bluuebunny/crossref_metadata_2025_split huggingface dataset:
TACHYKININ RECEPTORS MEDIATING NON‐CHOLINERGIC CONTRACTION OF THE GUINEA‐PIG ISOLATED MAIN BRONCHUS IN RESPONSE TO FIELD STIMULATION
Authors: Heavey Melanie L. , Lau Winnie AK , Pennefather Jocelyn N. 
Published: June 2007

SUMMARY1. The primary aim of the present study was to classify the receptors activated by tachykinins released by field stimulation of intramural nerve terminals of the guinea‐pig isolated main bronchus by using the novel non‐peptide NKi and NK2 receptor‐selective antagonists SR140333 and SR 48968, respectively.2. Log concentration‐response curves to substance P (SP), the NKi receptor‐selective agonist [Sar9, Met(O2)11]‐SP and the NK2receptor‐selective agonist [Nle10]‐neurokinin (NK) A(4‐10) were constructed in the presence of indomethacin (2 μmol/L) and phosphoramidon (5 (μmol/L). Substance P was the least potent of these agonists.3. In left and right main bronchi, SR 140333 (lOOnmol/L) antagonized concentration‐related contractions evoked by SP yielding pKB values of 8.02 and 7.68, respectively. SR 140333 (10 nmol/L) antagonized the effects of [Sar9, Met(O2)11]‐SP on the left bronchus with a pKB value of 8.04.4. SR 48968 (100 nmol/L) antagonized the effects of SP yielding pKB estimates of 7.88 (left bronchus) and 731 (right bronchus).5. [Nle10]‐NKA(4‐10) was more potent in the left than in the right main bronchus. SR 48968 (0.1‐10 nmol/L) antagonized the effects of [NleI0]‐NKA(4‐10) on the left bronchus with pKBestimates of 8.26‐10.25.6. In the presence of indomethacin (2 μmol/L), phosphoramidon (5 μmol/L) and atropine (1 (μmol/L), electrical field stimulation (EFS; 30 V, 1ms, 15 s at 1, 3, 10 and 30 Hz) produced prolonged contractions. SR 48968 (0.1 μmol/L) markedly reduced responses to stimulation, whereas SR 140333 (0.3 μmol/L) caused a small but significant rightward displacement of the log frequency‐response curve. In combination, these concentrations of SR 48968 and SR 140333 produced complete inhibition to field stimulation at 10 Hz.7. These results indicate that: (i) both NK1 and NK2 receptor subtypes are present in the guinea‐pig main bronchi with the left bronchus being more sensitive to an NK2 receptor agonist; and (ii) EFS of the main bronchus leads to frequency dependent contractions due to the release of tachykinin(s) that predominantly activate an NK2 receptor.
AN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR PROTECTS AGAINST DOXORUBICIN‐INDUCED IMPAIRMENT OF CALCIUM HANDLING IN NEONATAL RAT CARDIAC MYOCYTES
Authors: Maeda Atsuyoshi , Honda Masaaki , Kuramochi Takehiko , Tanaka Koichi , Takabatake Toshikazu 
Published: June 2007

SUMMARY1. The effects of doxorubicin (DOX) on intracellular calcium transients were examined in neonatal rat cultured cardiac myocytes, as were the cardioprotective effects of an angiotensin‐converting enzyme (ACE) inhibitor on DOX‐induced impairment of calcium handling.2. Cultured cardiac myocytes isolated from neonatal Wistar‐Kyoto rats were treated with DOX for 24 h. Field‐stimulated calcium transients in single myocytes were measured in the presence or in the absence of isoproterenol using fura‐2/AM. Calcium transients were also measured after the addition of DOX to myocytes pretreated with M‐I (an active metabolite of delapril HC1, an ACE inhibitor.3. Doxorubicin reduced the amplitude and maximum velocity of increase and decrease of calcium transients, prolonged the time‐course of calcium transients and impaired the β‐adrenoceptor responsiveness of calcium transients in a dose‐dependent manner. The DOX‐induced impairment of calcium transients and (5‐adrenoceptor responsiveness was improved by M‐I.4. Doxorubicin impaired both the mobilization and sequestration of intracellular calcium ions in contraction‐relaxation cycles and the response of calcium transients to (3‐adrenocep‐tor stimulation. The ACE inhibitor ameliorated DOX‐induced impairment of calcium dynamics, suggesting that M‐I, an active metabolite of delapril, protects against DOX‐induced abnormal calcium handling leading to cardiac dysfunction.
PURINES AND THE NUCLEUS TRACTUS SOLITARIUS: EFFECTS ON CARDIOVASCULAR AND RESPIRATORY FUNCTION
Authors: Phillis JW , Scislo TJ , O'Leary DS 
Published: June 2007

SUMMARY1. The roles of adenosine and adenosine 5′‐triphosphate in cardiorespiratory regulation by the nucleus tractus solitarius (NTS) have been evaluated in a range of experiments, using microinjections of selective agonists and antagonists of purinoceptors.2. Adenosine injected into the caudal NTS decreases heart rate (HR), arterial blood pressure (BP) and respiratory frequency by an action at A2a receptors on glutamatergic nerve terminals. Microinjections of the A2a agonist CGS 21680 caused falls in arterial BPand HR which were selectively antagonized by the A2a antagonist CGS 15943. Injection of the Ai agonist CPA in the caudal NTS elevated BP and HR and its actions were selectively antagonized by the Ai antagonist l,3‐dipropyl‐8‐cyclopentylxan‐thine. Adenosine enhanced glutamate release in the NTS.3. In the rostral NTS, adenosine administration resulted in an elevation of BP.4. ATP microinjection into the subpostremal NTS depressed HR and BP by an action on P2x purinoceptors, which are blocked by suramin. ATP microinjections differentially affected vascular conductance in regional peripheral vascular beds, with the most marked increases in conductance in the iliac bed and lesser effects in the superior mesenteric and renal vascular beds.5. Recordings from renal and lumbar sympathetic nerves have demonstrated marked dose‐dependent decreases in efferent activity following α, β‐methylene ATP injections into the NTS; however, only renal but not lumbar sympathetic nerve activity was inhibited following CGS 21680 injections into the same site of the NTS.6. ATP may function as a fast‐acting neurotransmitter in the baroreceptor afferent pathway or in interneurons in the NTS. Adenosine is likely to play a role as a modulator of activity in baroreceptor and chemoreceptor pathways, fine tuning the functional output of both systems.
CENTRAL NERVOUS SYSTEM CONTROL OF CARDIOVASCULAR FUNCTION: NEURAL MECHANISMS AND NOVEL MODULATORS
Authors: Spyer KM , Lambert JH St , Thomas T. 
Published: June 2007

SUMMARY1. Studies are described that indicate that hypothalamic stimulation, at sites eliciting the defence reaction, results in an increase in adenosine levels in both the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) of the rat.2. Adenosine receptor antagonists applied to these sites attenuate the pressor response elicited by hypothalamic stimulation. Adenosine appears to be produced extracellularly from ATP, which is released from axon terminals in both the NTS and RVLM.3. The implications of these observations for the pharmacology of hypothalamic actions on reflex inputs that modify cardiorespiratory function are discussed.
PATHOGENESIS OF THE INSULIN RESISTANCE SYNDROME (SYNDROME X)
Authors: Chisholm Donald J. , Campbell Lesley V. , Kraegen Edward W. 
Published: June 2007

SUMMARY1. Insulin resistance is an early and major feature in the development of non‐insulin‐dependent diabetes mellitus (NIDDM), but it is also associated with hyperlipidaemia, hypertension, obesity and cardiovascular disease, the so‐called ‘insulin‐resistance syndrome’ (Syndrome X).2. There is a strong genetic determination of NIDDM and insulin resistance, but the environmental factors of calorie excess, reduced activity and obesity also make a major contribution.3. Central (abdominal) obesity is much more strongly associated with insulin resistance than is overall obesity. From twin studies, there appears to be specific genetic determinants of central abdominal fat, independent of overall obesity.4. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Isocaloric alteration of macro‐nutrients substantially affects insulin sensitivity in rats but not, at least in the short‐term, in humans.5. Exercise training improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat.6. Metformin has been the only available drug that has been used clinically to significantly improve insulin sensitivity, but the new ‘glitazones’ (thiazolidinediones) have a more specific effect via altered lipid metabolism.
DIABETIC RETINOPATHY: EARLY FUNCTIONAL CHANGES
Authors: Alder Valerie A. , Su Er‐Ning , Yu Dao‐Yi , Cringle Stephen J. , Yu Paula K. 
Published: June 2007

SUMMARY1. The present review reports some of the earliest physiological changes that occur in the diabetic retina prior to any clinical or anatomical changes in an animal model of diabetes.2. Using chemically induced diabetes (by streptozotocin) in rats, retinal blood flow and vitreal and retinal oxygen tension were determined after 5 weeks of sustained hyperglycaemia. Blood flow was greater and was also redistributed in the diabetic group compared with values for the control group. At the same time, oxygen tension distribution was altered around retinal arterioles, implying an increase in retinal oxygen consumption in these early diabetic retinas.3. The possibility that the blood flow changes could be due to altered control mechanisms in the retinal vasculature was confirmed using an isolated, perfused eye preparation. In diabetic eyes an altered reactivity to test pharmacological agents was demonstrated after 4 weeks of diabetes.4. To further explore these vascular response changes we developed an isolated, perfused retinal arteriolar preparation in which individual segments of the vasculature can be tested. The possibility that insulin has a direct vasodilator effect on retinal arterioles was confirmed and was demonstrated to act via nitric oxide released from the vascular endothelial cells. These data may implicate the diabetic‐induced insulin changes in early retinal changes.5. Evidence is presented that although early glucose control may be vital in stopping the onset of diabetic retinopathy, there comes a stage in the induced diabetic cascade where if the retinopathy has commenced, good glucose control cannot stop the further progression of the retinopathy.
COMPARISON OF THE EFFECTS OF OUABAIN AND BRAIN NATRIURETIC PEPTIDE IN SALINE‐LOADED SHEEP
Authors: Pidgeon Grant B. , Richards A Mark , Nicholls M Gary , Lewis Lynley K. , Yandle Timothy G. , Rademaker Miriam T. , Charles Christopher J. , Bailey Ross R. , Lynn Kelvin L. 
Published: June 2007

SUMMARY1. It has been claimed that ouabain is an endogenous hormone that may be pivotal in the pathogenesis of some forms of hypertension and may exaggerate natriuresis in situations characterized by volume overload. We compared the haemodynamic, renal and endocrine effects of ouabain (at approximately 187 ng/kg per min for 2 h) with those of brain natriuretic peptide (BNP; at 5 pmol/kg per min for 2 h) in nine saline‐loaded sheep in a balanced, randomized, single‐blind, placebo‐controlled crossover study.2. Brain natriuretic peptide infusion reduced mean arterial pressure whereas ouabain infusion caused no change. Haematocrit rose steadily during BNP infusion but fell during ouabain infusion. Neither ouabain nor BNP affected urine volume, sodium, potassium or creatinine excretion. Mean heart rate declined during the ouabain and placebo infusions, but was not altered during BNP infusion. Endogenous ouabain concentrations were not detectable at baseline or during BNP or placebo infusions, but rose to concentrations of 11 ± 1.3 nmol/L during the ouabain infusion.3. These results suggest that ouabain is not an endogenous hormone present at physiologically relevant concentrations. Furthermore, ouabain does not cause natriuresis during saline‐loading in sheep and is therefore unlikely to be responsible for the exaggerated natriuresis seen in some forms of hypertension.
A STUDY OF NEUROKININS AND OTHER OEDEMA‐INDUCING MEDIATORS AND MECHANISMS IN THERMAL INJURY
Authors: Waller J , Siney L , Hoult JRS , Brain SD 
Published: June 2007

SUMMARY1. Mechanisms involved in the plasma extravasation observed following thermal injury of rat dorsal skin were investigated.2. Heat applied to the dorsal skin of anaesthetized rats by a temperature‐controlled skin heater (1 cm diameter) for 5 min induced temperature‐dependent plasma protein extravasation a. 48–48.5°C, measured for up to 4 h following initiation of heat.3. A tachykini. NK1 receptor antagonist (SR140333), a bradykinin B2 receptor antagonist (HOE 140) and a cyclooxygenase inhibitor (indomethacin), when given as cotreatments prior to the selected measurement period, markedly suppressed oedema formation observed over 0–1 h (P < 0.05) but not that observed over 3–4 h after injury.4. These results indicate that although neurokinins, bradykinin and cyclo‐oxygenase products may be important for the early response to thermal injury, they do not appear to play an important role in the ongoing oedem. response.5. Neutrophils accumulate at the inflammatory site by 4h after thermal injury. Therefore, the effect of depletion of circulating neutrophils by a rat anti‐neutrophil antiserum on oedema formation over the 0–4 h period was investigated. The results show that oedema formation was similar in control and antineutrophil‐treated rats.6. In conclusion, the data from the present study indicate that neuropeptides as well as other vasoactive mediators play a role in the acute plasma extravasation observed after thermal injury, but not in the ongoing inflammatory injury. Neutrophils, despite their presence at sites of thermal injury, do not appear to be involved in mediating the oedema formation observed up to 4 h after thermal injury.
PEROXYNITRITE: A MEDIATOR OF INCREASED MICROVASCULAR PERMEABILITY?
Authors: Greenacre S , Ridger V , Wilsoncroft P , Brain SD 
Published: June 2007

SUMMARY1. Increased expression of inducible nitric oxide synthase (iNOS) and subsequent elevation of nitric oxide (NO) levels at inflammatory sites have led to the suggestion that peroxynitrite (the reaction product of superoxide and NO) is involved in proinflammatory processes. The present study has investigated the ability of peroxynitrite to induce oedema formation in the rat cutaneous microvasculature.2. Peroxynitrite was synthesized from hydrogen peroxide and acidified nitrite. Spectrophotometry was used to measure the concentration and breakdown of peroxynitrite. It was also used to determine maximum amounts of hydrogen peroxide and sodium nitrite remaining after synthesis.3. Oedema formation in response to intradermall. (i.d.) injected peroxynitrite, hydrogen peroxide and sodium nitrite was measured by the extra vascular accumulation of i.v. [125I]‐albumin in the anaesthetized rat.4. Peroxynitrite (40,100 and 200 nmol/site) acted in a dose‐dependent manner to cause a mean (± SEM) increase in plasma extravasation of 24 ± 2,55 ± 5 and 69 ± 6 μL, respectivel. (n= 4), with resulting inflammatory oedema. Peroxynitrite induced significantly larger plasma extravasation than equivalent vehicle controls at doses of 100 (P > 0.05) and 200 nmol (P > 0.001). This increased extravasation appears to be a direct microvascular response to peroxynitrite administration and not due to either a raised pH, necessary to stabilize the peroxynitrite, or contaminating concentrations of hydrogen peroxide or sodium nitrite from which peroxynitrite is formed.5. These results suggest that peroxynitrite acts to increase microvascular permeability and oedema formation. Therefore, peroxynitrite may mediate vascular pro‐inflammatory effects in addition to its direct cytotoxic activity.
EFFECT OF DIETARY FAT REDUCTION AND INCREASED AEROBIC EXERCISE ON CARDIOVASCULAR RISK FACTORS
Authors: Nolte Leanne J. , Nowson Caryl A. , Dyke Ann C. 
Published: June 2007

SUMMARY1. The combined effect of dietary fat reduction and increased aerobic exercise on coronary heart disease (CHD) risk factors was investigated in healthy, normolipidaemic, normotensive, sedentary individuals.2. After a baseline period of 2 weeks, 21 subjects were randomly allocated to one of two intervention groups (low fat exercise (LFEX) or low fat control (LFQ) for 8 weeks. Both groups were counselled to reduce their dietary fat intake to 20–25% energy from fat. The LFEX group was also required to commence an aerobic exercise programme (4X45 min per week).3. In both groups, the falls in total cholesterol seen at week 4 were not maintained at the end of the study; however, the LFEX group maintained a fall in low‐density lipoprotein (LDL) o. 0.21±0.11 mmol/L. At the end of the study, the LFC group experienced a fall in high‐density lipoprotein (HDL)‐cholesterol of 0.16±0.05 mmol/L, due to a 0.19±0.07 mmol/L fall in the HDL2 subfraction. The LFEX group experienced no change in HDL (−0.09 ±0.06 mmol/L) or HDL2 (−0.09 ±0.05 mmol/L).4. At the end of the study the LFEX and LFC groups experienced a 7±3 and 5±lmmHg fall in systolic blood pressure, respectively, while the LFEX group also observed a 4±2 mmHg fall in diastolic bloo. pressure.5. The benefits of a low‐fat diet combined with aerobic exercise include a reduction in LDL and blood pressure, while maintaining HDL through th. HDL2 subfraction.
STRUCTURE AND FUNCTION OF URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASES
Authors: Meech Robyn , Mackenzie Peter I. 
Published: June 2007

SUMMARY1. The uridine diphosphate (UDP)‐glucuronosyltransferases (UGT) are a family of enzymes that catalyse the covalent addition of glucuronic acid to a wide range of lipophilic chemicals. They play a major role in the detoxification of many exogenous and endogenous compounds by generating products that are more polar and, thus, more readily excreted in bile or urine.2. Inherited deficiencies in UGT forms are deleterious, as exemplified by the debilitating effects of hyperbilirubinaemia and neurotoxicity in subjects with mutations in the enzyme that converts bilirubin to its more pola. glucuronide.3. The UGT protein can be conceptually divided into two domains with the amino‐terminal half of the protein demonstrating greater sequence divergence between isoforms. This region apparently determines aglycone specificity. The aglycone binding site is presumed to be a ‘loose’ fit, as many structurally diverse substrates can be bound by the same UGT isoform. The carboxyl‐terminal half, which is more conserved in sequence between different isoforms, is believed to contain a binding site for the cosubstrate UDP glucuronic acid (UDPGA).4. Uridine diphosphat. glucuronosyltransfera.se is localized to the endoplasmic reticulum (ER) and spans the membrane with a type I topology. The putative transmembrane domain is located near the carboxyl terminus of the protein such that only a small portion of the protein resides in the cytosol. This cytosolic tail is believed to contain an ER‐targeting signal. The major portion of the protein is located in the ER lumen, including the proposed substrate‐binding domains and the catalytic site.5. The microsomal membrane impedes the access of UDPGA to the active site, resulting in latency of UGT activity in intact ER‐derived microsomes. Active transport of UDPGA is believed to occur in hepatocytes, but the transport system has not been fully characterized. Uridine diphosphate glucuronosyltransfer‐ase activity is also highly lipid dependent and the enzyme may contain regions of membrane association in addition to the transmembrane domain.
MANAGEMENT OF BRANCH PULMONARY ARTERY STENOSIS: BALLOON ANGIOPLASTY OR ENDOVASCULAR STENTING
Authors: Chau Adolphus KT , Leung Maurice P. 
Published: June 2007

SUMMARY1. The surgical outcome of congenital heart diseases may be adversely affected by residual branch pulmonary artery stenosis, which is difficult to treat surgically.2. The objective of the present study was to evaluate the effectiveness, safety and follow‐up results of two transcatheter procedures, balloon angioplasty and endovascular stenting, for treatment of branch pulmonary arter. stenosis.3. From December 1988 to March 1997, 22 children (group 1) underwent 30 balloon angioplasties and 12 children (group 2) underwent 14 endovascular stent implantations. The overall success rates for groups 1 and 2 were 67 (20/30) and 93% (13/14), respectively, with significant increases in vessel diameter (P < 0.001, t‐test, 29d.f.; P= 0.0001, Mest, 12d.f., respectively) and decreases in pressure gradient (P < 0.0001, Mest, 29d.f.; P= 0.001; t‐test, 12 d.f., respectively). One death (3.3%) in group 1 was due to post‐dilation reactive pulmonary hypertension. No mortality occurred in group 2 children, but two migrated stents required re‐implantation of another stent. Mean follow‐up periods were 28.2 and 26.3 months for groups 1 and 2, respectively. For group 1, no significant change in vessel diameter or pressure gradient was noted on recatheterization in 12 patients. Restenosis occurred in four of 16 (25%) initial successes. Balloon redilation in four vessels were all successful. For group 2 children, although vessel diameter remained unchanged, a significant increase in pressure gradient (P= 0.02; t‐test, 11 d.f.) was noted on recatheterization. Balloon dilations on two narrowed stents caused by intimal proliferation showed only partial improvements.4. In conclusion, both balloon angioplasty and endovascular stent implantation are effective and safe, with satisfactory intermediate‐term results, for the treatment of branch pulmonary artery stenosis. Balloon angioplasty is the choice for initial treatment, whereas stent implantation, the long‐term outcome of which remains to be determined, should be reserved for older children after repeated failures with balloon dilation.
REDUCED INHIBITORY ACTIONS OF ADENOSINE A1 AND K1‐OPIOID RECEPTOR AGONISTS ON β‐ADRENOCEPTORS IN SPONTANEOUSLY HYPERTENSIVE RAT HEART
Authors: Yu X‐C , Wang H‐X , Wong TM 
Published: June 2007

SUMMARY1. The modulatory actions of both adenosine A1 and K1‐opioid receptor agonists on β‐adrenoceptor stimulation in the heart of both spontaneously hypertensive rats (SHR) and nor‐motensive Wistar‐Kyoto (WKY) rats were compared.2. In both types of rats, bot. R(‐)‐N6‐(2‐phenyliso‐propyl)adenosine (R‐PIA), an adenosine A1 receptor agonist, and U50 488H, a K1‐opioid receptor agonist, inhibited the stimulatory effects of β‐adrenoceptor activation on electrically induced [Ca2+]i transients measured by a spectrofluorometric method with fura‐2/AM as the calcium indicator. The effects of these two agonists were blocked by their respective antagonists, namely 8‐cyclopentyl‐l,3‐diprolxanthine and norbinaltorphimine.3. The inhibitory actions of both R‐PIA and U50488H on β‐adrenoceptor augmentation of electrically induce. [Ca2+]i transients in the heart were more significantly reduced in SHR than in WKY rats, suggesting the negative modulatory actions of endogenous substances on 3‐adrenoceptors were impaired in SHR, which may contribute to hypertension.
NEW INSIGHTS INTO THE TREATMENT OF HYPERTENSION
Authors: Tomlinson Brian 
Published: June 2007

SUMMARY1. The choice of initial pharmacological therapy is one area where the different hypertension management guidelines vary in recommending either the use of diuretics and beta‐blockers as preferred drugs or choosing from any of the five major classes of antihypertensives.2. Improvement in cardiovascular morbidity and mortality may have been shown most conclusively with diuretics and beta‐blockers, but the effects on coronary events with these drugs were less than predicted and the other agents have a number of theoretica. advantages.3. Recent worries regarding the possible adverse effects of calcium antagonists have led to a reappraisal of the risks and benefits of these drugs and antihypertensives i. general.4. Many patients, particularly the elderly, have other conditions that influence the choice of first‐line therapy and ethnic variations in the effects of hypertension or the efficacy or side effects of drugs should also be taken int. account.5. There is considerable heterogeneity within the major categories of antihypertensive drugs, so it is important to distinguish the different subgroups, dosages and formulations that may b. used.