bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANTI‐OBESITY AND ANTI‐DIABETIC EFFECTS OF MAZINDOL IN YELLOW KK MICE: ITS ACTIVATING EFFECT ON BROWN ADIPOSE TISSUE THERMOGENESIS
Authors: Yoshida Toshihide , Umekawa Tsunekazu , Wakabayashi Yasuo , Yoshimoto Kanji , Sakane Naoki , Kondo Motoharu 
Published: June 2007

SUMMARY1. The anti‐obesity and anti‐diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57B1 control mice.2. The study compound was fed through a gastric tube at a rate of 1 or 2 mg/kg per day (0.01 mol/L HC1 as control) for 2 weeks. The following parameters were compared in treated and control animals: bodyweight, food intake, white adipose tissue (WAT) weight, brown adipose tissue (BAT) weight and its thermogenesis, noradrenaline (NA) turnover, blood glucose and serum insulin levels and glucose transporter 4 (GLUT4).3. Furthermore, bodyweight loss of mice pair‐fed the same amount of food as the mazindol‐treated mice for 2 weeks was measured.4. Mazindol significantly decreased food intake and significantly increased guanosine‐5′‐diphosphate‐binding in BAT mitochondria and NA turnover in BAT in both yellow KK and C57B1 groups. The amounts of WAT in subcutaneous, mesenteric and retroperitoneal regions and bodyweights were significantly decreased in both groups. Bodyweight loss in mice pair fed with the mazindol‐treated groups was approximately 70% compared with that in the mazindol‐treated groups. Furthermore, mazindol decreased the levels of blood glucose and serum insulin during the glucose overloading test in yellow KK mice, but it did not influence the GLUT4 protein concentration in WAT and muscle.5. These observations suggest that mazindol possesses both an anti‐obesity action, due to the inhibition of appetite as well as the activation of BAT thermogenesis via increased NA turnover in BAT, and an anti‐diabetic action. Consequently, mazindol may be useful for the treatment of obesity as well as non‐insulin‐dependent diabetes mellitus in obese persons.
COMPARATIVE RELAXANT EFFECTS OF CROMAKALIM AND PINACIDIL ON THE TONIC CONTRACTION OF CANINE CORONARY ARTERY INDUCED BY PHORBOL 12,13‐DIBUTYLATE
Authors: Kuromaru O. , Sakai K. 
Published: June 2007

SUMMARY1. Phorbol esters, activators of protein kinase C (PKC), have been widely used to investigate the role of PKC in the regulation of smooth muscle contraction. However, limited studies have so far been made of the sensitivity of the contraction induced by phorbol esters to relaxant drugs. We therefore examined the relaxant effects of the K+ channel openers, cromakalim and pinacidil, on the tonic contraction of canine isolated coronary artery rings induced by phorbol 12,13‐dibutylate (PDBu).2. In rings contracted with 10−7mol/L PDBu, cromakalim and pinacidil, as well as nifedipine, produced a concentration‐dependent relaxation. At their maximum effects, both cromakalim and nifedipine caused a partial relaxation, whereas pinacidil produced nearly a full relaxation.3. The relaxant effects of cromakalim and pinacidil were effectively antagonized by the ATP‐sensitive K+ channel blocker, glibenclamide (10−6mol/L).4. In the presence of nifedipine, high K+ was ineffective while PDBu (10−7mol/L) still induced a tonic contraction. This PDBu‐induced contraction was inhibited by concentrations of cromakalim and pinacidil higher than those needed in the absence of nifedipine.5. In rings partially depolarized with 35mmol/L KCl, the ability of cromakalim to inhibit PDBu‐induced contractions in the presence of nifedipine was completely abolished. Under the same conditions, the relaxant response to pinacidil, unlike cromakalim, was inhibited only partially.6. These results suggest that cromakalim inhibits PDBu‐induced contractions through an opening of K+ channels. Pinacidil does so by a mechanism shared with cromakalim as well as by another that is independent of this K+ channel opening action. These multiple modes of action may confer on pinacidil a vasorelaxant activity greater than that of cromakalim.
DIETARY FISH OIL PREVENTS THE DEVELOPMENT OF RENAL DAMAGE IN SALT‐LOADED STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Hobbs Leanne M , Rayner Timothy E , Howe Peter RC 
Published: June 2007

SUMMARY1. Stroke‐prone spontaneously hypertensive rats (SHRSP) fed a high salt diet rapidly develop proteinuria, a marker of renal damage. We have recently shown that supplementing the diet of these rats with pure omega‐3 fatty acids can inhibit the development of proteinuria. The aim of the present study was to examine the underlying renal pathology and to see whether a similar benefit could be obtained with fish oil or canola oil.2. Diets containing sodium (2% by weight) and 5% fish oil, canola oil, olive oil or safflower oil (the latter two serving as controls) were fed to groups of eight young SHRSP and the development of hypertension and proteinuria was monitored. After 9 weeks, rats were killed and their kidneys were taken for histological examination and fatty acid analysis. Urinary protein was characterized electrophoretically.3. Patterns of protein excretion were consistent with the appearance of pathological changes in both glomeruli and tubules. Fish oil inhibited the elevation of blood pressure, prevented the development of proteinuria and minimized histological lesions. However, in rats fed canola oil, hypertension and renal damage were equally severe as in rats fed olive or safflower oil.4. The prevention of hypertensive renal damage by dietary fish oil may be attributable to increased incorporation of longchain omega‐3 fatty acids in the kidney.
EFFECT OF COFFEE AND TEA DRINKING ON POSTPRANDIAL HYPOTENSION IN OLDER MEN AND WOMEN
Authors: Rakic V. , Beilin LJ , Burke V. 
Published: June 2007

SUMMARY1. A postprandial fall in blood pressure (BP) in older men and women increases the risks of falls and impaired cerebral perfusion. Postprandial hypotension has been suggested to be greater in hypertensive subjects, particularly in those on antihypertensive medication.2. Caffeine, given as tablets or as strong coffee, may attenuate postprandial falls in BP in older subjects, but findings are not consistent.3. In a randomized controlled intervention in 171 healthy non‐smokers over the age of 50 years, we compared the effects of coffee‐drinking with abstaining from caffeine in normotensives (NT), untreated hypertensives (UNHT) and subjects on drug treatment for hypertension (TRHT). Tea drinking was a third intervention used only in TRHT.4. After adjustment for the effects of the initial value on changes in BP, there were no significant differences related to hypertension or to antihypertensive agents in the magnitude of postprandial falls in BP.5. After the intervention, changes in fasting supine and standing systolic BP and heart rate (HR) were not significantly different from controls in NT, UNHT and TRHT, but fasting supine and standing diastolic BP were significantly higher in coffee drinkers in the UNHT group.6. In normotensive coffee drinkers there was a significant reduction in the postprandial fall in supine systolic BP of 4.1 mmHg (± s.e.m. 1.1) and in standing systolic BP of 5.2 ± 1.6 mmHg. Among untreated hypertensives, abstainers showed a significant attenuation of the postprandial fall in supine, but not standing, systolic BP. Among treated hypertensives who were tea drinkers the postprandial fall decreased for supine systolic BP by 3.8 ± 1.2 mmHg (P= 0.029) and for standing systolic BP by 5.2 ± 2.1 mmHg.7. Both tea and coffee were potentially beneficial in decreasing postprandial falls in systolic BP, but coffee drinking may increase fasting diastolic pressures in untreated hypertensives.
VALIDATION OF AN ECHOCARDIOGRAPHIC ASSESSMENT OF CARDIAC FUNCTION FOLLOWING MODERATE SIZE MYOCARDIAL INFARCTION IN THE RAT
Authors: Burrell Louise M , Chan Robert , Phillips Paddy A , Calafiore Paul , Tonkin Andrew M , Johnston Colin I 
Published: June 2007

SUMMARY1. The present study determined whether two dimensional guided M‐mode echocardiography could assess left ventricular (LV) geometry and function following a moderate size myocardial infarction in the rat.2. Myocardial infarction (MI) was induced by left coronary artery ligation and rats were studied 4 weeks later. Infarct rats showed increased LV internal diastolic diameter (7.33 ± 0.8 vs 5.91 ± 0.6 mm; P > 0.001), LV systolic diameter (3.73 ± 1.2 vs 1.87 ± 0.6 mm; P > 0.001) and thickening of the noninfarcted posterior wall compared with sham operated rats (1.81 ± 0.2 vs 1.47 ± 0.3; P > 0.001; n= 10/group; mean ± s.d.). Systolic function was impaired in infarct rats who showed reduced fractional shortening (50 ± 12 vs 68 ± 9%; P > 0.001) and fractional area change (41 ± 14 vs 78 ± 5%; P > 0.001). Infarct size measured echocardiographically was comparable to that measured by quantitative histological examination (29 ± 10 vs 28 ± 5%; NS).3. The present study indicates that postinfarction remodelling leading to LV cavity dilation, hypertrophy of surviving myocardium and impaired systolic function is apparent 4 weeks following moderate size MI in the rat.4. Transthoracic echocardiography is a noninvasive technique that may be used to assess serially the efficacy of therapeutic interventions designed to prevent remodelling in moderate size MI in the rat.
REGULATION BY PROTEIN KINASE C OF TRANSFORMING GROWTH FACTOR‐β1 ACTION ON THE PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Saltis John , Bobik Alex 
Published: June 2007

SUMMARY1. This study examined the role of protein kinase C (PKC) on the action of transforming growth factor‐β1 (TGF‐β1) to regulate the proliferation of vascular smooth muscle cells (VSMC) isolated from the aorta of the spontaneously hypertensive rat (SHR).2. Down‐regulation of PKC by prolonged exposure to phorbol 12‐myristate 13‐acetate (PMA) completely inhibited the ability of TGF‐β1 to potentiate epidermal growth factor‐stimulated proliferation of VSMC.3. In contrast, the inhibitory effect of TGF‐β1 on serumstimulated proliferation of VSMC was not altered by PMA action.4. These results suggest that PKC‐dependent signalling pathways involved in the regulation of growth by TGF‐β1 may be important in any proliferative component of vascular hypertrophy that develops in the SHR.
NEW DIAGNOSTIC TESTS FOR CUSHING'S SYNDROME: USES OF NALOXONE, VASOPRESSIN AND ALPRAZOLAM
Authors: Jackson RV , Hockings GI , Torpy DJ , Grice JE , Crosbie GV , Walters MM , Strakosch CR 
Published: June 2007

SUMMARY1. We set out to investigate whether the administration of naloxone alone, naloxone plus vasopressin (AVP) or naloxone plus alprazolam to patients with Cushing's syndrome would result in a blunted dynamic response of the pituitary‐adrenal axis compared with normal volunteers. Cushing's syndrome is often difficult to diagnose. It would be helpful if new tests were available to help in the biochemical distinction between Cushing's syndrome and non‐Cushing's syndrome patients.2. Naloxone testing correctly distinguished all seven patients with Cushing's syndrome (four pituitary Cushing's, two adrenal adenomas, one ectopic ACTH) from normal. Six patients were distinguished by the per cent change of plasma ACTH from basal being less than the normal range of 10 volunteers. The seventh patient (a pituitary Cushing's) was distinguished by the per cent change from basal of plasma cortisol being less than the normal range.3. Naloxone plus AVP testing of two of four patients with pituitary Cushing's showed a smaller per cent change for both ACTH and cortisol compared with five normal volunteers, correctly distinguishing Cushing's from the normals.4. Naloxone plus alprazolam did not distinguish Cushing's from normal.5. Naloxone testing and naloxone plus AVP testing appear to be promising methods of distinguishing Cushing's syndrome from normal. Further experience with these tests, especially with obese and pseudo‐Cushing's individuals, will be necessary to determine their place in the diagnosis and differential diagnosis of the cause of Cushing's syndrome.
DIFFERENT ALLELIC PATTERNS AT CHROMOSOME 11q13 IN PAIRED ALDOSTERONE‐PRODUCING TUMOURS AND BLOOD DNA
Authors: Gordon Richard , Gartside Michael , Tunny Terry , Stowasser Michael 
Published: June 2007

SUMMARY1. We previously reported loss of heterozygosity (LOH) at region q13 of chromosome 11 in five aldosterone‐producing tumours (APT) using restriction fragment length polymorphism (RFLP) analysis, including two from patients with familial hyperaldosteronism.2. In the present study, microsatellite markers were used to examine 33 informative paired blood and tumour DNA samples from patients with APT for LOH at three loci that map to chromosome 11q13.3. LOH at one or more loci was detected in seven (21.2%) tumour DNA samples.4. This study provides further support that mutations at 11q13 may be involved in the underlying pathophysiology of aldosterone‐producing tumours of the adrenal cortex.
CARDIAC GROWTH DURING HIGH AND LOW DOSE PERINDOPRIL TREATMENT IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Black MJ , Bertram JF , Johnston CI 
Published: June 2007

SUMMARY1. The effect of high and low dose angiotensin converting enzyme (ACE) inhibition and the contribution of bradykinin potentiation in this treatment on left and right ventricle weights and wall volume was investigated in immature spontaneously hypertensive rats (SHR).2. Male SHR were treated from 7 to 11 weeks of age with perindopril (an ACE inhibitor) at a low dose of 0.1 mg/kg per day or a high dose of 1 mg/kg per day. Half the animals were also treated with a bradykinin receptor antagonist, HOE 140 (500 μg/kg per day).3. After 4 weeks of treatment, hearts were arrested in diastole and perfusion fixed. The right and left ventricle plus septum were weighed, cut into 1 mm slices and volume was determined using the Cavalieri principle.4. Low dose perindopril treatment did not significantly affect blood pressure in the SHR. High dose perindopril treatment maintained blood pressure at a level similar to Wistar‐Kyoto (WKY) rats.5. Growth of the right ventricle was not influenced by ACE inhibition. However, high dose treatment significantly lowered the left ventricle plus septum volume: bodyweight ratio (LV + S VOL:BWT) compared with control SHR (2.85 ± 0.02 vs 3.36 ± 0.08 mm3/g, respectively) to a level similar to the normotensive WKY rats (2.80 ± 0.11 mm3/g). Similarly, low dose treatment significantly lowered the LV + S VOL:BWT ratio (2.89 ± 0.09 mm3/g). HOE 140 treatment did not reverse the effect of ACE inhibition. Similar effects were observed on left ventricular weights.6. ACE inhibition, independent of its blood pressure lowering effect, prevents the development of left ventricular hypertrophy in the SHR but does not influence growth of the right ventricle. This effect of ACE inhibition does not appear to be mediated by bradykinin potentiation.
CHANGES IN ANGIOTENSIN II METABOLISM CONTRIBUTE TO THE INCREASED PRESSOR RESPONSE TO ANGIOTENSIN AFTER CHRONIC TREATMENT WITH l‐NAME IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Yang Y. , Macdonald GJ , Duggan KA 
Published: June 2007

SUMMARY1. Administration of nitric oxide (NO) synthase inhibitors, such as l‐NAME, is associated with an increase in blood pressure and an increase in pressor responsiveness to infused angiotensin II (AngII). The present study was designed to investigate the contribution of changes in the metabolism of AngII to the enhanced pressor response to AngII in the spontaneously hypertensive rat (SHR; 14 weeks old) chronically treated with l‐NAME.2. Group I rats received l‐NAME for 7 days (5 mg/kg per day) in their drinking water. Group II rats received water only. On day 7, rats were anaesthetized and metabolic clearance studies were performed. AngII concentrations in plasma and infusate were measured by radioimmunoassay.3. Urinary NO2 was unchanged after l‐NAME treatment, while NO3 decreased compared with control. Mean arterial pressure (MAP) was higher in the l‐NAME treated rats than in control. After 30min infusion of AngII, MAP increased significantly in both groups, although the increase was larger in l‐NAME‐treated than control rats. The metabolic clearance rate of AngII was significantly lower in l‐NAME‐treated rats than in the control group.4. We conclude that chronic NO synthase inhibitors, such as l‐NAME, cause a decrease in the rate at which AngII is metabolized. This decrease, in combination with the increase in the number of vascular AngII receptors, may account for the reported increase in pressor responsiveness to infused AngII.
Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: ANGIOTENSIN RECEPTORS AND DEVELOPMENT: THE KIDNEY
Authors: Alcorn Daine , McCausland Jane E , Maric Christine 
Published: June 2007

SUMMARY

This brief review examines the evidence that angiotensin II (AngII) is essential for kidney development.
Several components of the renin‐angiotensin system (RAS) are detected in the foetal kidney early in development.
Angiotensin II is essential for normal foetal and neonatal renal function.
Angiotensin II receptors transduce important signals leading to growth and development.
Angiotensin receptor subtypes show spatial and temporal specificity of localization throughout renal development.
Angiotensin converting enzyme (ACE) inhibition or AngII receptor blockade (specifically AT1 subtype blockade) results in functional and structural abnormalities of the developing kidney in both experimental and clinical situations.
While chronic postnatal RAS blockade in rats is associated with structural damage to tubules and blood vessels of the kidney, reports differ on whether treatment also affects glomerular induction and growth.
In metanephric organ culture, glomerular induction proceeds despite AngII receptor blockade.
In summary, the evidence suggests that AngII is not essential for nephron induction and glomerular development in the rat kidney. However, AngII is essential for normal growth and development of renal tubules and vasculature.
Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN
Authors: McKinley MJ , McAllen RM , Pennington GL , Smardencas A. , Weisinger RS , Oldfield BJ 
Published: June 2007

SUMMARY

Autoradiographic binding studies have shown that the AT1 receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT1 receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco‐lumbar spinal cord.
While there are differences between species, AT2 receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
Circulating AngII acts on AT1 receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
Centrally administered AngII may act on AT1 receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
Recent evidence shows that centrally administered AT1 antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT1 receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.
Proceedings of the Symposium ‘Angiotensin AT1Receptors: From Molecular Physiology to Therapeutics’: FUNCTIONS OF ANGIOTENSIN PEPTIDES IN THE ROSTRAL VENTROLATERAL MEDULLA
Authors: Dampney RAL , Hirooka Y. , Potts PD , Head GA 
Published: June 2007

SUMMARYIt was first shown several years ago that the rostral part of the ventrolateral medulla (VLM) contains a high density of receptor binding sites for angiotensin II (AngII). In the present paper we briefly review recent studies aimed at determining the actions of both exogenous and endogenous angiotensin peptides in the rostral VLM, as well as their specific sites of action.The results of these studies have shown that angiotensin peptides can excite pressor and sympathoexcitatory neurons in the rostral VLM, but do not appear to affect non‐cardiovascular neurons in this region.It is known that pressor neurons in the rostral VLM include both catecholamine and non‐catecholamine neurons. There is evidence that, at least in conscious rabbits, both of these types of neurons are activated by AngII. The specific endogenous angiotensin peptide or peptides that affect pressor neurons in the rostral VLM have not yet been definitively identified.It is also possible that different angiotensin peptides may have different effects on pressor neurons in the rostral VLM, mediated by different receptors. Further studies will be needed to define these different functions as well as the specific receptors and cellular mechanisms that subserve them.
ANTEROVENTRAL WALL OF THE THIRD VENTRICLE AND DORSAL LAMINA TERMINALIS: HEADQUARTERS FOR CONTROL OF BODY FLUID HOMEOSTASIS?
Authors: McKinley MJ , Pennington GL , Oldfield BJ 
Published: June 2007

SUMMARY1. The subfornical organ, median preoptic nucleus and the organum vasculosum of the lamina terminalis (OVLT) are a series of structures situated in the anterior wall of the third ventricle and form the lamina terminalis. The OVLT and ventral part of the median preoptic nucleus are part of a region known as the anteroventral third ventricle region.2. Data from many laboratories, using techniques ranging from lesions, electrophysiology, neuropharmacology, Fos expression, immunohistochemistry and receptor localization, indicate that the tissue in the lamina terminalis plays a major role in many aspects of body fluid and electrolyte balance.3. The subfornical organ and OVLT lack the blood‐brain barrier and detect alterations in plasma tonicity and the concentrations of circulating hormones such as angiotensin II and possibly atrial natriuretic peptide and relaxin.4. This information is then integrated within the lamina terminalis (probably in the median preoptic nucleus) with neural signals from other brain regions. The neural output from the lamina terminalis is distributed to a number of effector sites including the paraventricular (both parvo‐ and magno‐cellular parts) and supraoptic nuclei and influences vasopressin secretion, water drinking, salt intake, renin secretion, renal sodium excretion and cardiovascular regulation.