bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective Effect Of Resveratrol On Oxidative Damage In Male And Female Stroke‐Prone Spontaneously Hypertensive Rats
Authors: Mizutani Kenichi , Ikeda Katsumi , Kawai Yasuhiro , Yamori Yukio 
Published: March 2003

SUMMARY1. In the present study, we examined the effect of resveratrol (3,4′,5‐trihydroxystilbene), a phytoestrogen found in the skins of most grapes, on oxidative DNA damage in male and female stroke‐prone spontaneously hypertensive rats (SHRSP).2. Five‐week‐old male and female SHRSP were divided into control and resveratrol groups. The resveratrol group was given 1 mg/kg per day, orally, resveratrol by gastric intubation once a day.3. Following an 8 week feeding period, the levels of 8‐hydroxydeoxyguanosine (8‐OHdG), produced from deoxyguanosine under conditions of oxidative stress, in the urine of male and female resveratrol‐treated SHRSP were significantly lower than that in control SHRSP.4. The urine of resveratrol‐treated male and female SHRSP had lower levels of hydroperoxide compared with control SHRSP, but the difference was not significant.5. Treatment with resveratrol resulted in a 25 and 30% reduction in plasma glycated albumin in male and female SHRSP, respectively, compared with controls.6. Gender differences for SHRSP with regard to 8‐OHdG, hydroperoxide and glycated albumin levels were not confirmed, resveratrol having similar protective effects on male and female SHRSP.7. These results indicate that dietary resveratrol: (i) plays a role in suppressing oxidative DNA damage and glycoxidative stress in vivo; and (ii) has similar protective effects in both male and female SHRSP, suggesting that the direct effects of this phytoestrogen on oxidative stress in vivo are not sexually dimorphic.
Comparison Of Digoxin Versus Low‐Dose Amiodarone For Ventricular Rate Control In Patients With Chronic Atrial Fibrillation
Authors: Tse Hung‐Fat , Lam Yui‐Ming , Lau Chu‐Pak , Cheung Bernard My , Kumana Cyrus R 
Published: March 2003

SUMMARY1. Rapid ventricular rate (VR) and rhythm irregularity during atrial fibrillation (AF) impair cardiac performance. Although digoxin has been widely used in patients with AF, its efficacy for the control of VR and rhythm irregularity is unsatisfactory. Whether low‐dose amiodarone is more effective remains unclear.2. We randomized 16 patients (13 male, three female; mean (±SD) age 63 ± 9 years) with chronic AF to receive either digoxin or amiodarone for 24 weeks. At baseline and at 12 and 24 weeks follow up, Holter monitor recording and cardiopulmonary exercise test were performed to assess VR and rhythm irregularity control and exercise capacity.3. Seven and nine patients received digoxin and amiodarone, respectively. After 12 and 24 weeks treatment, both digoxin and amiodarone significantly decreased the mean ambulatory VR and the VR during peak exercise compared with baseline (all P < 0.05). At 24 weeks, there were no significant differences between digoxin and amiodarone in the percentage reduction in VR during ambulatory (27 ± 13 vs 25 ± 12%, respectively; P = 0.8) and peak exercise (13 ± 12 vs 12 ± 10%%, respectively; P = 0.6).4. The rhythm irregularity, as measured by SD of RR intervals and the root mean square of the SD of RR intervals, and the exercise capacity, as measured by exercise workload, maximal oxygen consumption (VO2), minute ventilation, ventilatory equivalent and oxygen pulse, were not significantly changed after treatment with digoxin or amiodarone (all P > 0.05).5. Quality of life, determined by SF‐36 questionnaire, and AF symptomatology, as measured by the AF Symptom Checklist, were also not significantly changed after treatment with digoxin or amiodarone (all P > 0.05).6. In conclusion, digoxin and low‐dose amiodarone had similar efficacy in the control of VR during ambulatory activity and exercise. However, both were less efficacious during exercise and did not significantly affect rhythm irregularity, exercise capacity, quality of life and AF symptomatology in patients with chronic AF.
Effects Of Digoxin, Furosemide, Enalaprilat And Metoprolol On Endothelial Function In Young Normotensive Subjects
Authors: Mühlen B von zur , Millgård J , Lind L 
Published: March 2003

SUMMARY1. Endothelial dysfunction is seen in patients with essential hypertension or congestive heart failure (CHF). The present study aimed to evaluate the direct effect on endothelium‐ dependent vasodilation (EDV) of different pharmacological drugs commonly used in the treatment of these conditions.2. Forearm blood flow (FBF) was measured in 37 young healthy normotensive subjects with venous occlusion plethysmography during local intra‐arterial infusions of methacholine (MCh; 2–4 μg/min), evaluating EDV, and sodium nitroprusside (SNP; 5–10 μg/min), evaluating endothelium‐independent vasodilation (EIDV). The measurements of EDV and EIDV were undertaken under baseline conditions and were repeated after 1 h intra‐arterial infusion of digoxin (0.1 mg/h), furosemide (5.0 mg/h), enalaprilat (2,4 mg/h), metoprolol (1.2 mg/h) or saline (controls).3. Enalaprilat and digoxin improved the FBF response to MCh at 4 μg/min (from 22.7±2.3 to 25.5±2.1 mL/min per 100 mL tissue (P < 0.01) and from 18.2±2.4 to 22.2±2.0 mL/min per 100 mL tissue (P < 0.05), respectively). No significant changes where induced by furosemide or metoprolol in response to MCh at 4 μg/min (from 19.4±2.0 to 22.9±2.8 and from 15.3±2.4 to 14.7±1.1 mL/min per 100 mL tissue, respectively). No significant changes in basal FBF or EIDV were induced by the different drugs. When the endothelial function index was calculated as the MCh : SNP FBF ratio, a significant improvement was seen only with enalaprilat (1.1±0.1 to 1.2±0.1; P < 0.01) and furosemide (1.0±0.1 to 1.3±0.4; P < 0.05).4. In conlusion, the results of the present study show that enalaprilat and furosemide improve endothelial vasodilatory function, while no major effect was induced by digoxin or metoprolol. Thus, different direct effects on the endothelium in young normotensive subjects were induced by drugs commonly used in the treatment of hypertension or CHF.
Ouabain‐Induced Coronary Vasoconstriction In Cats Is Not Neurally Mediated
Authors: Nair Balagopalan A , Murad Yasemin Z , Brody Michael J , Gutterman David D 
Published: March 2003

SUMMARY1. Previous reports indirectly implicate a neural mechanism for coronary constriction to centrally administered digitalis. However, autoregulatory changes in coronary resistance due to changes in arterial pressure may have influenced the interpretation of these studies.2. We tested directly the hypothesis that cardiac sympathetic innervation is responsible for coronary constriction to ouabain by examining the effects of ouabain (intravenous (i.v.) and intracerebroventricular (i.c.v.)) before and after bilateral stellate ganglionectomy.3. Cats were anaesthetized and instrumented for the measurement of heart rate, blood pressure and coronary blood flow velocity using an epicardial‐attached suction Doppler probe. Animals were treated with atenolol and the effects of either i.v. or i.c.v. injections of ouabain were examined.4. In seven cats treated with atenolol, i.v. ouabain (0.11 mg/kg) produced maximal increases in arterial pressure and coronary vascular resistance index (CVRI) of 66 ± 7 mmHg and 37 ± 9%, respectively. Following bilateral stellate ganglionectomy (n = 7), ouabain produced similar increases in arterial pressure (70 ± 9 mmHg) and CVRI (39 ± 7%). A higher dose of i.v. ouabain (1.1 mg/kg) produced maximal increases in arterial pressure (115 ± 4 mmHg) and coronary resistance (86 ± 14%) in intact cats (n = 6) that were similar to responses seen in cats in which stellate ganglionectomy had been performed (n = 6; arterial pressure 104 ± 13 mmHg; coronary resistance 114 ± 6%). The increases in coronary resistance to ouabain at both doses were significantly greater than increases in coronary resistance to passive elevation of arterial pressure during aortic constriction. Thus, autoregulation does not explain fully the coronary constriction to ouabain.5. To further examine a central mechanism, i.c.v. perfusion with 0.3 mmol/L ouabain was performed in six cats, resulting in increases in arterial pressure (122 ± 7 mmHg) and coronary resistance (58 ± 14%). Similar increases in arterial pressure (117 ± 16%) and coronary resistance (84 ± 20%) were seen in separate studies (n = 6) following stellate ganglionectomy.6. These results indicate that coronary constriction to ouabain does not require intact cardiac sympathetic innervation, but probably involves a direct or humorally mediated effect.
Mechanisms Of Endothelin‐1‐Induced Potentiation Of Noradrenaline Response In Rat Mesenteric Artery
Authors: Matsumura Yasuo , Kita Satomi , Okui Tomoko 
Published: March 2003

SUMMARY1. Subthreshold concentrations of endothelin (ET)‐1 enhance the contractile responses to noradrenaline (NA). We investigated possible mechanisms underlying the ET‐1‐induced enhancement of vasoconstrictor responses to NA in rat perfused mesenteric arteries.2. Perfusion of arteries with subpressor dose of ET‐1 (3 × 10–10 mol/L) significantly potentiated the pressor responses to NA (10–6, 3 × 10–6 and 10–5 mol/L) and this action of ET‐1 was endothelium independent.3. The protein kinase C (PKC) inhibitors staurosporine (10–8 mol/L) and calphostin C (10–7 mol/L) markedly attenuated the ET‐1‐induced enhancement of NA responses. Vasoconstrictor responses to NA were potentiated when vessels were perfused with phorbol 12‐myristate 13‐acetate (10–8 mol/L).4. The potentiating effect of ET‐1 was efficiently suppressed by Y‐27632 (10–6 mol/L), a selective Rho‐kinase inhibitor. In the presence of both staurosporine and Y‐27632, contractile responses to NA alone were decreased markedly and ET‐1‐induced potentiation was abolished.5. Both staurosporine and Y‐27632 decreased contractile responses to NA in arteries of deoxycorticosterone acetate (DOCA)‐salt hypertensive rats to levels observed in normotensive control animals.6. These findings suggest that ET‐1‐mediated potentiation of responses to NA occurs through activation of either PKC or Rho‐kinase. This mechanism seems to contribute to the enhanced vasoconstrictor responces to NA observed in DOCA‐salt hypertensive rats, in which the responses to NA are enhanced tonically by endogenous vascular ET‐1.
Circumventricular Organs: Gateways to the BrainLeptin Receptors In Hypothalamus And Circumventricular Organs
Authors: Meister Björn , Håkansson Marie‐Louise 
Published: March 2003

SUMMARY1. The adipose tissue‐derived hormone leptin reduces food intake and bodyweight via leptin receptors (Ob‐R) in the hypothalamus.2. Leptin receptor immunoreactivity, demonstrated with an antiserum recognizing all Ob‐R isoforms, is present in hypothalamic neurons of the medial and lateral preoptic area, organum vasculosum lamina terminalis, subfornical organ, periventricular, suprachiasmatic, supraoptic (SON), paraventricular (PVN), arcuate (ARC), dorsomedial, ventromedial hypothalamic and tuberomammillary nuclei and lateral hypothalamic area. In the brainstem, Ob‐R immunoreactivity is present in the area postrema, nucleus tractus solitarius, hypoglossal nucleus and dorsal motor nucleus of the vagus nerve.3. Leptin receptor immunoreactivity is present in magnocellular vasopressin and oxytocin neurons of the SON and PVN, in parvocellular corticotropin‐releasing hormone neurons of the PVN, neuropeptide Y and pro‐opiomelanocortin neurons of the ARC and in melanin‐concentrating hormone neurons of the lateral hypothalamic area.4. The passage of leptin across the blood–brain barrier and the chemical mediators of the action of leptin in the hypothalamus are discussed.
Lack Of Association Between Qt Dispersion And Blood Pressure Response During Dental Surgery
Authors: Matsumura Kiyoshi , Miura Keiko , Kurokawa Hideo , Abe Isao , Takata Yutaka 
Published: March 2003

SUMMARY1. It is well known that dental surgery induces increases in blood pressure. However, the factors influencing this increase are not yet fully understood. We have determined the relationship between QTc (= QT/RR1/2, with RR being the R‐R interval in seconds) dispersion, measured with a 12‐lead surface electrocardiogram, and changes in blood pressure during tooth extraction.2. Both QTc dispersion and the power spectrum of R‐R variability were determined before the dental surgery was undertaken. The low‐frequency (LF; 0.041–0.140 Hz), high‐ frequency (HF; 0.140–0.500 Hz) and total spectral powers (TF; 0.000–4.000 Hz) were calculated and the ratio of LF to HF and the percentage of HF relative to TF (%HF; HF/TF × 100) were used as indices of sympathovagal balance and parasympathetic activities, respectively.3. In the present study, QTc dispersion failed to correlate with LF/HF and %HF. Systolic blood pressure and pulse rate increased significantly during tooth extraction; however, changes in these variables failed to correlate with QTc dispersion.4. These results suggest that QTc dispersion is not associated with the power spectrum of R‐R variability and that it does not affect the blood pressure response during tooth extraction.
Vitamin C Prevents Radiation‐Induced Endothelium‐Dependent Vasomotor Dysfunction And De‐Endothelialization By Inhibiting Oxidative Damage In The Rat
Authors: On Young‐Keun , Kim Hyo‐Soo , Kim Seok‐Yeon , Chae In‐Ho , Oh Byung‐Hee , Lee Myoung‐Mook , Park Young‐Bae , Choi Yun‐Shik , Chung Myung‐Hee 
Published: March 2003

SUMMARY1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation‐induced damage of the endothelium.2. Female Sprague‐Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + NG‐nitro‐L‐arginine methyl ester (L‐NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8‐hydroxydeoxyguanosine (OH‐dG) and immunohistochemical staining were measured.3. Irradiation significantly impaired the acetylcholine‐induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L‐NAME (100 μg/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH‐dG in the aorta (1.02 ± 0.27 vs 2.61 ± 0.78 OH‐dG/105 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 ± 0.23 OH‐dG/105 dG; P < 0.01). Irradiation caused significant de‐endothelialization (von Willebrand factor (vWF) staining was 93 ± 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 ± 3%; P < 0.05).4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial‐dependent vasodilation that could be prevented by vitamin C, partly through anti‐oxidant mechanisms.
Effect Of Enalapril On Diabetic Nephropathy In Oletf Rats: The Role Of An Anti‐Oxidative Action In Its Protective Properties
Authors: Sugimoto Koh‐ichi , Tsuruoka Shuichi , Fujimura Akio 
Published: March 2003

SUMMARY1. We have evaluated the effects of the angiotensin‐converting enzyme inhibitor enalapril on renal function and oxidative status in the kidney of Otsuka Long‐Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous onset of type 2 diabetes mellitus.2. Enalapril (5 mg/kg) or vehicle (distilled water) was given once daily by gavage to 22‐week‐old male OLETF rats for 32 weeks. Long‐Evans Tokushima Otsuka (LETO) rats, the control animals for OLETF rats, received vehicle alone (n = 10 in each group).3. Enalapril attenuated the rise in blood pressure mildly, but significantly. Enalapril significantly blunted the development of proteinuria without a significant effect on creatinine clearance. At the end of the study period, the lipid peroxide content in the renal cortex was significantly increased in OLETF compared with LETO rats, in which enalapril had no effect on lipid peroxide content. Enalapril enhanced the activity of catalase in the renal cortex of OLETF rats, but had no effect on the activity of either superoxide dismutase or glutathione peroxidase.4. These results suggest that oxidative stress may be involved in the development of nephropathy in type 2 diabetes. Enalapril exhibited renoprotective effects without changing lipid peroxides in the kidney, suggesting that the beneficial effects of the compound on diabetic renal damage in OLETF rats may not be mediated through an anti‐oxidative action.
Prenatal Exposure To Magnetic Field Increases Dopamine Levels In The Striatum Of Offspring
Authors: Lee Byung‐Cheon , Bing Guoying , Jhoo Wang‐Kee , Yoon Joo‐Mae , Kang Kee‐Seok , Shin Eun‐Joo , Kim Won‐Ki , Ko Kwang Ho , Kim Hyoung‐Chun 
Published: March 2003

SUMMARY1. The putative effects of prenatal exposure to magnetic field (MF) have recently received much interest. In the present study, mice were exposed to a MF of 50 mT during gestation (0–19 days).2. After the exposure was terminated, mothers and offspring were returned to normal laboratory conditions. We then determined changes in striatal levels of dopamine (DA) and its metabolite 3,4‐dihydroxyphenylacetic acid (DOPAC) in the offspring.3. Our results indicate that prenatal exposure to MF increases levels of DA and DOPAC in the striatum at 4, 8 and 12 weeks postnatally.
Design Of Clinical Pharmacology Trials
Authors: Duffull Stephen B 
Published: March 2003

SUMMARY1. There are a variety of methods that could be used to increase the efficiency of the design of experiments. However, it is only recently that such methods have been considered in the design of clinical pharmacology trials.2. Two such methods, termed data‐dependent (e.g. simulation) and data‐independent (e.g. analytical evaluation of the information in a particular design), are becoming increasingly used as efficient methods for designing clinical trials. These two design methods have tended to be viewed as competitive, although a complementary role in design is proposed here.3. The impetus for the use of these two methods has been the need for a more fully integrated approach to the drug development process that specifically allows for sequential development (i.e. where the results of early phase studies influence later‐phase studies).4. The present article briefly presents the background and theory that underpins both the data‐dependent and ‐independent methods with the use of illustrative examples from the literature. In addition, the potential advantages and disadvantages of each method are discussed.
Renal And Cardiac Sympathetic Baroreflexes In Hypertensive Rabbits
Authors: Head Geoffrey A , Burke Sandra L 
Published: March 2003

SUMMARY1. The purpose of the present study was to assess the changes to renal sympathetic nerve activity (RSNA) baroreflexes during the development of hypertension after renal clipping in conscious rabbits.2. Rabbits were fitted with a clip on the right renal artery or underwent a sham operation under halothane anaesthesia. A recording electrode was implanted on the left renal nerve 1 week before the experiment, 3 or 6 weeks after the initial operation. During the experiment, drug‐induced ramp rises and falls in mean arterial pressure (MAP) were used to produce RSNA and heart rate (HR) baroreflex curves. The RSNA for each experiment was calibrated against maximum RSNA evoked by stimulation of baroreceptor‐independent trigeminal afferents.3. Mean arterial pressure was 20 and 36% higher 3 and 6 weeks after clip implantation, respectively. Renal sympathetic nerve activity baroreflex curves were reset rightwards accordingly, but the shape of the RSNA curves was differentially affected.4. At both hypertensive periods, MAP–HR baroreflex gain was markedly reduced due to a reduction in curvature. The HR baroreflex range was increased. The RSNA baroreflex gain was reduced at 3 weeks, which was due to a 35% lower RSNA baroreflex range, but was similar to sham animals at 6 weeks.5. The results show that, in established two kidney, one clip hypertension in rabbits, the sympathetic baroreflex is relatively well preserved but sensitivity of cardiac baroreflexes is attenuated. Therefore, the short‐term inhibition of RSNA baroreflexes is not related to the level of blood pressure or the development of secondary changes, such as cardiac or vascular hypertrophy, but may be related to circulating angiotensin, which is known to increase at this time.
Inhibitory Effects Of Angiotensin Ii On Barosensitive Rostral Ventrolateral Medulla Neurons Of The Rat
Authors: Bertram Delphine , Coote John H 
Published: March 2003

SUMMARY1. The brain renin–angiotensin system can influence arterial baroreceptor reflex control of blood pressure (BP) through both direct and indirect effects on sympathetic premotor neurons of the rostral ventrolateral medulla (RVLM). The present study examined the direct effect of angiotensin (Ang) II applied by microiontophoresis on the ongoing activity of single RVLM neurons.2. In 26 urethane‐anaesthetized Wistar rats, recordings of single unit activities of barosensitive RVLM neurons were made from one barrel of a six‐barrel micropipette assembly. The other five barrels were filled with eitherL‐glutamate, AngII, valsartan (an AT1receptor antagonist), PD 123177 (an AT2receptor antagonist) and saline. All drugs were applied by microiontophoresis.3. Mean BP was 83±3 mmHg. Application of AngII inhibited the ongoing activity of RVLM neurons, identified as barosensitive because their activity was inhibited by a phenylephrine‐ induced increase in BP, from 12.6±1.5 to 5.4±1.1 Hz (n= 24;P< 0.001). Angiotensin II also inhibited the glutamate‐evoked excitation of barosensitive RVLM neurons from 15±3 to 5.8±2.0 Hz (n= 6;P< 0.001). Valsartan significantly increased neuronal activity from 9.5±2.3 to 13.5±3.2 Hz (n= 7,P< 0.01), whereas PD 123177 significantly decreased neuronal activity from 13.5±3.5 to 9.9±2.8 Hz (n= 13;P< 0.01).4. The results suggest that AngII exerts a tonic inhibitory effect on barosensitive RVLM neurons, which is presumably mediated through AT1receptor stimulation.
Glucocorticoid‐Induced Hypertension: From Mouse To Man
Authors: Whitworth Judith A , Schyvens Christopher G , Zhang Yi , Mangos George J , Kelly John J 
Published: March 2003

SUMMARY1. Adrenocorticotrophic hormone (ACTH) raises blood pressure in humans, sheep, rat and mouse. In rat and humans, but not sheep, the hypertension can be explained by glucocorticoid excess.2. In both rat and humans, the hypertension is associated with a rise in cardiac output and renal vascular resistance.3. In both rat and humans, the nitric oxide system is implicated in glucocorticoid hypertension.4. In both rat and humans, hypertension due to naturally occurring glucocorticoids is not prevented by drugs that block classical glucocorticoid or mineralocorticoid receptors.5. Abnormalities in glucocorticoid metabolism may contribute to some forms of ‘essential’ hypertension.