bluuebunny/crossref_metadata_2025_split huggingface dataset:
GENDER‐RELATED DIFFERENCES IN THE DEVELOPMENT OF ATHEROSCLEROSIS: STUDIES AT THE CELLULAR LEVEL
Authors: Fitzpatrick Lorraine A. 
Published: June 2007

SUMMARY1. Calcified arteriosclerotic lesions have been recognized early in life as abnormalities in coronary arteries.2. We examined coronary arterial plaques as an undecalcified tissue and revealed widespread mineralization within the plaque. Non‐collagenous proteins that regulate calcification, such as osteopontin, have been identified within the atherosclerotic plaque. In vitro, smooth muscle cells derived from porcine coronary arteries express non‐collagenous proteins and type I collagen.3. We have demonstrated that oestrogen regulates the proliferation of smooth muscle cells obtained from the coronary arteries of sexually mature pigs. The inhibition of proliferation by β‐estradiol occurred in coronary smooth muscle cells (VSMC) obtained from female animals and no proliferation was noted in VSMC isolated from intact male animals after exposure to β‐estradiol.4. The dynamic changes in matrix composition and cellular proliferation in atherosclerotic vessels may be responsible for the calcification associated with the atherosclerotic plaque.
ENHANCED TISSUE POLYAMINE CONTENT IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Ibrahim Jamila , Hughes Alun D , Schachter Michael , Sever Peter S 
Published: June 2007

SUMMARY1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovascular tissues of spontaneously hypertensive rats (SHR) relative to Wistar‐Kyoto (WKY) rats. We also determined the chronic effect of 2% difluoromethylornithine (DFMO; a polyamine biosynthesis inhibitor) on tissue polyamines and hypertension.2. SHR and WKY rats were treated with either 2% DFMO or drug‐free drinking water; blood pressure was measured on alternate days and tissue polyamines were analysed at the end of the study.3. We found that spermidine and spermine concentrations were markedly raised in the ventricles, resistance vessels and liver of the SHR, in comparison with corresponding tissues of WKY rats. DFMO did not affect SHR resistance vessel and liver polyamines, although spermidine in the ventricles was reduced. The blood pressure of neither SHR nor WKY rats was affected by DFMO.4. In conclusion, this study shows for the first time a raised concentration of polyamines in the resistance vasculature of the SHR, in relation to their normotensive counterparts. The inability of DFMO to significantly reduce tissue polyamines in this study is in contrast to the effectiveness of 2% DFMO in other hypertension models, suggesting that polyamine homeostasis in this model may be stringently regulated.
ANGIOTENSIN II ACTIVATES PRESSOR AND DEPRESSOR SITES OF THE PONTOMEDULLA THAT REACT TO GLUTAMATE
Authors: Chai CY , Chen SY , Lin AMY , Tseng CJ 
Published: June 2007

SUMMARY1. In cats anaesthetized with a mixture of α‐chloralose (40 mg/kg) and urethane (400 mg/kg) and in rats anaesthetized with a mixture of α‐chloralose (60 mg/kg) and urethane (800 mg/kg), changes in systemic arterial pressure (SAP), heart rate (HR) and sympathetic activities of vertebral (VNA) and renal (RNA) nerves were determined following the micro‐injection of angiotensin II (AngII; 0.16 mmol/L; 50 nL) into the pressor and depressor sites of the pontomedulla previously reacted to a microinjection of monosodium l‐glutamate (Glu; O.1 mol/L; 50 nL). Pressor sites included gigantocellular tegmental field (FTG) and dorsal medulla (DM) and rostral ventrolateral medulla (VLM). The depressor site was the caudal VLM (CVLM). The effects of losartan (1 mmol/L; 50 nL), a specific AT1 receptor non‐peptide antagonist for AngII, on responses induced by AngII in the VLM, DM and CVLM were also determined.2. In 30% of pressor sites in the FTG, 55% in the VLM and 67% in the DM and in 76% of depressor sites in the CVLM previously exposed to Glu, microinjection of AngII to the same site produced pressor or depressor responses similar to that of Glu, but smaller in magnitude, particularly in the pressor VLM. Changes in both VNA and RNA induced by AngII were also smaller than those induced by Glu, particularly RNA from DM activation.3. In the dorsal motor nucleus of the vagus, AngII, as Glu, produced marked bradycardia, but again this was smaller in magnitude than the bradycardia produced by Glu.4. In rats, in the DM near or around the nucleus of the solitary tract where Glu increased SAP, microinjection of AngII (0.8 mmol/L; 60 nL) produced a depressor response, while the microinjection of 1.6 mmol/L (60 nL) AngII produced a pressor response.5. Losartan blocked the increases in SAP induced by AngII in the VLM and DM. Decreases in SAP induced by AngII in the CVLM, however, were only slightly decreased by losartan.6. Our data suggest that a significant portion of pressor and depressor sites of the pontomedulla contain neurons responsive to both AngII and Glu. In neurons in the VLM and DM, AngII produced pressor responses that were primarily mediated through AT1 receptors, while the depressor actions of AngII in the CVLM were not mediated by AT1 receptors.
A STUDY OF ANGIOTENSIN II RECEPTORS AFTER CHRONIC INHIBITION OF NITRIC OXIDE SYNTHASE IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Yang Y. , Macdonald GJ , Duggan KA 
Published: June 2007

SUMMARY1. Nitric oxide (NO) synthase inhibition, induces a sustained increase in blood pressure and amplifies the pressor response to infused angiotensin II (AngII). This study was designed to investigate the contribution of AngII receptors to the elevated blood pressure and enhanced pressor response to AngII in the spontaneously hypertensive rat (SHR) chronically treated with NG‐nitro‐l‐arginine‐methyl ester (l‐NAME).2. Two groups of 13 week old female SHR were housed four to a box. Group I rats received l‐NAME for 7 days (2.5 mg/kg per day) in their drinking water. Group II rats received water only. Blood pressure was monitored daily by tail‐cuff plethysmography. Plasma AngII was measured by radioimmunoassay. Aortic and uterine receptor binding was determined by saturation analysis using [125I]‐Sar8, Ile1)AngII. Data was analysed using the computer program ligand.3. Mean systolic blood pressure was significantly elevated in rats treated with l‐NAME compared with the control group. Plasma AngII concentration was slightly decreased in rats treated with l‐NAME compared with control. Densities of both aortic and uterine AngII receptors increased significantly following NO synthase inhibition. Receptor affinity in the aorta decreased in the l‐NAME group compared with control. However, uterine AngII receptor affinity was unchanged.4. We conclude that the increased blood pressure and enhanced pressor responsiveness that occurs with chronic inhibition of NO synthesis may result partly from increased vascular AngII receptor expression.
BRAIN ANGIOTENSIN AND CIRCULATORY CONTROL
Authors: Muratani Hiromi , Teruya Hiroshi , Sesoko Shogo , Takishita Shuichi , Fukiyama Koshiro 
Published: June 2007

SUMMARY1. Components of the renin‐angiotensin system (RAS) are found in the brain; both outside and inside the blood‐brain barrier.2. Almost all of the classical actions of the brain RAS are attributable to angiotensin (Ang) II and mediated by AT1 receptors.3. Circumventricular organs (CVO), which lack the blood‐brain barrier, are rich in AngII receptors and monitor circulating AngII levels. In vivo binding studies suggest that the CVO are also accessible to cerebrospinal fluid‐derived AngII.4. The median preoptic nucleus, paraventricular hypothalamic nucleus, supraoptic nucleus, nucleus tractus solitarius and ventrolateral medulla are inside the blood‐brain barrier and are sites of action of brain AngII. In these nuclei, AngII seems to act as an excitatory neurotransmitter or neuromodulator.5. Actions of AngII in the brain, both inside and outside the blood‐brain barrier, are implicated in the central regulation of blood pressure and sympathetic outflow, release of hypothalamic and pituitary hormones and renal sodium handling.6. Alterations in the activity of brain AngII may be involved in the mechanisms of some types of hypertension.
IBUDILAST PROTECTS AGAINST NEURONAL DAMAGE INDUCED BY GLUTAMATE IN CULTURED HIPPOCAMPAL NEURONS
Authors: Tominaga Yasuhiro , Nakamura Yoichi , Tsuji Koji , Shibata Taiho , Kataoka Kiyoshi 
Published: June 2007

SUMMARY1. The effect of ibudilast, a drug that has been clinically used for asthma and the improvement of cerebrovascular disorders, was examined on glutamate neurotoxicity in cultured neurons from rat hippocampus.2. The extent of neuronal damage induced by exposure of the neurons to glutamate for 5 min was estimated by the activity of lactate dehydrogenase (LDH) released from degenerated neurons into the medium during a 24 h postexposure period. When ibudilast was added into all pre‐incubation, exposure and postexposure media, the extent of neuronal damage decreased to approximately half that of control at an ibudilast concentration of 43 μmol/L.3. The neuroprotective effects of ibudilast were dose‐dependent. Sufficient protection was detected even when ibudilast was added only into the postexposure medium.4. The extent of 45Ca2+ influx during glutamate exposure was slightly reduced by the addition of ibudilast. Intracellular cAMP, as measured by radioimmunoassay, was increased by neuronal exposure to glutamate and then decreased after the removal of glutamate; however in the presence of ibudilast, AMP was maintained at the high level.5. These results suggest that protection against glutamate neurotoxicity by ibudilast is not only attributable to the inhibition of phenomena that occur during glutamate exposure, such as Ca2+ influx, but also to some beneficial metabolic changes that are induced by a sustained high level of intracellular cAMP.
EXAMINATION OF THE ROLE OF NITRIC OXIDE SYNTHASE AND RENAL KALLIKREIN AS CANDIDATE GENES FOR ESSENTIAL HYPERTENSION
Authors: Friend LR , Morris BJ , Gaffney PT , Griffiths LR 
Published: June 2007

SUMMARY1. Nitric oxide synthase and renal kallikrein are both involved in blood pressure regulation. Genes for these enzymes may, therefore, be considered candidates for hypertension pathogenesis.2. In the present study, genotypes for nitric oxide synthase and renal kallikrein microsatellite markers were determined in a cross‐sectional association analysis of hypertensive patients and normotensive control subjects.3. Results from this study did not indicate an association of either of the candidate gene polymorphisms with essential hypertension. Hence, findings for this study do not support a role for these genes in human hypertension.
NO DIFFERENCE IN THE PROPORTION OF INSULIN RECEPTOR EXON 11 +/‐ ISOFORM mRNA IN THE LIVER OF RATS AFTER DEVELOPMENT OF HYPERTENSION
Authors: Lou Yi‐kun , Zee Robert YL , Li Ming , Morris Brian J 
Published: June 2007

SUMMARY1. There are two functionally different isoforms of the insulin receptor in humans and rats. We hypothesized that a change in their relative proportion could be of relevance to insulin resistance in hypertension.2. A reverse‐transcriptase polymerase chain reaction technique was established for the detection of mRNA for the exon 11+ and exon 11—isoforms and the proportion of each was determined in 3, 6, 9 and 12 week old spontaneously hypertensive rats and Wistar‐Kyoto rats, as well as adrenocorticotrophin (ACTH)‐induced hypertensive rats and controls.3. The proportion of the exon 11+ form (∼95%) and exon 11—form (∼5%) was similar in the liver of all rats studied.4. We conclude that there is no change in insulin receptor isoform expression in the liver in the models of hypertension studied.
FULL EXPRESSION OF THE EXAGGERATED SALT APPETITE OF THE SPONTANEOUSLY HYPERTENSIVE RAT REQUIRES A PRENATAL FACTOR
Authors: Erkadius E. , Morgan TO , Di Nicolantonio R. 
Published: June 2007

SUMMARY1. The spontaneously hypertensive rat (SHR) exhibits a lower bodyweight in utero and an exaggerated salt appetite post partum. To determine whether salt appetite is affected by the perinatal environment, we measured the salt appetite of embryo‐cross‐transferred SHR and Wistar Kyoto (WKY) rats at maturity.2. One‐cell embryos were collected from the oviducts of donor rats and transferred into the oviducts of recipients through the infundibulum. The salt appetite of the resultant female offspring for 0.10 and 0.15mol/L saline was measured at 20–30 weeks of age.3. Salt intake of SHR gestated in WKY rats was significantly lower than that of SHR gestated in SHR, while that of WKY rats gestated in SHR was higher than that of WKY rats gestated in WKY rats.4. Therefore, some maternal factor plays a role in the development of the exaggerated salt appetite of the SHR. This factor is also able to affect the later salt appetite of WKY rat offspring born to SHR surrogates.
Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: MOLECULAR MECHANISMS OF ANGIOTENSIN II (AT1a) RECEPTOR ENDOCYTOSIS
Authors: Thomas Walter G , Thekkumkara Thomas J , Baker Kenneth M 
Published: June 2007

SUMMARY

Angiotensin II (AngII) initiates a variety of cellular responses through activation of type 1 (AT1; with subtypes AT1a and AT1b) and type 2 (AT2) cell surface angiotensin receptors. Both AT1 and AT2 receptors couple to heterotrimeric guanyl nucleotide binding proteins (G‐proteins) and generate intracellular signals following recognition of extracellular AngII, but only AT1 is targeted for the rapid ligand‐stimulated endocytosis (internalization) typical of many plasma membrane receptors.
AT1 endocytosis proceeds through clathrin‐coated pits and is independent of G‐protein coupling which predicts that the AngII‐AT1 receptor complex attains a conformation necessary for interaction with the endocytotic machinery, but separate from receptor signalling activation.
The function of AT1 endocytosis and the reason for the disparity between AT1 and AT2 endocytosis is not fully appreciated, but the latter probably reflects differences in the primary amino acid sequence of these two receptor types.
For many receptors that undergo internalization, it has been established that internalization motifs (2–6 amino acids, often incorporating crucial tyrosine and hydrophobic amino acids) within the cytoplasmic regions of the receptor mediate the selective recruitment of activated receptors into clathrin‐coated pits and vesicles.
Mutagenesis studies on the AT1a receptor, aimed at identifying such motifs, reveal that sites within the third cytoplasmic loop and the cytoplasmic carboxyl terminal region are important for AngII‐stimulated AT1a receptor endocytosis.
AT1 RECEPTOR ANTAGONIST, TCV 116, DOES NOT PREVENT CARDIAC HYPERTROPHY IN SALT‐LOADED DAHL SALT‐SENSITIVE RATS
Authors: Sugimoto Koh‐ichi , Gotoh Eiji , Takasaki Izumi , Ebina Toshiaki , Iwamoto Tamio , Takizawa Toshikazu , Shionoiri Hiroshi , Ishii Masao 
Published: June 2007

SUMMARY1. We investigated the effects of direct blockade of angiotensin II (AngII) by a potent, non‐peptide angiotensin II type 1 (AT1) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt‐loaded Dahl salt‐sensitive rats.2. Six week old male Dahl salt‐sensitive rats (n= 44) were fed a 4% salt diet and were simultaneously given various doses of TCV 116 orally for 7 weeks. Each control group received vehicle alone.3. Dietary high salt intake elevated blood pressure continuously and caused left ventricular hypertrophy in rats treated with vehicle. TCV 116 had a minor effect on the rise in blood pressure. Left ventricular mass (left ventricular weight/body‐weight) decreased slightly but not significantly, in rats treated with 3mg/kg per day of TCV 116 (n= 8). Higher doses of TCV 116 (6 and 10 mg/kg per day; n= 8 each) did not show a decrease in left ventricular mass compared with the vehicle control.4. These results suggest that AngII blockade has only minor effects on hypertension and on cardiac hypertrophy in salt‐loaded Dahl salt‐sensitive rats and that the renin‐angiotensin system may not contribute to the development of cardiac hypertrophy in Dahl salt‐sensitive rats on a moderately high‐salt diet.
DISTRIBUTION AND ANTI‐INFLAMMATORY EFFECT OF MESALAZINE ON CARRAGEENAN‐INDUCED COLITIS IN THE RABBIT
Authors: Kitano A. , Matsumoto T. , Oshitani N. , Nakagawa M. , Yasuda K. , Watanabe Y. , Tomobuchi M. , Obayashi M. , Tabata A. , Fukushima R. , Okabe H. , Nakamura S. , Obata A. , Okawa K. , Kobayashi K. 
Published: June 2007

SUMMARY1. A controlled‐release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease.2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan‐induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives.3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5‐aminosalicylic acid and acetyl‐5‐aminosalicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine.4. The present study indicates that slow release 5‐aminosalicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan‐induced colitis in the rabbit.
SYMPOSIUM Experimental Biology 1995 Endothelin Receptors: Role in Renal Function and Dysfunction ENDOTHELINS: RENAL TUBULE SYNTHESIS AND ACTIONS
Authors: Kohan Donald E 
Published: June 2007

SUMMARY1. Renal tubules and, in particular, the inner medullary collecting duct, produce endothelin and express cognate receptors.2. Endothelins inhibit vasopressin‐stimulated cAMP accumulation and water reabsorption in the collecting duct; endothelins may also inhibit sodium reabsorption in the proximal tubule and collecting duct.3. Autocrine inhibition of sodium and water reabsorption in the inner medullary collecting duct by endothelin may play a role in maintaining extracellular fluid volume homeostasis.4. Derangements in autocrine inhibition of sodium and water reabsorption in the inner medullary collecting duct by endothelin may be involved in the pathogenesis of the hypertensive state.5. Nephron‐derived endothelins may function in a paracrine manner to regulate interstitial, juxtaglomerular and vascular smooth muscle cell function.
EFFECTS OF ENDURANCE TRAINING ON SUPEROXIDE DISMUTASE ACTIVITY, CONTENT AND mRNA EXPRESSION IN RAT MUSCLE#
Authors: Oh‐ishi S. , Kizaki T. , Nagasawa J. , Izawa T. , Komabayashi T. , Nagata N. , Suzuki K. , Taniguchi N. , Ohno H. 
Published: June 2007

SUMMARY1. The purpose of the present study was to investigate the changes in superoxide dismutase (SOD) isoenzyme (Mn2+‐SOD and Cu2+, Zn2+‐SOD) activities, contents and mRNA expressions in rat skeletal muscle during endurance training and a single bout of exercise.2. Thirty‐eight male Wistar rats were divided into untrained (U) and trained (T) groups. The T group rats were treadmill‐trained for 9 weeks. The activity, content and mRNA expression of Mn2+‐SOD and Cu2+, Zn2+‐SOD were determined in the soleus muscle of each rat.3. Mn2+‐SOD activity and content in the T group were significantly higher than in the U group, both at rest (22 and 21%, respectively) and after exercise (24 and 46%, respectively), while a single bout of exercise affected neither the activity nor content of Mn2+‐SOD in either group.4. The content of Cu2+, Zn2+‐SOD in both groups was not different at rest and after exercise, although its activity at rest was significantly higher in the T group than in the U group (by 29%).5. After exercise, the expression of Mn2+‐SOD mRNA was markedly attenuated only in the U group (49%); the expression of Cu2+, Zn2+‐SOD mRNA was not influenced by exercise.6. Our results suggest that adequate endurance training increases both the activity and content of Mn2+‐SOD and that untrained rats are rather susceptible to oxidative stress during physical exercise. It thus appears that Mn2+‐SOD provides a reliable index of physical training.7. The results obtained in the present study also suggest that muscle has the capacity of responding to training in such a manner as to reduce the potential harm arising from the accumulation of oxygen free radicals resulting from enhanced metabolic activity.
ACUTE EFFECTS OF ORAL GLIBENCLAMIDE ON BLOOD PRESSURE AND FOREARM VASCULAR RESISTANCE IN DIABETICS
Authors: Sundaresan Purnima , Lykos Denise , Daher AH , Morris Richard , Diamond Terence , Howes Laurence G. 
Published: June 2007

SUMMARY1. To determine the effects of an acute oral dose of glibencla‐mide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+ATP channel activating vasodilator diazoxide, a placebo‐controlled, double‐blind cross‐over study was performed in eight male volunteers with non‐insulin‐dependent diabetes mellitus.2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75–30 mg/kg per min) and noradrenaline (25–100 ng/kg per min) were measured by venous occlusion plethysmography.3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01).4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra‐arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+ATP channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.