bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHOLINERGIC PREJUNCTIONAL INHIBITION OF NITRERGIC NEUROTRANSMISSION IN THE GUINEA‐PIG ISOLATED BASILAR ARTERY
Authors: Jiang Fan , Li Chun Guang , Rand Michael J 
Published: March 2003

1. The effects of endogenous and exogenous acetylcholine (ACh) on nitrergic relaxations elicited by electrical field stimulation (EFS) were studied in guinea‐pig endothelium‐denuded basilar artery preparations precontracted with 1 μmol/L prostaglandin F2α and a possible role of K+ channels in mediating the effects was investigated.2. Acetylcholine (3 mmol/L) and physostigmine (10 μmol/L) produced small, yet statistically significant, inhibitions of EFS‐induced nitrergic relaxations, while atropine (1 μmol/L) slightly enhanced the nitrergic response. The ACh‐induced inhibition was atropine sensitive. Acetylcholine or atropine did not affect relaxations induced by sodium nitroprusside.3. The inhibition of nitrergic relaxations by 3 μmol/L ACh was prevented by the K+ channel blockers tetraethylammonium and 4‐aminopyridine, but was not changed by iberiotoxin, apamin or glibenclamide.4. Neither vasoactive intestinal polypeptide nor the α2‐adrenoceptor agonists noradrenaline and clonidine modulated nitrergic neurotransmission in the guinea‐pig basilar artery.5. The findings show that ACh acts on prejunctional muscarinic receptors of nitrergic nerves to inhibit nitrergic neurotransmission. It is suggested that endogenous ACh may have this effect; however, the physiological significance of this prejunctional modulation is not clear due to the relatively small effect produced. The prejunctional inhibitory action of ACh may involve opening of neuronal K+ channels.
UROKINASE PLASMINOGEN ACTIVATOR SYSTEM IN HUMANS WITH STABLE CORONARY ARTERY DISEASE
Authors: Krasnikova Tl , Parfyonova YeV , Alekseeva Ia , Arefieva Ti , Mukhina Sa , Dobrovolsky Ab , Titaeva YeV , Lyakishev Aa , Resink Tj , Erne P , Tkachuk Va 
Published: March 2003

1. The present study compares plasma urokinase plasminogen activator (uPA) peptide levels, plasma plasminogen inhibitor (PAI‐1) activity and urokinase receptors (uPAR) on peripheral blood monocytes of patients with stable coronary artery disease (SCAD) and healthy volunteers.2. Urokinase plasminogen activator levels were analysed by ELISA and PAI‐1 activity was determined by a plasmin generation method using the chromogenic substrate S2390. Relative uPAR numbers and the adhesion molecules CD11b/CD18 on peripheral blood monocytes were estimated using specific antibodies and flow cytometry.3. Patients with SCAD were found to have higher plasma uPA peptide levels than age‐matched healthy subjects (10.40±0.99 vs 8.25±0.53 pmol/L, respectively; P < 0.05).4. Plasma PAI‐1 activity was also higher in patients with SCAD than in healthy subjects (13.6±2.5 vs 5.2±1.0 IU/mL, respectively; P < 0.05).5. Relative uPAR and CD11b/CD18 adhesion molecules were similar on peripheral blood monocytes of patients with SCAD and in healthy subjects.6. The data indicate a pattern of expression/activity of uPA and PAI‐1 in patients with SCAD suggestive of an impaired fibrinolytic ability.
PERTUSSIS TOXIN‐SENSITIVE G‐PROTEINS AND REGULATION OF BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Jr Curtis K Kost , Herzer William A , Li Ping J , Jackson Edwin K 
Published: March 2003

1. Increased Gi‐protein‐mediated receptor–effector coupling in the vasculature of the spontaneously hypertensive rat (SHR) has been proposed as a contributing factor in the maintenance of elevated blood pressure. If increased Gi‐protein‐mediated activity plays an important role in hypertension in SHR, then inhibition of Gi‐proteins by pertussis toxin would be expected to decrease blood pressure in this genetic hypertensive model. To address this hypothesis, studies were undertaken comparing the cardiovascular effects of pertussis toxin in SHR and normotensive Wistar‐Kyoto (WKY) rats.2. Spontaneously hypertensive and WKY rats were instrumented with radiotelemetry devices and blood pressure measurements were recorded in conscious rats. Following a single injection of pertussis toxin (10 μg/kg, i.v.), mean arterial blood pressure fell from 161±3 to 146±1 mmHg in the SHR and the effect was sustained for more than 2 weeks. In contrast, 10 μg/kg, i.v., pertussis toxin produced no significant effect on blood pressure in WKY rats (103±4 vs 101±5 mmHg).3. In a separate study, SHR and WKY rats were administered 30 μg/kg, i.v., pertussis toxin or 150 μL/kg, i.v., saline and, 3–5 days later, rats were anaesthetized and instrumented to permit measurement of blood pressure and renal function. At this higher dose, pertussis toxin reduced blood pressure in both strains of rat, although the effect was markedly greater in SHR (approximately 40 mmHg decrease) compared with WKY rats (approximately 15 mmHg decrease). In SHR, pertussis toxin increased renal blood flow (from 5.7±0.3 to 7.5±0.8 mL/min per g kidney) and decreased renal vascular resistance (from 31±2 to 19±2 mmHg/mL per min per g kidney). In WKY rats, pertussis toxin had no significant effect on renal parameters.4. Results from these studies indicate that a pertussis toxin‐sensitive Gi‐protein‐mediated pathway contributes to the maintenance of hypertension and elevated renal vascular tone in the SHR.
DIURNAL VARIATIONS IN INSULIN SECRETION AND K+ PERMEABILITY IN ISOLATED RAT ISLETS
Authors: Delattre E , Cipolla‐Neto J , Boschero Ac 
Published: March 2003

1. The effects of glucose on insulin secretion and 86Rb efflux from isolated rat islets were studied at six different times during a 24‐h period (00.00, 04.00, 08.00, 12.00, 16.00 and 20.00 h).2. In the absence of glucose and in the presence of substimulatory concentrations (2.8 mmol/L) of the sugar, insulin secretion did not vary with the time of day. At a glucose concentration of 5.6 mmol/L the stimulated insulin secretion was greater than basal levels only at 20.00 h.3. At a higher sugar concentration (8.3 mmol/L) the increase in insulin secretion and the reduction in 86Rb efflux rate were more marked during the dark period. No effect of the time of day on insulin secretion was observed at glucose concentrations above 8.3 mmol/L (except in 27.7 mmol/L).4. The time of day appears to affect insulin secretion mainly at glucose concentrations close to physiological values (5.6–8.3 mmol/L).5. This result agrees with the ability of physiological amounts of glucose to alter the 86Rb‐permeability of pancreatic B cells at the same time intervals.
PREVENTIVE NUTRITIONAL FACTORS IN EPIDEMIOLOGY: INTERACTION BETWEEN SODIUM AND CALCIUM
Authors: Mizushima Shunsaku , Tsuchida Kenichi , Yamori Yukio 
Published: March 2003

1. It is generally believed, though difficult to prove, that diet plays a role in the risk of various diseases. Components of difficulties include several issues such as dietary assessment method, regression dilution bias, multicolinearity and interaction among nutrients.2. The present study focuses on colinearity and interaction between sodium and calcium, which should be cautiously examined in nutritional epidemiological studies in relation to blood pressure and bone mineral density.3. The World Health Organization’s International Cooperative Cardiovascular Diseases and Alimentary Comparison study showed significant multicolinearity among urinary sodium, calcium and urea nitrogen as well as urinary calcium and magnesium. Urinary sodium and calcium had significant correlation (r = 0.438, P < 0.05, n = 48) by cross‐centre analysis.4. Interaction between sodium and calcium on bone mineral density is studied using the data set from bone mineral density screening for 1658 females, aged 20–40 years, in Yokohama, Japan. Among those who have lower calcium intake (< 600 mg/day), higher calcium intake (%) from small fish, which is likely to be associated with a high salt diet, related to significantly lower mineral bone density.5. Interaction between sodium and calcium on bone mineral density among young Japanese females is suggested. Moderate sodium restriction is needed for prevention of not only cardiovascular diseases but also osteoporosis.
GENETIC ANALYSIS IN DAHL SALT‐SENSITIVE RATS
Authors: Kato Norihiro 
Published: March 2003

1. To investigate predisposition to hypertension in Dahl salt‐sensitive rats, genome‐wide screens were performed in F2 populations.2. Several quantitative trait loci (QTL) for blood pressure were detected, of which some were shown to confer susceptibility genes by the construction of congenic animals carrying relevant chromosome fragments.3. Chromosome regions homologous to one QTL (on rat chromosome 10) were recently shown to be linked to hypertension in humans. Thus, there is a possibility that a ‘common’ susceptibility gene causes hypertension in both species.
LOW DOSE INDAPAMIDE PLUS PERINDOPRIL COMBINATION EFFECTS ON CARDIOVASCULAR STRUCTURE AND FUNCTION IN GENETIC HYPERTENSION
Authors: Ibrahim Jamila , Schachter Michael , Hughes Alun D , Sever Peter S 
Published: March 2003

1. Although the fixed combination preparations of thiazide and angiotensin‐converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long‐term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P, S5590) in spontaneously hypertensive rats (SHR) were examined in the present study.2. Male SHR (10–12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire‐myography.3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross‐sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium‐ independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment.4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.
CHANGES OF URINARY DOPAMINE EXCRETION EARLY AFTER BALLOON MITRAL COMMISSUROTOMY IN MITRAL STENOSIS
Authors: Hayashi Manabu , Takizawa Hideki , Tsuchihashi Kazufumi , Ura Nobuyuki , Shimamoto Kazuaki 
Published: March 2003

1. In order to investigate the changes of reduced urinary free dopamine excretion (uDA) in heart failure, 15 patients with symptomatic mitral stenosis were investigated on their uDA, endogenous creatinine (Cr) clearance, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline (pNA) and plasma L‐dopa concentration before and early after percutaneous transvenous mitral commissurotomy (PTMC) by the clearance study. The delivery of L‐dopa to renal proximal tubules (plasma L‐dopa × Cr clearance), and the conversion ratio of plasma L‐dopa to urinary dopamine in the kidney [uDA/(plasma L‐dopa × Cr clearance)] were also estimated.2. After successful PTMC, uDA, UNaV and FENa showed a significant but incomplete improvement and the changes of uDA were correlated positively with those of cardiac index (CI) (r = 0.665, P < 0.01), not with changes of pulmonary wedge pressure. While plasma L‐dopa and plasma L‐dopa × Cr clearance improved, uDA/(plasma L‐dopa × Cr clearance) was not significantly changed early after PTMC.3. From these results, it was suggested that reduced uDA tended to increase incompletely in relation with functional recovery of heart, and that increased plasma L‐dopa and a delivery of L‐dopa to renal proximal tubules have some positive role on urinary dopamine excretion, at least, early after PTMC.
Participation Of Central and Peripheral κ1 and κ2 Opioid Receptors In Arrhythmogenesis
Authors: Lishmanov Yury B , Maslov Leonid N , Ugdyzhekova Dina S 
Published: March 2003

SUMMARY1. The κ1 and κ2 opioid receptor agonists U‐62066 (8 mg/kg, i.p.) and (–)‐bremazocine (0.7 mg/kg, i.v.), respectively, both exhibit anti‐arrhythmic properties against adrenaline‐induced dysrhythmias in rats.2. In contrast, (+)‐bremazocine has no effect on adrenaline‐induced dysrhythmias.3. The κ1 opioid receptor agonists U‐50 488 (110 nmol) and [
D‐Ala
2]‐dynorphin A (20 nmol) and the κ2 opioid receptor agonist (–)‐bremazocine (30 nmol) exhibit pro‐arrhythmic properties following intracerebroventricular administration.4. Prior administration of the κ opioid receptor antagonist nor‐binaltorphimine doses i.c.v. (14 nmol), i.p. (10 mg/kg), completely abolishes the pro‐arrhythmic (BNI, i.c.v., 14 nmol) as well as anti‐arrhythmic (BNI, 10 mg/kg, i.p.) effects of the κ opioid receptor agonists.5. Neither hexamethonium (10 mg/kg, i.v.) nor atropine (1 mg/kg, i.v.) have any effect on the anti‐arrhythmic actions of the κ1 opioid receptor agonist U‐62066 following systemic administration.6. It is suggested that the anti‐arrhythmic effects of U‐62066 and (–)‐bremazocine are associated with the activation of peripheral κ opioid receptors and do not depend on the activation of κ opioid receptors in the autonomic nervous system.
FOETAL FLUID BALANCE AND HORMONE STATUS FOLLOWING NEPHRECTOMY IN THE FOETAL SHEEP
Authors: Moritz Karen M , Macris Mary , Talbo Gert , Wintour E Marelyn 
Published: March 2003

SUMMARY1. The role of the kidneys in the maintenance of normal foetal plasma (FP) composition and hormone concentrations was examined in the present study. Five ovine foetuses were chronically cannulated and nephrectomized (nephx) at 100±1 days of gestation and maintained for 14 days. These were compared to five intact control foetuses.2. Four hours after nephx, FP renin concentrations were significantly lower than in control foetuses. By 48 h, renin concentrations in nephx foetuses were below the level of detectability of the assay. Foetal plasma aldosterone concentrations declined in nephx foetuses, but were not significantly different to those in control foetuses (P = 0.08).3. During the second week, the nephx foetuses were significantly hypoxic, but FP erythropoietin concentrations were not increased. Adrenocorticotropic hormone (ACTH) and cortisol concentrations, when measured on day 14, were not different between the two groups. Adrenocorticotropic hormone levels were correlated with adrenal weight at post‐mortem.4. Foetal plasma creatinine, magnesium and phosphate concentrations in nephx foetuses increased, eventually reaching values approximately twice that in controls. Foetal plasma chloride levels decreased continuously in nephx foetuses, eventually being 23 mmol/L lower than controls. Maternal plasma composition was unchanged.5. Total foetal fluid (amniotic + allantoic) volumes were reduced when measured at post‐mortem on day 14 after nephx. The composition of both fluids was significantly altered in the nephx foetuses compared with controls.6. Fetuses can survive in utero for 2 weeks after bilateral nephrectomy. However, there are multiple changes in plasma composition that may compromise foetal survival in the long term.
Effect Of Uranyl Nitrate‐Induced Renal Failure On Morphine Disposition And Antinociceptive Response In Rats
Authors: Crugten Jacoba T Van , Nation Roger L 
Published: March 2003

SUMMARY1. The aims of the present study were to administer morphine (14.0 μmol/kg, s.c.) to male Hooded Wistar rats and to determine the effect of uranyl nitrate‐induced renal failure on: (i) the antinociceptive effect of morphine; (ii) the pharmacokinetics of morphine and morphine‐3‐glucuronide (M3G); and (iii) the relationship between antinociceptive effect and the pharmacokinetics of morphine in plasma and brain.2. Renal failure was induced by a single s.c. injection of uranyl nitrate and kinetic/dynamic studies were performed 10 days after its administration, when creatinine clearance was 17% of the control group. Antinociceptive effect was measured by the tail‐flick method at various times up to 2 h post‐drug administration. Concentrations of morphine and M3G in plasma and brain and concentrations of creatinine in urine and serum were determined by specific HPLC methods.3. After morphine administration, the area under the antinociceptive effect–time curve was decreased by 44% in renal failure rats. There were no differences between control and renal failure rats in: (i) plasma morphine concentration–time curves; (ii) brain morphine concentration–time curves; and (iii) plasma M3G concentration–time curves. Morphine‐6‐glucuronide was not detected in any plasma or brain sample from rats administered morphine and no M3G was detected in brain.4. For both control and renal failure rats, the relationships between antinociceptive effect and plasma morphine concentration were characterized by counterclockwise hysteresis loops, probably reflecting a delay for the relatively polar morphine to cross the blood–brain barrier. The relationship between antinociceptive effect and brain morphine concentration in control rats revealed no evidence of acute tolerance and was described by a sigmoidal function. In contrast, the relationship in renal failure rats was characterized by clockwise hysteresis, which is consistent with acute tolerance development.
Congenic Rats For Hypertension: How Useful Are They For The Hunting Of Hypertension Genes?
Authors: Nabika Toru , Kobayashi Yuta , Yamori Yukio 
Published: March 2003

SUMMARY1. Linkage studies have revealed quantitative trait loci (QTL) for blood pressure in the rat genome using genetic hypertensive rat models. To identify the genes responsible for hypertension, the construction of congenic rats is essential.2. To date, several congenic strains have been obtained from spontaneously hypertensive or Dahl salt‐sensitive rats. The results of these studies should be interpreted according to whether the rats carry the whole QTL region or not.3. After establishing congenic strains, three strategies are possible: (i) an orthodox positional cloning in which, using subcongenic strains, the QTL region is cut down to smaller fragments suitable for physical mapping; (ii) a positional candidate strategy in which candidate genes in the QTL regions are studied; or (iii) physiological studies in which intermediate phenotypes directly associated with the hypertension gene are explored. Several other experimental strategies are also available using congenic strains as new animal models for hypertension.4. To make the most of advances in DNA technology, the precise evaluation of the phenotypic difference between congenic strains carrying different QTL or between a congenic and parental strain is critical.
Greater Blood Pressure‐Lowering Effect Of The Renin Inhibitor EMD 58265 Than An Angiotensin‐Converting Enzyme Inhibitor In Two‐Kidney One‐Clip Goldblatt Rabbit
Authors: Zimmerman Ben G 
Published: March 2003

SUMMARY1. Renin inhibitors may be more advantageous than either angiotensin‐converting enzyme (ACE) inhibitors or angiotensin (Ang) antagonists in blocking the renin–angiotensin system (RAS) because they do not allow accumulation of either AngI or AngII in plasma.2. Effects of i.v. administration of two human renin inhibitors (EMD 58265 and U 71038) were compared with the ACE inhibitor enalaprilat on mean blood pressure (BP), renal blood flow (RBF) and plasma AngI and AngII in the anaesthetized two‐kidney one‐clip Goldblatt rabbit.3. At doses of 2–2.5 mg/kg, i.v., EMD 58265 and 5–10 mg/kg, i.v., U 71038, both drugs decreased BP approximately 10 mmHg more than enalaprilat (2–4 mg/kg, i.v.) when given either before or after the ACE inhibitor. None of the three agents had any significant effect on RBF in the face of the lowered BP; however, renal vascular resistance was decreased. A higher dose of enalaprilat (10 mg/kg, i.v.) had no further effect on BP than the lower doses but did cause a marked increase in RBF.4. Both renin inhibitors markedly decreased plasma AngI, but the high basal level of AngII was less consistently and only modestly affected. Enalaprilat, in either the low dose range or at the high dose, was also not effective in significantly decreasing AngII.5. The results indicate that renin inhibition in the rabbit with a high circulating AngII level is more effective in lowering BP than ACE inhibition. A high dose of the ACE inhibitor may be required to block the intrarenal RAS, which may account for the increase in RBF.
Calcium‐Activated Potassium Currents In Mammalian Neurons
Authors: Sah Pankaj , Davies Phil 
Published: March 2003

SUMMARY1. Influx of calcium via voltage‐dependent calcium channels during the action potential leads to increases in cytosolic calcium that can initiate a number of physiological processes. One of these is the activation of potassium currents on the plasmalemma. These calcium‐activated potassium currents contribute to action potential repolarization and are largely responsible for the phenomenon of spike frequency adaptation. This refers to the progressive slowing of the frequency of discharge of action potentials during sustained injection of depolarizing current. In some cell types, this adaptation is so marked that despite the presence of depolarizing current, only a single spike (or a few spikes) is initiated. Following cessation of current injection, slow deactivation of calcium‐activated potassium currents is also responsible for the prolonged hyperpolarization that often follows.2. A number of macroscopic calcium‐activated potassium currents that can be separated on the basis of kinetic and pharmacological criteria have been described in mammalian neurons. At the single channel level, several types of calcium‐activated potassium channels also have been characterized. While for some macroscopic currents the underlying single channels have been unambiguously defined, for other currents the identity of the underlying channels is not clear.3. In the present review we describe the properties of the known types of calcium‐activated potassium currents in mammalian neurons and indicate the relationship between macroscopic currents and particular single channels.
Extrarenal Renin–Angiotensin Systems Are Unable To Maintain Blood Pressure In Sheep
Authors: Bonnet Jeanne‐Marie , Boivin Robert , Bernard Nicole , Sassard Jean 
Published: March 2003

SUMMARY1. The present study was designed to assess the participation of extrarenal tissue renin–angiotensin systems (RAS) in pressure homeostasis in sheep.2. The effect of the administration of an angiotensin II type 1 receptor antagonist (losartan; 30 mg/kg, i.v.) on mean arterial blood pressure (MABP) was investigated in eight intact (controls) and 10 binephrectomized sheep haemodialysed every 2 days for 10 days.3. In control sheep, losartan decreased blood pressure and this decrease was significantly more marked after furosemide‐induced water and salt depletion. After nephrectomy and throughout the anephric period, losartan lost its hypotensive effect, while the plasma renin concentration fell to undetectable levels. Baseline MABP became significantly lower than at the beginning of the anephric period after 7 days. The inability to maintain blood pressure after several volume‐depleting haemodialysis sessions proved that an efficient system for blood pressure regulation was lacking after nephrectomy.4. Renin gene expression measured by reverse transcription– polymerase chain reaction was found in liver, adrenal and arterial wall tissue. Neither nephrectomy nor sodium depletion enhanced this tissue renin gene expression.5. In conclusion, the present work allows us to exclude an active role of extrarenal RAS in the maintenance of blood pressure. In addition, haemodialysis technology in nephrectomized sheep can be used as a good model for the study of extrarenal control of blood pressure.