bluuebunny/crossref_metadata_2025_split huggingface dataset:
MECHANISMS FOR PRESERVED CEREBROVASCULAR AUTOREGULATION DURING HYPERTENSION IN RATS AFTER SINOAORTIC DENERVATION
Authors: Talman W. T. , Dragon D. Nitschke 
Published: June 2007

Summary1. Cerebral blood flow (CBF) and cerebrovascular resistance (CVR) autoregulate to higher levels of arterial pressure (AP) in rats after sinoaortic denervation (SAD) than in intact rats.2. Potential mechanisms for this phenomenon were studied by monitoring CBF by laser flowmetry while increasing AP in rats after: (i) SAD; (ii) SAD plus bilateral removal of the superior cervical ganglia; (iii) SAD plus interruption of all renal vessels and nerves (renal isolation); (iv) SAD plus sympathectomy and renal isolation; and (v) intravenous treatment with the nitric oxide synthase inhibitor L‐nitroarginine (LNA).3. Compared to intact control rats autoregulation persisted to higher absolute levels of AP in SAD rats with isolation of the kidneys and resistance did not fall significantly below that in rats with SAD alone.4. Effects of SAD on autoregulation were not altered by combining renal isolation with an interruption of sympathetics.5. LNA did not affect the baroreflex but blocked a breakthrough of autoregulation even at a maximal mean AP (MAP) of 189 ± 2mmHg.6. Breakthrough occurred in animals pretreated with LNA plus L‐arginine but not in animals given LNA plus D‐arginine.7. These data are consistent with a role of the baroreflex in the expression of breakthrough and suggest that breakthrough may result from release of nitric oxide or a nitric oxide donor.
MONITORING NOREPINEPHRINE LEVELS BY MICRODIALYSIS IN THE WHITE ADIPOSE TISSUE OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Cabassi A. , Bergamaschi E. , Mutti A. , Franchini I. , Borghetti A. 
Published: June 2007

Summary1. To investigate whether microdialysis is suitable to monitor catecholamine in white adipose tissue of conscious rat and to assess eventual differences in norepinephrine (NE) interstitial levels, two groups of 12 male spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats, 14–16 weeks old, were compared.2. A flexible microdialysis probe was implanted subcutaneously in the parascapular region, and perfused with Ringer solution (flow rate: 2.0 μL/min). After a 20min equilibration period, NE levels were monitored over a 120 min period; then, tyramine hydrochloride (0.1 nmol/min) was perfused for 80 min. Dialysates from each 20 min collection period were analysed by HPLC with electrochemical detection for NE.3. Basal levels of NE (adjusted for the recovery) were higher in SHR compared to WKY (1210.0 ± 140.5 pg/mL dialysate vs 573.3 ± 75.8 pg/mL dialysate; P < 0.001, ANOVA). In both strains tyramine perfusion increased NE concentration in dialysates; the net (i.e. baseline subtracted) NE output was lower (76.3 pg/h, s.e.m. 22.3) in SHR compared with that shown by WKY rats (201.0 pg/h, s.e.m 18.4, P < 0.01).4. The increased basal levels of NE observed in SHR are associated with a blunted response to tyramine challenge. Since tyramine is known to cause NE release from the cytosol but not from vesicle stores, such a blunted response is consistent with an increased turnover rate of NE or with an accelerated uptake in pre‐synaptic vesicles which, together with the higher basal levels, would suggest increased noradrenergic activity.
CYCLOSPORINE A‐INDUCED HYPERTENSION IN SHR AND WKY: ROLE OF THE SYMPATHO‐ADRENAL SYSTEM
Authors: Grobecker H. F. , Riebel K. , Wellenhofer T. 
Published: June 2007

Summary1. Cyclosporine A induced a highly significant additional increase in blood pressure in spontaneously hypertensive rats (SHR) and elevated clearly the blood pressure in the genetically related normotensive controls, Wistar‐Kyoto (WKY) rats, after both single (i.v.) and long‐term administration (oral).2. Acceleration of rise in blood pressure by cyclosporine is caused by sympatho‐adrenal activation. Evidence for this mechanism of action came from the following pharmacological interventions: After chemical sympathectomy with 6‐hydroxydopamine increase in blood pressure by cyclosporine was significantly reduced. Depletion of catecholamine stores by reserpine also diminished significantly the cyclosporine induced hypertension. Selective cyladrenergic receptor blockade by prazosin blunted acute hypertension induced by cyclosporine.3. Norepinephrine concentrations in the spleen of both WKY and SHR were reduced by long‐term administration of cyclosporine. In the kidneys of WKY rats the level of norepinephrine was decreased but increased in the kidneys of SHR after long‐term administration of cyclosporine.4. Also the immunosuppressive agent FK506 with a macrolide‐like structure induced acute hypertension in normotensive rats. The hypertensive effect was blunted by the vasoselective calcium channel blocker felodipine.5. It is concluded that immunosuppressive agents like cyclosporine or FK506 activate the sympatho‐adrenal system in normotensive and genetically hypertensive rats, thereby inducing hypertension. The mechanism of action may contribute to the hypertension seen in patients treated with cyclosporine after transplantation of heart, kidney or liver.
CURRENT STATUS OF PUTATIVE IMIDAZOLINE (I1) RECEPTORS AND RENAL MECHANISMS IN RELATION TO THEIR ANTIHYPERTENSIVE THERAPEUTIC POTENTIAL
Authors: Evans Roger G. 
Published: June 2007

SUMMARY1. A ‘second generation’ of centrally acting antihypertensive agents has recently been developed. Unlike the ‘first generation’ of these agents (e.g. α‐methylodopa, clonidine, guanabenz), which act predominantly by an agonist action at α‐adrenoceptors, these agents (e.g. rilmenidine, moxonidine) are believed to exert their antihypertensive effects chiefly by an interaction at putative imidazoline (I) receptors of the I1‐type, and so have a reduced profile of α‐adrenoceptor‐mediated side effects. There is also evidence from studies in experimental animals that activation of I1‐receptors mediates a natriuretic effect. This review evaluates the evidence that they mediate renal effects different from those of α‐adrenoceptors that could contribute to their long‐term efficacy.2. Data from binding studies suggest that I1‐binding sites are heterogeneous. There is conflicting evidence concerning whether any of there binding sites are truly receptors. Indeed, the best evidence for the existence of I1‐receptors comes from in vivo experiments receptive sites in the central nervous system to reduce sympathetic drive and blood pressure.3. There are a wide range of potential sites and mechanisms through which centrally acting antihypetensive agents can affect renal function, including actions mediated within the central nervous system, heart, systemic circulation and within the kidneys themselves. ‘First generation’ centrally acting anti‐hypertensive agents cause diuresis and natriuresis in rats, while in dogs and humans a diuresis is often seen with variable effects on sodium excretion.4. Evidence from studies in anaesthetized rats indicates that rilmenidine and moxonidine can promote sodium excretion by interacting with both central nervous system and renal putative I1‐receptors. This does not appear to necessarily be the case in other species. At this time there are few or no published data from clinical studies to suggest that ‘second generation’ centrally acting antihypertensive agents affect salt and water balance differently from ‘first generation’ agents.
BAROREFLEX CONTROL OF CORONARY BLOOD FLOW VARIES REGIONALLY IN AWAKE DOGS
Authors: Quail Anthony W. , Cottee David BF , White Saxon W. , Proges William L. , Hennessy Edmund J. 
Published: June 2007

SUMMARY1. Baroreflex responses to changes in aortic pressure were measured simulataneously in three main coronary regions of awake dogs.2. Pulsed Doppler flow probes were mounted at prior surgery on the right, circumflex and anterior descending coronary arteries; the animals were placed in complete heart block and the left ventricle was placed. After 2‐4 weeks recovery, baroreflexes were evoked by inflating a balloon catheter placed in the mid‐thoracic aorta via the femoral arteriotomy. Flow and pressure data were collected at rest, and during acute (8 s) and steady‐state (25 s) baroreflex challenge.3. Changing ventricular rate alone caused a fall in aortic pressure at low rates; however, over the range 60 to 180 b.p.m., circumflex and anterior descending coronary flow and conductance changed directly with ventricular rate, but right coronary flow and conductance remained unchanged.4. Acute aortic pressure elevation increased flow at 8 s in all beds at all rates. Conductance effects at 60 b.p.m. were negligible in all three beds, but rose at 100 and 180 b.p.m. in the right and circumflex beds.5. Sustained aortic pressure elevation (25 s) caused flow to return towards control in all beds at all ventricular rates, but in the right coronary at 60 b.p.m. flow fell below control. Conductance at this time was unchanged at all rates in the anterior descending bed, fell modestly in the circumflex, and decreased to below resting in the right coronary bed.6. Baroreflex control of coronary flow and conductance thus varies between territories, and within territories, depending on ventricular rate. The right coronary bed appears to be regulated by a bidirectional, baroreflex‐linked mechanism, which is functionally opposite in action to that found in most vascular beds.
PHENYTOIN‐INDUCED HYPERGLYCAEMIA MAY CONFOUND RAT CEREBROPROTECTION MODELS
Authors: Qi Hui , Newman George C. 
Published: June 2007

SUMMARY1. The anticonvulsant phenytoin (PHT) has been used with variable success in animal models of cerebral ischaemia. Although PHT has been reported to alter glucose regulation in man, this potential effect has been largely ignored in animals. Because hyperglycaemia strongly influences the outcome of cerebral ischaemia, we sought to systematically delineate the effects of PHT on serum glucose in several rat strains.2. We have studied the PHT dose‐response curve for serum PHT and glucose concentrations and several physiological variables. Phenytoin induces a significant, concentration‐dependent hyperglycaemia, even in the ranges commonly used for humans and in animal models.3. Hypothermia of several degrees was observed during PHT administration, but no hypotension or bradycardia was found.4. Both hyperglycaemia and hypothermia must be considered when PHT is studied as a neuroprotective agent in animal models.
FUNCTIONAL IMAGING STUDIES OF HUMAN VISUAL CORTEX
Authors: Watson John DG 
Published: June 2007

SUMMARY1. The past decade has seen a burgeoning of functional imaging studies of cerebral activity in normal humans. Much of this work has been performed on the visual system, which is an important and often conveniently studied part of the brain.2. Previously, what we believed about the functional anatomy of the human visual system was almost entirely obtained by studying individual patients with cerebral lesions and from experiments in animals. Early functional imaging experiments were often quite simple, descriptive exercises.3. Techniques such as positron emission tomography have become quite mature; with this and increasing experience on the part of the investigators, the experiments performed have become more novel. Functional imaging methods have become part of the mainstream of investigations to be used for research on vision. They already have led to novel hypotheses about how aspects of this system work.
INJURY‐ AND USE‐RELATED PLASTICITY IN THE PRIMARY SENSORY CORTEX OF ADULT MAMMALS: POSSIBLE RELATIONSHIP TO PERCEPTUAL LEARNING
Authors: Irvine DRF , Rajan R. 
Published: June 2007

SUMMARY1. Restricted cochlear lesions in adult animals result in a reorganization of auditory cortex such that the cortical region deprived of its normal input by the lesion is occupied by expanded representations of adjacent cochlear loci (and thus of the frequencies represented at those loci). Analogous injury‐induced reorganization is seen in somatosensory, visual and motor cortices of adult animals after restricted peripheral lesions.2. Rather than constituting a central compensation for the peripheral loss, such reorganization appears to be an extreme form of changes in cortical organization that occur as a consequence of altered patterns of input such as arise from differential use of restricted regions of receptor surfaces (‘userelated’ reorganization). Thus, the frequency organization of auditory cortex is modified in animals trained to perform a frequency discrimination task and analogous changes in the frequency selectivity of cortical neurons are produced by classical conditioning procedures.3. Recent evidence from the visual system suggests that changes similar to those involved in injury‐ and use‐related cortical reorganization may underlie some forms of what has been called ‘perceptual learning', the improvement in sensory/ perceptual discriminative performance with practice. Some forms of such learning are highly specific to the particular stimuli used in training (i.e. do not generalize to other stimuli), suggesting that the improved performance reflects a change in neural circuitry at a relatively early level of sensory processing. The limited available evidence supports the occurrence of such learning in the auditory system.4. Recent studies using functional imaging and related techniques indicate that injury‐ and use‐related reorganization occurs in human sensory and motor cortex.
RENAL TRANSPORT OF DRUGS: SPECIFICITY AND MOLECULAR MECHANISMS
Authors: Somogyi Andrew 
Published: June 2007

SUMMARY1. The kidney is principally an excretory organ for drugs and their metabolites and has developed high capacity transport systems to rapidly eliminate the large quantities of foreign compounds delivered to it.2. There are specific and selective transporters for organic cations and organic anions at the contraluminal and luminal membranes of the epithelial cells lining the proximal tubule.3. For organic anions, the transporter (termed PAH‐transporter) is located at the contraluminal cell membrane and uptake is a tertiary active transport process. Important physicochemical properties for interaction with this transporter are hydrophobicity, ionic charge strength and electron‐attracting side groups.4. For organic cations, there is evidence for one common transport system at the contraluminal membrane and substrate requirements are the degree of hydrophobicity, ionic charge strength and hydrogen bond formation. At the luminal membrane, an electroneutral H+/organic cation exchanger in which the degree of substrate hydrophobicity is critical for interaction and a choline transport system have been described.5. P‐Glycoprotein present in renal brush border membranes transports organic cationic drugs but is dissimilar to the luminal electroneutral H+/organic cation exchanger.6. Clinically, several drugs have been implicated in causing interactions via these transport systems. For organic anions, probenecid blocks the tubular secretion of other organic anions and this has been used to prolong the duration of action of penicillin‐like compounds. For organic cations, cimetidine and trimethoprim are potent inhibitors of the secretion of a number of organic cations, particularly procainamide, which can result in significant clinical toxicity.7. An understanding of the mechanisms of renal tubular secretion of drugs and their metabolites will allow for the prediction of drug interactions involving renal excretory mechanisms.
IMIDAZOLINE BINDING SITES AND SIGNAL TRANSDUCTION PATHWAYS
Authors: Musgrave IF , Krautwurst D. , Schultz G. 
Published: June 2007

SUMMARY1. Discrete, non‐adrenergic binding sites for imidazolines have been characterized in the brain and periphery. The 11 clonidine‐preferring site is mainly distributed in the brain and brain stem, while the 12 idazoxan‐preferring site is more widely distributed.2. The 11 site appears to be associated with modulation of blood pressure. Imidazolines act within the rostral ventrolat ral medulla to produce hypotension. The underlying signal transduction mechanism is poorly understood.3. The imidazolines clonidine and cirazoline inhibited nicotine‐stimulated calcium entry into rat phaeochromocytoma (PC‐12) cells by a non‐adrenergic mechanism. This effect was not attributable to the stimulation of protein kinases.4. Similarly, clonidine and cirazoline inhibited nicotinestimulated inward currents into PC‐12 cells. This inhibitory action was not altered by inhibitors of signal transducing G‐proteins.5. Clonidine and cirazoline displaced the ion channel ligand [3H]‐phencyclidine from nicotinic acetylcholine receptors, suggesting that these drugs act by direct blockade of the intrinsic ion channel of the nicotinic acetylcholine receptor.6. This ion channel‐blocking activity represents a novel action of these imidazolines and may underlie some of the proposed physiological actions of 11 sites.
TRINUCLEOTIDE‐REPEAT EXPANSIONS AND NEURODEGENERATIVE DISEASE: A MECHANISM OF PATHOGENESIS*
Authors: Hannan Anthony J. 
Published: June 2007

SUMMARY1. Studies of a number of hereditary neurodegenerative diseases, the most common of which is Huntington's disease, have identified the expansion of trinucleotide repeats as a common causative mutation.2. The diseases are caused by expansions of CAG repeats, encoding polyglutamine tracts, within the coding regions of a variety of unrelated genes. The mechanism whereby this specific genetic instability leads to selective neurodegeneration is currently unknown.3. Our current understanding of these polyglutamine expansion neurodenerative diseases is outlined. A potential mechanism is discussed whereby subtle alterations in glutamine, and consequently glutamate levels, may induce chronic excitotoxicity and slow cell death in neuronal populations possessing specific glutamate receptors. The potential role of glutamate receptor‐mediated changes to intracellular calcium levels and energy metabolism in the neurodegenerative pathway is also addressed.
CARDIORESPIRATORY AND RENAL RESPONSES TO ARTERIAL CHEMORECEPTOR STIMULATION BY HYPOXIA OR ALMITRINE IN MEN
Authors: Brauer H. , Gens A. , Ledderhos C. , Sanchez R. , Schuster R. , Quies W. , Honig A. 
Published: June 2007

SUMMARY1. The cardiorespiratory and renal responses to 3h of normobaric whole‐body hypoxic hypoxia (F1O2= 0.12) as well as to arterial chemoreceptor stimulation by the oral administration of 100 mg almitrine bismesylate during normoxia were measured in 12 normotensive young men undergoing water diuresis. A third series of responses obtained under comparable conditions in the same subjects served as time controls.2. No significant changes could be detected over time in the parameters measured in control experiments. The subjects reacted to both whole‐body hypoxic hypoxia and to pharmacological chemoreceptor stimulation with significant increases in heart rate, tidal volume, minute ventilation and filtration fraction. Overall renal vascular resistance rose significantly in hypoxia; increases in renal vascular resistance in almitrine experiments were not significant.3. Renal fractional lithium excretion decreased significantly in response to whole‐body hypoxic hypoxia and increased slightly in response to almitrine. Fractional urine and sodium excretion showed negligible changes.4. The data indicate that, in humans, both almitrine and whole‐body hypoxic hypoxia affect not only alveolar ventilation but also renal haemodynamics.5. The renal electrolyte excretion pattern suggests that under certain circumstances (e.g. dilated renal vascular bed) acute, but well‐tolerated, whole‐body hypoxic hypixia can simultaneously stimulate renal proximal tubular sodium reabsorption and inhibit distal tubular sodium reabsorption. The renal tubular responses also indicate that almitrine may influence renal tubular lithium reabsorption by, thus far, unknown mechanisms.
COSEGREGATION OF THE NEW REGION ON CHROMOSOME 3 WITH SALT‐INDUCED HYPERTENSION IN FEMALE F2 PROGENY FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE AND WISTAR‐KYOTO RATS
Authors: Matsumoto Chiho , Nara Yasuo , Ikeda Katsumi , Tamada Tomoko , Mashimo Tomoji , Nabika Toru , Sawamura Makoto , Yamori Yukio 
Published: June 2007

SUMMARY1. We investigated candidate loci for salt‐sensitive high blood pressure (BP) in F2 progeny from crossing Wistar‐Kyoto and stroke‐prone spontaneously hypertensive rats.2. In female F2 progeny, systolic and diastolic BP on the 12th day and the seventh month after salt loading was strongly liked with the D3Mgh12 and D3Mgh6 loci on chromosome 3, respectively.3. These loci were linked with BP only in female F2 progeny, not in males.4. These results indicate that hormonal factors may influence salt sensitivity, particularly with respect to gender differences.
GAP JUNCTION CHANNELS GATING AND PERMSELECTIVITY: THERE ROLES IN CO‐ORDINATED TISSUE FUNCTION
Authors: Brink Peter R. 
Published: June 2007

SUMMARY1. The gating and permselective properties of gap junction channels are important parameters to determine in delineating their role in co‐ordinated tissue function. This is of particular relevance in non‐excitable tissues.2. In the present study gating characteristics of rCx43 are demonstrated. The mean open times are of the order of 0.45‐1.1 s. These values are extraordinarily large.3. The permselectivity of a variety of gap junction channels is also illustrated to show the poor selectivity properties of gap junctions and, hence, their potential to allow the permeation of second messenger molecules.4. Gating and permselectivity, along with diffusion modelling, produce a picture for gap junction channels that is consistent with physiologically relevant modulation or regulation of gap junction channel patency.
GAP JUNCTION INVOLVEMENT IN SECRETION: THE PANCREAS EXPERIENCE
Authors: Meda Paolo 
Published: June 2007

SUMMARY1. Gap junctions and junction‐mediated cell‐to‐cell communications are obligatory features of gland cells, whatever their secretory product is.2. Studies on pancreatic islets and acinar cells indicate that cell‐to‐cell communication via gap junction channels is required for proper biosynthesis, storage and release of both insulin and amylase.3. However, the endocrine and exocrine portions of the pancreas show opposite connexin (Cx) and coupling changes in relation to the activation and inhibition of their secretory functions.4. These differences may be accounted for by the expression of Cx43 in pancreatic islets and of Cx26 and Cx32 in pancreatic acini. This alternative expression of connexin isoforms is also found in several other endocrine and exocrine glands.5. These observations indicate that connexin‐made channels play a central role in the control of secretory events.