons are at resting membrane potential, their activation may help to modulate autonomic signal transmission in the NTS under conditions in which the membrane is depolarized by high frequency or convergent inputs.
Baicalin‐Induced Vascular Response In Rat Mesenteric Artery: Role Of Endothelial Nitric Oxide
Authors: Huang Yu , Tsang Suk Ying , Yao Xiaoqiang , Lau Chi Wai , Su Ya Lun , Chen Zhen Yu 
Published: March 2003

SUMMARY1. Baicalin was isolated and purified from the dry roots of Scutellaria baicalensis Georgi (Huangqin; a traditionally used Chinese medicinal herb) and its effect on the contractility of rat isolated mesenteric arteries was investigated and the role of the endothelium was examined.2. The concentration‐dependent contractile response to U46619 was enhanced by 10–5 mol/L baicalin in endothelium‐intact rings, but this effect was abolished in the presence of 10–4 mol/L NG‐nitro‐L‐arginine or in endothelium‐denuded rings.3. Pretreatment of endothelium‐intact rings with baicalin (3 × 10–5 mol/L) markedly attenuated the relaxant response to A23187, thapsigargin and acetylcholine.4. The present results indicate an important role for endothelial nitric oxide (NO) in the vascular response to baicalin. Baicalin appears to inhibit NO production and release in the endothelium and this mechanism is likely to be responsible for the enhancement of the U46619‐induced contraction and for inhibition of endothelial NO‐mediated relaxation by baicalin in rat mesenteric artery.
Nicorandil Improves Myocardial High‐Energy Phosphates In Postinfarction Porcine Hearts
Authors: Murakami Yo , Wu Xiaoyun , Zhang Jianyi , Ochiai Koichi , Bache Robert J , Shimada Toshio 
Published: March 2003

SUMMARY1. Nicorandil is a potent vasodilator combining the effects of a nitrate with an ATP‐sensitive potassium channel (KATP) opener. Because the postinfarct remodelled heart has increased vulnerability to subendocardial hypoperfusion, it is possible that the vasodilator effects of nicorandil could cause transmural redistribution of blood flow away from the subendocardium. Alternatively, the KATP channel opening effects of nicorandil could exert a beneficial effect on mitochondrial respiration. Consequently, the present study was performed to examine the effect of nicorandil on energy metabolism in the postinfarct heart.2. Studies were performed in swine in which myocardial infarction produced by proximal left circumflex coronary artery ligation had resulted in left ventricular remodeling. [31P] nuclear magnetic resonance spectroscopy (MRS) was used to examine the myocardial energy supply/demand relationship across the left ventricular wall while the transmural distribution of blood flow was examined with radioactive microspheres. Data were obtained during baseline conditions and during infusion of nicorandil (100 μg, i.v., followed an infusion of 25 μg/kg per min).3. Nicorandil caused coronary vasodilation with a preferential increase in subepicardial flow; however, subendocardial flow also increased significantly. Nicorandil had no significant effect on the rate–pressure product or myocardial oxygen consumption. The ratio of phosphocreatine (PCr)/ATP determined with MRS was abnormally depressed in remodelled hearts (2.01 ± 0.11, 1.85 ± 0.10 and 1.59 ± 0.11 for subepicardium, midwall and subendocardium, respectively) compared with normal (2.22 ± 0.11, 2.01 ± 0.15 and 1.80 ± 0.09, respectively). Nicorandil had no effect on the high‐energy phosphate content of normal hearts. However, nicorandil increased the PCr/ATP ratio in the subendocardium of remodelled hearts from 1.59 ± 0.11 to 1.87 ± 0.10 (P < 0.05).4. Although nicorandil caused modest redistribution of blood flow away from the subendocardium of the postinfarct left ventricle, this was associated with an increase of the PCr/ATP ratio towards normal. These results suggest that nicorandil exerts a beneficial effect on energy metabolism in the subendocardium of the postinfarct remodelled left ventricle.
Effect Of Grapefruit Juice On Plasma Chloroquine Kinetics In Mice
Authors: Ali BH , Al‐Qarawi A , Mousa HM 
Published: March 2003

SUMMARY1. It is known that grapefruit juice (GFJ) may interact with drugs concomitantly administered by inhibiting first‐pass metabolism during the intestinal absorption phase. However, its interaction with chloroquine has not been studied previously.2. Grapefruit juice (4 mL/kg) was given orally to mice 1 h prior to oral administration of chloroquine (100 mg/kg) and the concentration of the latter drug was measured fluorometrically in the plasma 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18 and 24 h after its administration.3. The mean (±SEM) of area under the curve values after administration of water ± control) and GFJ were 5.34 ± 0.38 and 7.01 ± 0.66 mg·h/L, respectively. The corresponding mean Cmax values were 763.4 ± 39.1 and 859.2 ± 45.2 mg/L and the corresponding Tmax values (median) were 2.65 and 2.95 h.4. The results suggest that GFJ coingestion increased the plasma concentration of chloroquine and altered some kinetic parameters of chloroquine. The clinical significance of this interaction in patients with malaria needs to be investigated.
Roles of adenosine in skeletal muscle during systemic hypoxia
Authors: Marshall Janice M 
Published: March 2003

Summary1. The present review is concerned with the effects of acute systemic hypoxia on the gross vascular conductance of skeletal muscle (MVC) and on the behaviour of muscle microcirculation.2. On the basis of experiments performed in the rat, it is argued that adenosine released from the vascular endothelium plays a major role in dilating muscle vasculature by acting on adenosine A1 receptors.3. The dilatation of the proximal arterioles is primarily important in increasing MVC and in limiting the fall in O2 delivery to muscle. It is suggested that the action of adenosine on proximal arterioles is dependent on nitric oxide (NO) rather than mediated by NO, such that adenosine dilates the proximal arterioles via other mechanisms when synthesis of NO is blocked.4. In contrast, dilatation of terminal arterioles, particularly in regions within muscle where the hypoxia is most severe, helps to improve the distribution of available O2, allowing muscle O2 consumption to be maintained by increased O2 extraction. It is concluded that the action of adenosine on terminal arterioles is mainly mediated by NO arising from stimulation of endothelial A1 receptors.5. Therefore, adenosine plays a major role in coordinating the behaviour of muscle vasculature such that the relationship between O2 supply and O2 demand can be optimized even when the O2 content of the arterial blood is greatly reduced.
Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat
Authors: González Paquita , Mauriz José Luís , Jiménez Rafael , González‐Gallego Javier , Tuñón María Jesús 
Published: March 2003

Summary1. The effects of the administration piperacillin on bile flow and biliary lipid secretion were studied in male Wistar rats.2. Intravenous injection of piperacillin at doses ranging from 0.3 to 3.0 mmol/kg bodyweight led to an increase in its biliary concentration and excretion rate. Maximal biliary excretion was reached at a dose of 2.0 mmol/kg piperacillin.3. Excretion of the antibiotic into bile was associated with a marked choleresis. A linear relationship was observed between bile flow and piperacillin excretion, 5.7 µL bile being produced per µmol piperacillin excreted into the bile.4. Continuous i.v. infusion of piperacillin at 2.0 mmol/100 g per min did not result in significant changes in bile acid or cholesterol secretion, but biliary phospholipid secretion was markedly reduced. The inhibitory effect on phospholipid secretion was also present when biliary lipid output had been previously increased by an infusion of taurocholate (200 nmol/100 g per min). Addition of taurocholate did not reverse the impairment of phospholipid secretion induced by piperacillin.5. These results indicate that acute administration of piperacillin in the rat induces a marked choleresis by stimulating bile acid‐independent bile flow. The significant impairment in phospholipid secretion suggests a specific effect on intracellular supply and/or translocation across the canalicular membrane.
Intravascular granulocyte aggregates caused by the selectin‐binding carbohydrate fucoidin in pig kidneys
Authors: Dittrich Sven , Lippek Frank , Gratopp Alexander , Grosse‐Siestrup Christian , Lange Peter E , Bührer Christoph 
Published: March 2003

Summary1. Renal postischaemic reperfusion injury constitutes a significant problem after kidney transplantation. The polysaccharide fucoidin improves postischaemic function in lamb hearts, presumably by blocking selectin‐mediated leucocyte adhesion.2. In the present study, eight pairs of ischaemic pig kidneys were reperfused in an ex vivo model with autologous blood with or without fucoidin (100 mg/L).3. Fucoidin resulted in a significant decrease in renal blood flow (45 ± 5 vs 178 ± 22 mL/min per 100 g; P < 0.001) and increased vascular resistance (3.80 ± 0.07 vs 0.60 ± 0.12 mmHg/mL per min per 100 g; P < 0.001).4. Histological examination revealed granulocyte emboli in afferent glomerular arteries in five of six fucoidin‐treated kidneys and in one of six controls (Fisher's exact test; P < 0.001).5. In vitro experiments with human granulocytes showed that large granulocyte aggregates were induced by fucoidin at concentrations similar to those used in reperfused kidneys, whereas slightly lower doses of fucoidin prevented l‐selectin‐dependent homotypic granulocyte adhesion.6. The formation of embolizing granulocyte aggregates defines a narrow therapeutic range for fucoidin and calls into question its experimental use as an inhibitor of selectin‐mediated leucocyte adhesion.