bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODULATION OF VASOCONSTRICTION BY ENDOTHELIUM‐DERIVED NITRIC OXIDE: THE INFLUENCE OF VASCULAR DISEASE
Authors: Woodman Owen L. 
Published: June 2007

SUMMARY1. The endothelium makes a significant contribution to the regulation of vascular tone through the release of potent vasodilator agents such as nitric oxide (NO) and prostacyclin (PGI2) as well as vasoconstrictor compounds such as endothelin. Recognition of this function of the endothelium has created a new focus for the investigation of vasoconstrictor activity under physiological and pathological conditions.2. It has been well established that removal of the endothelium enhances responses to a variety of contractile agents in conductance arteries and that such modulation is predominantly due to the release of NO. The use of selective inhibitors of NO synthesis has confirmed that the endothelium‐derived nitric oxide also modulates constriction in resistance vessels.3. In a number of cardiovascular disease states there is impairment of endothelial function. Thus one of the consequences of atherosclerosis, hypertension and ischaemia is a reduction in endothelium‐dependent vasodilatation, both at a basal level and in response to endogenous and exogenous stimuli. In addition, enhanced responses to vasoconstrictors have been reported in those disease states. Such observations have led to the attractive hypothesis that enhanced constriction in vascular disease results from attenuate NO‐induced dilatation. However, whilst there is some evidence that pathological impairment of endothelial function is accompanied by increased constrictor activity, particularly where serotonergic mechanisms are involved, it is inappropriate to make the general assumption that where disease impairs NO activity there will also be increased sensitivity to all constrictor stimuli.
HAEMODYNAMIC RESPONSES TO RAT ADRENOMEDULLIN IN ANAESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Ishiyama Yuichiro , Kitamura Kazuo , Ichiki Yoshinari , Sakata Junichiro , Kida Osamu , † Kenji Kangawa , Eto Tanenao 
Published: June 2007

SUMMARY1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive peptide, were examined in anaesthetized 16–18 week old spontaneously hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY).2. An intravenous injection of rat AM dose‐dependently reduced the mean blood pressure (MBP) with a concomitant fall in total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in both strains of rats. Per cent changes in MBP, TPRI and CI were not different between SHR and WKY.3. The plasma half‐life of rat AM in SHR was similar to that in WKY when it was administered at the dose of 1.0 nmol/kg.4. These findings indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The haemodynamic responsiveness to exogenous AM and its pharmaeokinetics in SHR were comparable with those in WKY.
CILIARY ULTRASTRUCTURE AND BEATING ACTIVITY IN RAT AND GUINEA‐PIG RESPIRATORY MUCOSA
Authors: Joki Susanna , Toskala Elina , Saano Veijo , † Juhani Nuutinen 
Published: June 2007

SUMMARY1. The rat and the guinea‐pig are commonly used animals when the effects of drugs on ciliary activity in respiratory airways are studied. There are few data concerning the possible differences in ciliary function between these two animals.2. Using a photodetector method we measured the ciliary beating frequency (CBF) from the upper part of the trachea, the lower part of the trachea and the distal part of the main bronchi (subsegmental bronchi) of rat and guinea‐pig respiratory tract. In addition, the structure of the cilia was studied using scanning electron microscopy (SEM).3. CBF in the rat respiratory tract was significantly lower than in the guinea‐pigs. In the upper trachea, the CBF for rat was 12.7 beats/s and 15.3 beats/s for guinea‐pig. The respective values were 9.2/16.0 beats/s in the lower part of the trachea and 6.9/13.8 beats/s in subsegmental bronchi. In both rats and guinea‐pigs CBF was lower in the subsegmental bronchi than in the trachea (rat: 25.0–45.7%, guinea‐pig: 9.8–13.8%).4. In addition to higher CBF, the quality of the photo‐electrical signal was better from guinea‐pig tissues, probably as a result of the larger amounts of ciliated cells and longer cilia of guinea‐pig respiratory epithelia compared to those in rat mucosa.5. SEM showed that the rat cilia were on average shorter (3.6 vs 4.3 μm) and thinner (0.19 vs 0.22 μm) than those of the guinea‐pig. Rat mucosa was markedly less ciliated than the respiratory mucosa of the guinea‐pig.6. Choice of animal species may affect the reliability and sensitivity of results when drug effects on ciliary function are studied. Guinea‐pig may be the most suitable choice as a laboratory animal, although guinea‐pig mucosa requires more careful handling than rat tissue in order to avoid mechanical artefacts.
WHOLE BODY AND RENAL NORADRENALINE RELEASE DURING ACUTE INFUSION OF ENDOTHELIN‐1 IN CONSCIOUS SHEEP
Authors: Mathai Michael L. , Whitworth Judith A. , McDougall John G. 
Published: June 2007

SUMMARY1. The present study investigated in conscious sheep the response of the sympathetic nervous system to a systemic infusion of 20 nmol/h endothelin‐1 (ET‐l), using a tritiated‐noradrenaline (NA) tracer dilution technique.2. Mean arterial pressure increased from 79 ±3 mmHg to a maximal level of 102± 12 mmHg by 30 min of ET‐1 infusion.3. Total and renal NA kinetics were measured during this time. Total NA spillover was not affected by infusion of ET‐1. In contrast, renal NA spillover decreased from a control level of 81 ± 5 to 30 ± 14ng/min (P<0.01) after 20 min and to 27 ± 7ng/min (P<0.01) after 30 min of ET‐1 infusion.4. The present findings are consistent with the proposal that a direct vasoconstrictor action of ET‐1 results in a paroreflex mediated reduction in renal sympathetic vasoconstrictor activity.
THE PROPORTIONAL CUMULATIVE AREA UNDER THE CURVE OF PARACETAMOL USED AS AN INDEX OF GASTRIC EMPTYING IN DIABETIC PATIENTS WITH SYMPTOMS OF GASTROPARESIS
Authors: van Wyk M. , Sommers De K. , Snyman J. R. , Moncrieff J. 
Published: June 2007

SUMMARY1. The foreshortened 2 h method of measuring liquid gastric emptying (i.e. the proportional cumulative area under the curve of paracetamol) was utilized in diabetic patients in order to detect both gastroparesis and the influence of metoclo‐pramide, a known prokinetic drug, on this condition.2. Metoclopramide, 10 mg intravenously, caused a significant increase in the median PCAUC from 20 min onwards.3. In this study delayed gastric emptying was defined as a %PCAUC without pretreatment lower than the 5% percentile at 40, 60 and 90 min for normal volunteers. According to this criterion seven of the 10 patients with clinical symptoms of gastroparesis and/or peripheral neuropathy had delayed gastric emptying.4. The PCAUC method would therefore seem to be a reliable model for investigating gastric emptying in diabetics and the effects of various prokinetic drugs on this condition.
INCREASED BLOOD PRESSURE AND CHANGES IN MEMBRANE LIPIDS ASSOCIATED WITH CHRONIC ETHANOL TREATMENT OF RATS
Authors: Puddey I. B. , Burke V. , Croft K. , Beilin L. J. 
Published: June 2007

SUMMARY1. Changes in membrane fluidity have been proposed to contribute to the pathogenesis of ethanol‐induced hypertension possibly through changes in membrane lipid patterns, but reports are inconsistent.2. In a controlled trial we documented ethanol‐induced changes in blood pressure and composition of membrane lipids in ethanol‐fed rats.3. Systolic blood pressure increased significantly in the ethanol‐treated rats (9.3 mmHg, s.e.m. 2.9) compared with the control group (—1.3 mmHg, s.e.m. 2.6). Mean cholesterol content in red cell membranes did not differ significantly between ethanol‐fed and control rats. Phospholipids of aorta, red cells and kidney showed a significant decrease in the polyunsaturated to saturated fatty acid ratio, while membrane phospholipids from the heart showed a significant increase in the polyunsaturated to saturated fatty acid ratio with ethanol treatment.4. In univariate regression blood pressure was significantly negatively related to levels of arachidonic acid in the kidney (P= 0.0013) and to linoleic acid in the aorta (P= 0.0341) and red cells (P= 0.0289). Blood pressure was not significantly related to fatty acids in the heart nor to membrane cholesterol or phospholipids.5. Differences in fatty acid composition of phospholipids between controls and ethanol‐fed rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved in ethanol‐induced hypertension.
EFFECT OF AN ANTIHYPERTENSIVE DRUG ON BRAIN ANGIOTENSIN II LEVELS IN RENAL AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Morishita Ryuichi , Higaki Jitsuo , Nakamura Yoshio , Aoki Motokuni , Yamada Kazuo , Moriguchi Atsushi , Rakugi Hiromi , Tomita Naruya , Tomita Sawako , Yu Hisahiro , Nakamura Fumiaki , Mikami Hiroshi , Ogihara Toshio 
Published: June 2007

SUMMARY1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain All. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma All in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two‐kidney, one‐clip (2K1C) and spontaneously hypertensive (SHR) rats.2. Hydralazine (20mg/kg per day) and vehicle (water) were given to 2K1C rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition, vehicle was applied to sham operated rats and Wistar‐Kyoto (WKY) rats. Brain and plasma AII was measured by a highly sensitive radioimmunoassay coupled with high performance liquid chromatography.3. Hydralazine treatment effectively lowered blood pressure to the same levei of sham‐operated and WKY rats. 2K1C rats showed significantly higher plasma All than sham rats, but hydralazine treatment did not show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats showed a significantly higher level than sham rats. Interestingly, hydralazine treatment diminished this increase in brain AII. In contrast, SHR showed higher brain A11 levels in the hypothalamus, brainstem and cerebellum than in WKY rats, whereas there was no significant change in plasma AII concentration between SHR and WKY rats. In contrast to the results found in 2K1C rat experiments, hydralazine treatment failed to decrease brain AII levels despite lowered blood pressure.4. In conclusion, brain AII is affected by systemic blood pressure in 2K1C hypertensive rats, but not in SHR, and the mechanisms which cause the difference between 2K1C rats and SHR are unknown in this study.
COMPARISON OF THE ATTENUATING EFFECTS OF FOUR β‐ADRENOCEPTOR AGONISTS ON RAT ISOLATED UTERUS AND AORTA
Authors: Doggrell Sheila A. 
Published: June 2007

SUMMARY1. The ability of four 8‐adrenoceptor agonists to attenuate oxytocin (0.2,2 and 20 nmol/L) or KCI (20,40 and 80 mmol/L)‐induced Contractions of the uterus (n= 5–8 for each agonist) and the KCI (18 mmol/L)‐induced contractions of the aorta (n = 9 for each agonist) from rats, pretreated with oestradiol has been compared.2. Isoprenaline, salbutamol, terbutaline and procaterol (0.1–10μmol/L) attenuated the contractions of the uterus and the aorta. All four agonists had similar attenuating potencies on the uterus.3. Procaterol caused the same maximal attenuation (33%) on the aorta as the other β‐adrenoceptor agonists and is thus acting as a full β2‐adrenoceptor agonist under these experimental conditions. Isoprenaline and procaterol were much more potent than salbutamol and terbutaline in attenuating the aorta responses.4. This study showed that isoprenaline and procaterol were potent attenuants on both the uterus and aorta whereas salbutamol and terbutaline were potent uterine but only modest aorta attenuants. This preliminary study indicates that the responsiveness of uterine and vascular tissue to certain β2‐adrenoceptors differs.
MOLECULAR AND FUNCTIONAL DIVERSITY OF K+ CHANNELS
Authors: Christie MacDonald J. 
Published: June 2007

SUMMARY1. Amino acid sequences encoding K+ channels belong to several subfamilies of the voltage‐gated ion channel superfamily which includes Na2+‐, Ca2+‐, and cyclic nucleotide gated channels. The Kv family is the largest group, and encodes delayed rectifier, A‐type, and large conductance Ca2+ activated K+ channels.2. The α‐subunits of Kv channels form as tetramers of four independent subunits. Each subunit has six membrane spanning regions and a pore forming ‘P’ region. Subunits belong to subfamilies (Kv1–4, BK, Eag) comprising multiple members, each of which has distinct properties resembling each of the major types of native Kv channel when expressed as homomultimers in heterologous systems.3. Enormous diversity of Kv channel function arises from the multiplicity of subunits, the formation of heteromultimers within subfamilies and from association with intracellular β‐subunit proteins.4. In the absence of direct structural information, mutational analyses have provided considerable insights into the structure of the voltage‐sensor, pore‐forming region and the sites of action of drugs, toxins and associated proteins.5. Another subfamily, the inwardly rectifying, or KIR, family, appears to have arisen from a deletion of the first four membrane spanning regions of ancient Kv channels, changing gating properties from outward to inward rectification. These include the G‐protein gated inward rectifiers and Katp channels.
ACETYLCHOLINE RECEPTORS AND THE CYTOSKELETAL CONNECTION
Authors: Phillips William D. 
Published: June 2007

SUMMARY1. The post‐synaptic membranes of neurons and muscle cells are characterized by clusters of transmitter receptors, the number and type of which help to determine synaptic efficacy. Here I briefly review what is known of the mechanism of clustering of nicotinic acetylcholine receptors (AChR) at neuromuscular synapses.2. The extracellular protein agrin is thought to be secreted by the motor nerve terminal and trigger localized clustering of AChR in the post‐synaptic membrane of the skeletal muscle cell.3. Binding of agrin to its receptor, α‐dystroglycan, is followed by rearrangements of the muscle membrane cytoskeleton with localized replacement of dystrophin by utrophin. It remains unclear how these changes relate to the clustering of AChR.4. In separate studies, RAPsyn/43k protein, a protein associated with the inner face of the post‐synaptic membrane was shown to be able to cluster AChR and link them to the cytoskeleton when both proteins were co‐transfected into fibroblasts.5. Mutational studies on RAPsyn identified putative binding domains for AChR and for the cytoskeleton within the RAPsyn primary structure. Targeted disruption of the RAPsyn gene in mice prevented post‐synaptic AChR clustering and led to neonatal lethality. Thus RAPsyn might be the final link in the pathway that leads to AChR immobilization in the post‐synaptic membrane.6. The recent observation that active forms of agrin are not restricted to cholinergic regions of the brain suggests that analogous pathways may exist for clustering other receptor types.
SOME PHYSIOLOGICAL OUTCOMES OF RENIN GENE STUDIES
Authors: Moris Brian J. 
Published: June 2007

SUMMARY1. The cloning of the renin gene has permitted studies of its physiological regulation, extrarenal expression and role in disease.2. Marked modulation of renin mRNA concentration is seen in adrenal, heart and hypothalamus in response to sodium depletion and inhibition of A11 formation, as well as in models of renal and genetic hypertension in the rat.3. One important outcome of studies of the promoter has been the discovery of a cyclic AMP‐responsive sequence.4. Sequence variations have been detected in or near the renin gene and have been used as markers in studies of its role in cardiovascular disease aetiology.5. In conclusion, molecular biology has, in the past decade, made a significant contribution to the understanding of renin physiology and pathophysiology.
EFFECTS OF GAMMA‐AMINOBUTYRIC ACID ON REGIONAL VASCULAR RESISTANCES OF CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Takemoto Yumi 
Published: June 2007

Summary1. The regional vascular effects of a central injection of gamma‐aminobutyric acid (GABA) in conscious spontaneously hypertensive rats (SHR) were compared with normotensive control rats (NCR), including Wistar‐Kyoto rats (male, 10–20 weeks of age). One week or more after insertion of a cannula into the cisterna magna, an electromagnetic flow probe was implanted around one of five arteries, and a catheter for measurement of blood pressure and heart rate was inserted into the terminal aorta or common carotid artery. Cardiovascular changes were observed in the conscious animal after recovery from the surgery. Peripheral resistance was calculated as pressure divided by flow.2. Ten min following intracisternal injection of 10μmol of GABA, mean arterial pressure and heart rate were significantly lowered (P < 0.05; t‐test): ‐ 29 and ‐ 16% (70 d.f.) in SHR versus ‐ 23 (116 d.f.) and ‐19% (112 d.f.) in NCR. Hindquarters, carotid, superior mesenteric and renal, but not coeliac, vascular resistances were significantly lowered (P < 0.05; t‐test, 21, 9, 18 d.f.) in SHR. However, when comparing the effect of GABA injection in SHR and NCR, there were no significant differences in coeliac, carotid and hindquarters vascular resistances, but there were significant decreases in superior mesenteric and renal vascular resistances in SHR.3. These results indicate that: (i) a cisternal injection of GABA in SHR decreases both peripheral vascular resistance and heart rate, and thereby lowers blood pressure; (ii) the vascular resistance of the superior mesenteric and renal vascular beds was more decreased in SHR than in NCR. This suggests that the GABAergic control of regional vascular resistance differs in the SHR and the NCR.
CORRELATION ANALYSIS OF BLOOD PRESSURE AND PLATELET AGGREGATION/VASCULAR REACTIVITY IN SHRSP, WKY, F1 AND BACKCROSS GENERATIONS
Authors: Hamano Megumi , Mashiko Satoshi , Onda Takeshi , Tomita Isao , Tomita Takako 
Published: June 2007

Summary1. Hypofunction of stroke‐prone spontaneously hypertensive rat (SHRSP) platelets at developmental ages of hypertension is due to the defective protein (p47) phosphorylation which is mediated by protein kinase C. This study was undertaken to examine the genetic association of platelet functions and vascular reactivity with hypertension using male WKY, SHRSP, F1 and backcross generations at 16–18 weeks of age.2. The distribution of blood pressure was continuous in each generation.3. Contraction of mesenteric vascular bed with norepin‐ephrine was positively correlated with blood pressure in the five generations (r = 0.77, n= 128).4. Thrombin‐induced platelet aggregation was inversely correlated with blood pressure (r =−0.87, n= 127).5. The distribution of platelet aggregation and contraction was continuous in each generation, and backcross generations were not likely to have 1:1 segregation.6. These results suggest the possibility that platelet hypo‐aggregability and peripheral vascular resistance are due to the pleiotropic effect of hypertensive genes, or that genes controlling these three characters are closely linked each other.
CALCITONIN GENE‐RELATED PEPTIDE‐INDUCED RELAXATION IN ISOLATED SMALL SUPERIOR MESENTERIC ARTERIES FROM ADULT STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Gao Y. J. , Nishimura Y. , Suzuki A. , Nakai Y. 
Published: June 2007

Summary1. The relaxant responses to calcitonin gene‐related peptide (CGRP) of the 3rd order branches of the superior mesenteric arteries (SMA) from 6 month old stroke‐prone spontaneously hypertensive rats (SHRSP) and age‐matched Wistar‐Kyoto (WKY) rats were studied in vitro.2. Cumulative addition of CGRP (10‐11‐10‐7 mol/L) caused endothelium‐independent relaxation of arterial rings precontracted with noradrenaline (10‐6 mol/L). A markedly increased response to CGRP was observed in SHRSP.3. There was no significant difference between SHRSP and WKY in relaxation produced by forskolin, dibutyryl cyclic AMP and 3‐isobutyl‐1‐methylxanthine.4. Pretreatment with glibenclamide (10‐6 mol/L) did not affect CGRP‐induced relaxation in either SHRSP or WKY.5. These results indicated that CGRP‐induced vasodilation was increased in the small branches of SMA from SHRSP, and that this increase did not seem to be associated with an augmented response to cyclic AMP or with increased involvement of ATP‐sensitive potassium channels.
ALTERED SIGNALLING IN VASCULAR SMOOTH MUSCLE FROM SPONTANEOUSLY HYPERTENSIVE RATS MAY LINK MEDIAL HYPERTROPHY, VESSEL HYPERINNERVATION AND ELEVATED NERVE GROWTH FACTOR
Authors: Tuttle Jeremy B. , Spitsbergen John M. , Stewart Jeanine S. , McCarty Richard M. , Steers William D. 
Published: June 2007

Summary1. Secretion of nerve growth factor (NGF) by cultured vascular smooth muscle cells (VSMC) derived from spontaneously hypertensive rats (SHR) and the normotensive Wistar‐Kyoto (WKY) strain was measured via two site immuno‐assay (ELISA).2. Basal NGF secretion rates of quiescent SHR VSMC in serum‐free culture medium were elevated compared to similar WKY VSMC.3. SHR VSMC displayed increased NGF secretion in response to activation of sympathetic neurotransmitter receptors while VSMC of WKY were largely unresponsive to the agents (phenylephrine, isoproterenol, alpha‐beta‐methyl ATP, neuro‐peptide Y).4. Mitogenic stimulation with platelet‐derived growth factor (PDGF) raised SHR NGF secretion rates almost three times more than PDGF increased WKY secretion.5. SHR VSMC also failed to demonstrate normal inhibitory control over NGF secretion seen in WKY and previously in Sprague‐Dawley and Wistar strain VSMC with adenylate cyclase activation and down‐regulation of protein kinase C. High concentrations of forskolin stimulated, instead of inhibiting, secretion in SHR. Stimulation was also seen after pre‐treatment with phorbol ester for 24 h while this inhibited secretion in the WKY.6. These results confirm that the SHR VSMC are hyper‐responsive to growth stimuli such as contractile agonists and mitogens. This hyperresponsiveness includes an abnormal control over NGF secretion such that normally inhibitory treatments stimulate NGF output in the SHR.7. Because the SHR demonstrates important defects in the major intracellular growth‐signalling systems that also regulate NGF output and vessel innervation, the predicted result of the defects is a destructive feed‐forward cycle of growth and innervation. This is the SHR phenotype in vivo.
DISTINCT EXPRESSION OF TRANSFORMING GROWTH FACTOR‐β RECEPTOR SUBTYPES ON VASCULAR SMOOTH MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR‐KYOTO RATS
Authors: Fukuda Noboru , Kubo Atsushi , Izumi Yoichi , Soma Masayoshi , Kanmatsuse Katsuo 
Published: June 2007

Summary1. We investigated the characteristics and expression of transforming growth factor‐β (TGFB) receptor subtypes on vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats.2. TGF β binding assays revealed that VSMC from SHR showed higher number and affinity of TGF β receptors than cells from WKY rats.3. The affinity labelling with [125I]‐TGFβ1 revealed the presence of TGFβ receptor subtypes with molecular sizes of 280, 85, 70 and 60kDa on VSMC from both strains at high cell density. The abundance of the 85 kDa receptor subtype was greater in VSMC from SHR than cells from WKY rats. The 85 kDa receptor subtype was not detected on VSMC from both strains at low cell density.4. These results suggest distinct expression of TGFP receptor subtypes on VSMC from SHR and WKY rats, which may account for the exaggerated proliferative response of VSMC from SHR to TGFβ.