bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONCENTRATION‐EFFECT RELATIONSHIPS OF MORPHINE AND MORPHINE‐6β‐GLUCURONIDE IN THE RAT
Authors: van Crugten Jacoba T. , Somogyi Andrew A. , Nation Roger L. , Reynolds Geoffrey 
Published: June 2007

SUMMARY1. The aims of the present study were to determine the relationship between the antinociceptive effect and concentrations of morphine and morphine‐6β‐glucuronide (M6G) in plasma and in the brain.2. Morphine (14.0 and 28.0 μ‐mol/kg) or M6G (8.67 and 17.3 μmol/kg) were administered s.c. to male Hooded‐Wistar rats. The antinociceptive effect was measured by the thermal tail‐flick method at various times up to 2 h and concentrations of morphine, morphine‐3β‐glucuronide (M3G) and M6G in plasma and in the brain were determined.3. With a two‐fold increment in morphine dose, the areas under the antinociceptive effect‐, plasma morphine concentration‐ and brain morphine concentration‐time curves increased by 1.9‐, 2.3‐ and 2.3‐fold, respectively. The area under the plasma M3G concentration‐time curve increased 2.7‐fold. Morphine‐6β‐glucuronide was not detected in any sample. For M6G, doubling of the dose led to a 1.7‐fold increase in the area under the curve for plasma‐time M6G concentrations but an 8.7‐fold increase in the area under the curve for the antinociception‐time effect. Concentrations of M6G in the brain were below the limit of quantification. The relationship between antinociceptive effect and plasma morphine or M6G were characterized by counterclockwise hysteresis loops, probably reflecting a delay in crossing the blood‐brain barrier.4. Morphine‐6β‐glucuronide was approximately equipotent to morphine on the basis of dose, but substantially more potent on the basis of brain concentration.
NITRIC OXIDE SYNTHASE INHIBITION WITH Nω‐NITRO‐L‐ ARGININE METHYL ESTER AFFECTS BLOOD PRESSURE AND CARDIOVASCULAR STRUCTURE IN THE GENETICALLY HYPERTENSIVE RAT STRAIN
Authors: Ledingham Janet M. , Laverty R. 
Published: June 2007

SUMMARY1. Inhibition of nitric oxide (NO) synthesis with the nitric oxide synthase (NOS) inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME) was used as a tool to investigate further a possible endothelial defect in the New Zealand genetically hypertensive (GH) rat strain compared with its normotensive (N) control strain.2. Nω‐nitro‐L‐arginine methyl ester was given to GH and N groups in their drinking water from age 7–10 weeks (10 mg/kg per day for weeks 1 and 2 and then 5 mg/kg per day for week 3). Tail‐cuff blood pressure (BP) was measured weekly and at the end of the experiment the mesentery was fixed by perfusion, second order branches of the mesenteric artery were embedded in Technovit and stained sections were used to quantify the structure of the mesenteric resistance arteries (MRA). The heart was removed and weighed for determination of left ventricular (LV) mass.3. In GH rats, BP and LV mass were significantly raised by L‐NAME, while in N rats L‐NAME treatment significantly elevated BP, but had no effect on LV mass.4. In GH rats, the media width was significantly increased by L‐NAME treatment (P < 0.01) lumen diameter remained unchanged. Thus, the ratio of media width/lumen diameter (M/L) was significantly increased by exacerbation of the hypertrophic outward remodelling characteristic of the GH strain. There were no significant changes in the M/L ratio in L ‐NAME‐treated N rats.5. Thus, in the GH strain, cardiovascular structure is more sensitive to NOS inhibition than either its N control strain or (on evidence from the literature) the spontaneously hypertensive rat strain.
ACUTE BUT NOT CHRONIC ANGIOTENSIN‐CONVERTING ENZYME INHIBITION INDUCES ENZYME SYNTHESIS IN THE GLOMERULUS OF THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Hodge G. , Makarious MM , Charlesworth JA , Duggan KA 
Published: June 2007

SUMMARY1. Treatment with angiotensin‐converting enzyme (ACE) inhibitors slows the rate of progression of nephropathy in the spontaneously hypertensive rat (SHR) with streptozotocin‐induced diabetes. Paradoxically, however, chronic ACE inhibitor therapy has been reported to be associated with induction of ACE in the plasma. We sought to determine whether induction also occurred in the glomerulus.2. Seven days after induction of diabetes rats were randomized to receive perindopril (4mg/kg per day) in the drinking water or water alone. Blood glucoses were maintained 6–10 mmol/L by daily ultralente insulin. Rats were killed after 1 and 12 weeks of ACE inhibitor therapy and the kidneys were harvested. Angiotensin‐converting enzyme activity was determined in isolated glomeruli before and after removal of perindopril and reconstitution with zinc sulphate.3. After 1 week of ACE inhibitor therapy, glomerular ACE was significantly greater after removal of perindopril than either before its removal (P < 0.025) or in the untreated controls (P < 0.025). After 12 weeks of therapy, ACE activity was significantly lower in the perindopril‐treated group than in the untreated controls (P < 0.025). There was no increase in ACE activity following removal of perindopril.4. These studies suggest that short‐term ACE inhibition is associated with induction of ACE in the glomerulus. However, there was no increase in ACE activity after removal of perindopril, suggesting that induction of synthesis of this enzyme in the glomerulus does not occur during chronic ACE inhibition.
INFLUENCE OF MUSCLE BLOOD FLOW ON FATIGUE DURING INTERMITTENT HUMAN HAND‐GRIP EXERCISE AND RECOVERY
Authors: Pitcher Julia B. , Miles Timothy S. 
Published: June 2007

SUMMARY1. The influence of muscle blood flow on fatigue and recovery was studied in the forearm muscles of eight male subjects performing a powerful isometric hand‐grip exercise. The exercise was performed with the exercising forearm normally perfused and, on a separate occasion, with its blood flow occluded with a sphygmomanometer cuff.2. In the no cuff condition, peak force declined to an initial plateau at 40–50% of the maximal voluntary grip force (MVC). When perfusion was occluded, the force decline was similar during the first minute of exercise, then force fell rapidly to exhaustion.3. In a separate experiment to investigate the mechanisms underlying the plateau in force loss, occlusion of blood flow during the force plateau phase resulted in a rapid decline in force to exhaustion.4. Recovery of peak force after the cuff exercise was significantly greater during the initial 3.5 min of recovery than after no‐cuff exercise. After this time, recovery was similar for both conditions.5. Muscle blood flow occlusion during intermittent exercise profoundly reduces endurance without prolonging recovery. Recovery time may depend on the duration and energy cost of the exercise rather than on the degree of force loss.6. The present study suggests that the fall in muscle force induced by a continuous MVC is a combination of profound short‐term fatigue in anaerobic muscle fibres due to the consumption of their short‐term energy supplies, plus a decline in force production by aerobic muscle fibres that is the consequence of hypoxia. Thus, MVC may not be a good model of fatigue occurring under submaximal conditions, as hypoxia of type I fibres is unlikely to occur under physiological conditions in which muscle contractions are usually intermittent.
COMPONENTS OF THE BLOOD ACID‐BASE DISTURBANCE THAT ACCOMPANIES URETHANE ANAESTHESIA IN RATS DURING NORMOTHERMIA AND HYPOTHERMIA
Authors: Alfaro V. , Palacios L. 
Published: June 2007

SUMMARY1. We have studied the components of the metabolic acidosis that accompanies urethane anaesthesia in rats, both with and without the hypothermia that results from this anaesthesia.2. Acid‐base disturbances were analysed with an approach based on Stewart's analysis of acid‐base chemistry.3. The pH fall in the blood of normothermic anaesthetized rats (body temperature Tb) = 37°C) was related to increases in plasma anions (lactate and [Cl−]), which decreased the strong ion difference ([SID]), as well as to increase the weak acid buffers due to increases in albumin.4. A stronger metabolic acidosis was found in the blood of rats with hypothermia induced by urethane (Tb= 32°C). Although plasma lactate was unchanged in hypothermic rats, [SID] decreased due to alterations in the plasma ionic balance. The metabolic acidosis found in hypothermia was also associated with increased weak acid buffers due to increases in albumin and inorganic phosphate. Further to hyperphosphataemia, signs of acute renal disfunction, such as increases in plasma [Mg2+] and blood urea nitrogen were found. Plasma retention of endogenous acids together with the retention of acid end‐products of the metabolism of urethane because of acute renal failure may have contributed to strengthening the fall in pH and [HCO3−] found in urethane‐induced hypothermic rats.
MEMBRANE AND SECRETORY PROPERTIES OF RENAL JUXTAGLOMERULAR GRANULAR CELLS
Authors: Kurtz Armin 
Published: June 2007

SUMMARY1. The control of renin secretion from renal juxtaglomerular granular cells on the cellular level is not yet completely understood.2. There is evidence that calcium‐ and cyclic nucleotide‐related pathways exert an opposite control of renin secretion.3. There is accumulating evidence that the electrical properties of juxtaglomerular cells are important for the regulation of renin secretion.
PHARMACOLOGICAL ACTION OF AUSTRALIAN ANIMAL VENOMS
Authors: Hodgson Wayne C. 
Published: June 2007

SUMMARY1. Australia has some of the most venomous fauna in the world. Although humans are not usually perceived as being predators against these animals they are often envenomated, accidentally or otherwise. This has led to the development of antivenoms against some of the potentially lethal venoms. However, further understanding of the mechanism(s) of action of these and other venoms is important, not only for developing new treatment strategies but also in the search for novel research tools.2. The present review discusses the pharmacology of some of the components found in venoms and outlines the research undertaken on some of Australia's venomous animals, with the exception of snakes.3. Biogenic amines, peptides and enzymes are common venom components and produce a wide range of effects in envenomated humans. For example, respiratory failure observed after envenomation by the box jellyfish (Chironex fleckeri) and Sydney funnel‐web spider (Atrax robustus) is most likely due to potent neurotoxins in the venoms. Stonefish (Synanceja trachynis) and platypus (Ornithorhynchus anatinus) venoms, although not considered lethal, cause severe pain. However, the components responsible for these effects have not been isolated. Venom components, as yet unidentified, may be responsible for the cutaneous necrotic lesions that have been reported after some spider bites (e.g. Lampona cylindrata). Other venoms, such as those of the jumper ant (Myrmecia pilosula) and bull ant (M. pyriformis), may produce only mild skin irritation to the majority of humans but a severe anaphylactic response in sensitized victims.4. While there has been a renewed interest in toxinology, further research is required to fully elucidate the pharmacological action of many of these venoms.
DIFFERENTIAL REGULATION OF NATRIURETIC PEPTIDE GENES IN INFARCTED RAT HEARTS
Authors: Shimoike Hitoshi , Iwai Naoharu , Kinoshita Masahiko 
Published: June 2007

SUMMARY1. We investigated the regulation of the atrial natriuretic peptide and brain natriuretic peptide genes in a rat model of myocardial infarction induced by isoproterenol (IP rat) and in a rat model of cardiac hypertrophy induced by aorto‐caval shunt (AC shunt rat).2. Brain natriuretic peptide (BNP) mRNA levels in atria were significantly higher in IP rats than in controls at 18 h after the administration of isoproterenol, but no significant increases were observed in atrial natriuretic peptide (ANP) mRNA expression levels at any time point examined. In the ventricles, the BNP mRNA levels peaked at 18 h after isoproterenol administration, whereas ANP mRNA levels gradually increased until 3 days after isoproterenol administration.3. The BNP mRNA levels in both atria and ventricles were significantly increased at 1 day after the introduction of aorto‐caval shunt, while the ANP mRNA levels were not.4. Plasma BNP levels were closely correlated with left ventricular weight per bodyweight, in both IP rats and AC shunt rats.5. These results suggest the differential regulation of ANP and BNP genes in both the atria and ventricles in these two pathological models.
THE SYMPATHETIC NERVOUS SYSTEM AND LONG‐TERM REGULATION OF ARTERIAL PRESSURE: WHAT ARE THE CRITICAL QUESTIONS?
Authors: Osborn John W. 
Published: June 2007

SUMMARY1. The role of the sympathetic nervous system in long‐term control of arterial pressure remains unclear despite decades of intense research.2. Previous studies have shown that denervation of arterial baroreceptors does not chronically increase arterial pressure. As baroreceptors are thought to provide the primary ‘error signal’ to the autonomic nervous system, this has been interpreted as evidence against neural control of arterial pressure over long periods of time.3. The possibility that other ‘error signals’ are important in the long‐term control of sympathetic activity (and arterial pressure) is introduced.4. The following ‘Critical Questions’ are presented for subsequent discussion: (i) is the sympathetic nervous system a ‘major player’ in the long‐term control of arterial pressure; (ii) why doesn't arterial pressure remain at hypertensive levels after arterial baroreceptor denervation; and (iii) which ‘error signals’ are most important in the long‐term control of sympathetic outflow?
INTERACTIONS BETWEEN VASOPRESSIN AND BAROREFLEX CONTROL OF THE SYMPATHETIC NERVOUS SYSTEM
Authors: Hasser Eileen M. , Bishop Vernon S. , Hay Meredith 
Published: June 2007

SUMMARY1. In addition to its effects at the renal tubules to influence water retention and at vascular smooth muscle to cause vasoconstriction, the hormone arginine vasopressin also appears to modulate cardiovascular reflex control of the sympathetic nervous system. Infusion or endogenous release of vasopressin results in enhanced baroreflex sympatho‐inhibitory responses compared with other pressor agents. In addition, when changes in arterial pressure are imposed on an elevated background level of circulating vasopressin, due either to infusion or endogenous release, the arterial baroreflex response is shifted to lower pressures, and the maximum sympatho‐excitation to a decrease in pressure is reduced.2. Evidence suggests that vasopressin may influence cardiovascular reflex function at multiple sites. Nevertheless, the primary site involved in the effects of circulating vasopressin on baroreflex function appears to be in the central nervous system, specifically in the area postrema. Lesion of the area postrema abolishes the ability of circulating vasopressin to modulate arterial baroreflex and cardiopulmonary reflex function and electrical or chemical stimulation of this circum‐ventricular organ mimics the effects of vasopressin. In addition, vasopressin has been shown to influence the activity of area postrema neurons in vivo and in vitro. Although not all studies agree, the effects of the area postrema and vasopressin on cardiovascular reflex function appear to be dependent on afferent input from peripheral baroreceptors.3. Most evidence suggests that vasopressin exerts its effects on baroreflex function through a V1 vasopressin receptor mechanism. Systemic administration or microinjection into the area postrema of a specific V1 receptor antagonist abolishes the action of arginine vasopressin on arterial baroreflex and cardiopulmonary reflex control of the sympathetic nervous system.4. The ability of vasopressin and the area postrema to influence baroreflex function appears to be dependent on an α2‐adrenoceptor mechanism at the level of the nucleus tractus solitarius (NTS). Blockade of α2‐adrenoceptors in the NTS abolishes the effects of vasopressin and the area postrema on the sympathetic nervous system. Facilitation of NTS processing of baroreceptor afferent inputs by the area postrema could contribute to the enhanced sympatho‐inhibition and shift of the baroreflex curve to lower pressures during elevations in circulating vasopressin.
NEURAL CONTROL OF MUSCLE BLOOD FLOW: IMPORTANCE DURING DYNAMIC EXERCISE
Authors: Rowell Loring B. 
Published: June 2007

SUMMARY1. The present review examines the control of muscle vascular conductance by the sympathetic nervous system during exercise.2. Evidence for tonic sympathetic neural control of active muscle rests on three findings: (i) directly measured muscle sympathetic nerve traffic is increased; (ii) spillover of noradrenaline from active muscles is also increased; and (iii) withdrawal of sympathetic outflow to active muscle either by acute blockade of its sympathetic nerve supply or by reflex inhibition of sympathetic nervous activity raises muscle vascular conductance via inhibition of tonic vasoconstriction.3. Loss of tonic sympathetic control of muscle vascular conductance during mild to severe exercise causes marked hypotension despite maintenance of a normal cardiac output.4. The extent to which active muscle can vasodilate in intact animals appears to have been hidden by tonic vasoconstriction. This vasoconstriction appears to be minimally affected by metabolites in oxidative (red) muscle, but may be inhibited in predominantly glycolytic (white) muscle owing to different spatial distributions of α‐ and α2‐adrenoceptors in the two muscle types and to the different susceptibilities of the two receptor types to interference by metabolites.5. The reflexes causing vasoconstriction in active and inactive muscles are unknown. One hypothesis is that a flow‐sensitive muscle chemoreflex raises sympathetic outflow to reduce accumulations of muscle metabolites caused by mismatches between muscle blood flow and metabolism, called ‘flow errors’. Another hypothesis is that the arterial baroreflex corrects mismatches between cardiac output and vascular conductance called ‘pressure errors’. This review argues for a dominance of control by the baroreflex based on the following observations: (i) the arterial baroreflex is essential to the normal rise in sympathetic nervous activity and arterial pressure at the onset of exercise; (ii) during submaximal exercise, a functioning arterial baroreflex is required to maintain tonic sympathetic activity and prevent arterial hypotension; and (iii) whereas a muscle chemoreflex may be needed to guard against hypoperfusion of active muscle, the arterial baroreflex must oppose hypotension by initiating sympathetic vasoconstriction to oppose muscle vasodilation.
HYPOTENSIVE EFFECT OF CHRONICALLY INFUSED ADRENOMEDULLIN IN CONSCIOUS WISTAR‐KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Khan Azharul Islam , Kato Johji , Kitamura Kazuo , Kangawa Kenji , Eto Tanenao 
Published: June 2007

SUMMARY1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na+ and K+ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion.3. A significant reduction in SBP was observed in hAM‐treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM‐treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na+ excretion in hAM‐treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma hAM levels in treated WKY rats and SHR were 0.0 ± 9.4 and 0.6 ± 0.2 fmol/mL, respectively.4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na+ excretion at a plasma AM concentration within the physiological limit.
AUSTRALIAN COMPARATIVE OUTCOME TRIAL OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR‐ AND DIURETIC‐BASED TREATMENT OF HYPERTENSION IN THE ELDERLY (ANBP2): OBJECTIVES PROTOCOL
Authors: Reid C. M. 
Published: June 2007

SUMMARY1. ANBP2 is a comparative outcome trial of angiotensin‐converting enzyme inhibitor‐ and diuretic‐based treatment of hypertension in the elderly using a prospective randomized open‐label design with blinding of endpoint assessments.2. The primary objective is to determine, in hypertensive subjects 65–84 years of age, whether there is any difference in total cardiovascular events (fatal and non‐fatal) over a 5 year treatment period between the two treatment regimens.3. The study is being conducted in general practices throughout Australia and will recruit 6000 subjects over 2–3 years (3000 in each arm of the study) to provide 30000 years of patient observation. This will allow detection of a 25% difference in the primary outcome variable at the 5% level with a power of 90%.4. Following randomization to one of the treatment arms, each subject's blood pressure (BP) is managed by the general practitioner according to his/her usual practice to achieve goal BP with guidelines for drug therapy relevant to each treatment arm.5. Study endpoint information is gained from a review of practice records every 3 months and these data are then assessed by an Endpoint Committee blinded for treatment randomization.6. Interim analyses of endpoint data will be conducted at the end of randomization and then annually until the final analysis after 5 years of observation in each subject.
MECHANISM OF THE POTENTIATION OF VASOCONSTRICTION BY NEUROPEPTIDE Y IN ARTERIOLES FROM THE SUBMUCOSA OF THE GUINEA‐PIG SMALL INTESTINE
Authors: Neild TO , Xia J. 
Published: June 2007

SUMMARY1. Neuropeptide Y (NPY; 3–100 nmol/L) caused a concentration‐dependent potentiation of constriction in response to noradrenaline or the thromboxane mimetic U46619 in arterioles from the submucosa of the guinea‐pig small intestine.2. In arterioles permeabilized by exposure to the α‐toxin of Staphylococcus aureus and maintained in Ca2+‐buff'ered medium, NPY potentiated the contractile effects of Ca2+. The magnitude of the potentiation was the same as in intact arterioles.3. Exposure of arterioles to 1 μmol/L nifedipine to inhibit Ca2+influx or to 20 μmol/L cyclopiazonic acid to abolish Ca2+ uptake into internal stores had no effect on the potentiating action of NPY.