bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVIDENCE FOR IMPAIRED ENDOTHELIUM DEPENDENT VASODILATION IN EXPERIMENTAL LEFT VENTRICULAR DYSFUNCTION
Authors: Kaye David M. , Jennings Garry , Angus James A. 
Published: June 2007

SUMMARY1. The full range of vascular reactivity was investigated in the hindlimb circulation of conscious, autonomically blocked rabbits with experimental (adriamycin‐induced) cardiomyopathy.2. Adriamycin treatment caused a significant reduction in left ventricular systolic function, as assessed by echocardiography (left ventricular fractional shortening, controls vs adriamycin treatment; 36.7 ± 1.7%vs 27.3 ± 2.6%, P<0.05).3. Under pharmacological autonomic effector block, the range of the vasodilator response (resistance range, from resting to full vasodilatation) to acetylcholine was reduced by 41% (P<0.05) and by 37% for adenosine (P<0.05). Despite these changes the sensitivity (ED50) of the responses were unaltered.4. The ED50 of constrictor responses to noradrenaline and angiotensin II were similarly unaltered, in conjunction with a non‐significant attenuation of the constrictor‐response range.5. These results suggest that in this model of experimental left ventricular dysfunction, the capacity of the hindlimb circulation to respond to regionally infused endothelium dependent vasodilators is attenuated.
ANTISENSE OLIGONUCLEOTIDES: A NEW TOOL IN NEUROSCIENCE
Authors: Pilowsky Paul M. , Suzuki Satoshi , Minson Jane B. 
Published: June 2007

SUMMARY1. Recent studies have shown that gene expression can be selectively attenuated by administration of short sequences of nucleotides (oligonucleotides) that are complementary to a portion of messenger RNA coding for a particular gene product.2. This technique is known as ANTISENSE, because the oligonucleotides are complementary to the mRNA which has the same sequence as the SENSE strand of DNA.3. In the present review we focus, after a brief discussion of gene expression and mechanisms of action of ANTISENSE, on the methodological aspects of ANTISENSE experiments in neuroscience. In particular, we address the advantages, disadvantages and controls for the ANTISENSE technique, as well as the choice, design, mode of delivery, dose and storage of ANTISENSE oligonucleotides.
INFLUENCE OF α1‐ADRENOCEPTOR ANTAGONISM OF KETANSERIN ON THE NATURE OF ITS 5‐HT2 RECEPTOR ANTAGONISM
Authors: Marwood John F. 
Published: June 2007

SUMMARY1. In order to investigate α1‐adrenoceptor interactions with 5‐HT2 receptors, the effect of ketanserin (which antagonizes both types of the above receptors) on responses to 5‐hydroxytryptamine (5‐HT) and phenylephrine (PE) was measured in isolated perfused rat tail arteries.2. Ketanserin was found to be a competitive antagonist at 5‐HT2 receptors (pA2= 9.19) and α1‐adrenoceptors (pA2= 7.52).3. Ritanserin, an analogue of ketanserin with very weak α1‐adrenoceptor antagonist activity, was found to be a potent non‐competitive 5‐HT2 receptor antagonist.4. In the presence of the potent α1‐adrenoceptor antagonist prazosin, ketanserin was a non‐competitive 5‐HT2 receptor antagonist.5. Thus, for ketanserin to exhibit competitive 5‐HT2 receptor antagonism, its coexisting α1‐adrenoceptor antagonist property appears mandatory.
INVOLVEMENT OF TRANSFORMING GROWTH FACTOR‐β1 FOR PLATELETS‐INDUCED STIMULATION OF ENDOTHELIN‐1 PRODUCTION
Authors: Matsumura Yasuo , Murata Satoshi , Takada Kimi , Takaoka Masanori , Morimoto Shiro 
Published: June 2007

SUMMARY1. Possible mechanisms by which platelets stimulate the production of endothelin‐1 (ET‐1) in vascular endothelial cells (EC) were investigated.2. A supernatant of platelets stimulated the expression of prepro ET‐1 mRNA, followed by an increased secretion of ET‐1 from cultured EC. These responses were markedly enhanced by pretreatment of the platelets with thrombin, at a concentration which did not influence the ET‐1 production in EC. A platelet suspension, separated from cultured EC by a permeable nylon membrane, also markedly stimulated the ET‐1 secretion from EC.3. Endothelin‐1 production enhanced by the platelet supernatant, with or without thrombin pretreatment, correlated with the active transforming growth factor‐β1 (TGF‐β1) concentrations in the supernatant. The supernatant‐induced increase in ET‐1 secretion from the EC was markedly suppressed by TGF‐β1 neutralizing antibody.4. We tentatively conclude that platelets stimulate the endothelial ET‐1 production by releasing a bioactive diffusible substance, mainly TGF‐β1.
ACUTE TOXICITY OF BUPIVACAINE METABOLITES IN MICE
Authors: Bruguerolle B. , Attolini L. , Gantenbein M. 
Published: June 2007

SUMMARY1. This study was designed to document the acute toxicity of two metabolites of bupivacaine, desbutylbupivacaine (2,6, desbutylbupivacaine; PPX) and pipecolic acid in mice. All the compounds were administered by the intraperitoneal (i.p.) route.2. The mean convulsant activity was 100% for controls, 30, 100, 100, 100 and 90% for 400, 200, 150, 125 and 112.5 mg/kg i.p. of PPX, respectively, and 0% for the animals receiving pipecolic acid.3. The acute induced mortality was 60% for bupivacaine control group (50 mg/kg/i.p.), 60, 30 and 0% for 800, 400 and 200 mg/kg of pipecolic acid, respectively, and 100, 90, 60, 80 and 10% for 400, 200, 150, 125 and 112.5 mg/kg i.p. of PPX, respectively.4. The time to convulse was 158 ± 16 s for bupivacaine, 230 ± 30, 270 ± 24, 255 ± 21, 442 ± 84 and 418 ± 32 s for 200, 150, 125, 112.5 and 100 mg/kg i.p. of PPX, respectively; any pipecolic acid treated animal have convulsed.5. In conclusion, the present study demonstrated that PPX is more toxic than expected since we found that its induced mortality was approximately three times that found for bupivacaine and its CNS toxicity was about two times that of bupivacaine.
A NEW MODEL FOR THE GENERATION OF SYMPATHETIC NERVE ACTIVITY
Authors: Malpas Simon C. 
Published: June 2007

SUMMARY1. Sympathetic discharges from multifibre nerve recordings vary in their frequency of occurrence which displays both slow and fast rhythms and in their amplitude which reflects the number of activated fibres. It has been shown that the frequency of occurrence of these rhythms varies according to baroreceptor activity (via blood pressure and heart rate) while the number of activated fibres is independently affected by chemoreceptor activity.2. A new model is proposed for the generation of sympathetic nerve activity by the central nervous system to account for these results. The upper layer of the model comprises two oscillators, a fast and a slow cycle frequency oscillator, with the balance and occurrence maintained by afferent inputs such as the baroreceptors.3. It is hypothesized that two central oscillators impinge on a lower layer of the model influencing the number of activated fibres within each postganglionic sympathetic burst. This is independent of the frequency control and affected by separate afferent inputs such a chemoreceptors.
MINERALOCORTICOID AND GLYCYRRHIZIC ACID BLOCK STRESS INDUCED HYPOTENSION IN RATS
Authors: Ruszymah B. H. I. , Nabishah B. M. , Aminuddin S. , Khalid B. A. K. 
Published: June 2007

SUMMARY1. The aim of this study was to investigate the effect of repeated exposure to stress on tail blood pressure (TBP) of normal as well as GCA (glycyrrhizic acid) and steroid treated rats. Male Sprague‐Dawley rats (250 g) were exposed to ether vapour to achieve light anaesthesia prior to TBP recording. Rats were injected with either normal saline or naloxone prior to exposure to stress. Tail blood pressure was recorded daily for 2 weeks.2. We found that ether stress caused a transient drop in TBP in control as well as in dexamethasone (DEX) treated rats. The stress‐induced fall in blood pressure was reduced by naloxone in control rats but not in DEX treated rats. However the transient drop in TBP following stress was not seen in either GCA or deoxycorticosterone (DOC) treated rats.3. We conclude that first, the reduction in TBP was due to the release of endogenous opioids caused by stress. Second, DOC may block the release of such endogenous opioids, preventing the drop in TBP in response to stress, while DEX did not. Third, GCA caused a similar mineralocorticoid effect on reversing stress induced hypotension.
HISTORICAL PERSPECTIVE OF CARDIORENAL INTEGRATION
Authors: Henry James P. 
Published: June 2007

SUMMARY1. Early research on blood volume as an independent parameter affecting kidney function took the approach that the sensors must be located in the most compliant, that is the reservoir portion, of the cardiovascular system. This encompasses the great veins and the cardiac atria.2. Small changes in volume were shown not to affect the compliance of this reservoir and messages from the atrial receptor network were shown to travel in the vagus nerve and to control urine volume by antidiuretic hormone.3. Although greatly affected by the water immersion stimulus, sodium excretion was not as dependent on vagus integrity. The ensuing search for the natriuretic arm of the blood volume mechanism persisted for the next 20 years.4. Finally, one aspect of the elusive natriuretic factor was found exactly where theory had suggested, namely the most distensible part of the system, in specialized granules in the cardiac atria.
BRIEF REVIEW PAIN MECHANISMS AND MANAGEMENT: AN UPDATE
Authors: Siddall Philip J. , Cousins Michael J. 
Published: June 2007

SUMMARY1. Recent findings have further helped to elucidate the mechanisms involved in the transmission and modulation of pain. It is now known that pain, inflammation and nervous system damage result in a number of changes in peripheral nerves, spinal cord and supraspinal structures. These changes themselves may be responsible for the development and maintenance of chronic pain syndromes.2. In response to these findings, new agents and techniques have been applied in the clinical setting and new approaches have been developed to use existing agents more effectively. This review presents some of the findings from recent studies and the implications they have for the management of pain.
RENAL SYMPATHETIC AND HEART RATE BAROREFLEX FUNCTION IN CONSCIOUS AND ISOFLURANE ANAESTHETIZED NORMOTENSIVE AND CHRONICALLY HYPERTENSIVE RABBITS
Authors: Bell Leonard B. , Wilson Donald J. , Quandt Leslie M. , Kampine John P. 
Published: June 2007

SUMMARY1. Baroreflex control of heart rate (HR) has been studied in normotensive (NT) and hypertensive (HT) awake and anaesthetized animals and man, but baroreflex control of sympathetic nerve activity has not been well studied. We investigated baroreflex control of HR and renal sympathetic nerve activity (RSNA) over a wide range of arterial pressure (AP) in conscious and isoflurane (ISO) anaesthetized NT and HT rabbits.2. Animals were instrumented to record AP, HR and RSNA. Hypertension was accomplished by renal encapsulation. AP‐HR and AP‐RSNA baroreflex function curves were obtained while awake and after 1.0, 1.5, 2.0 and 2.5% ISO. All baroreflex curves were fit to sigmoid or exponential functions.3. In conscious rabbits, HT for 3–5 weeks, AP was significantly higher (75.6 ± 0.8 vs 102.3 ± 8.9 mmHg); HR significantly lower (218.0 ± 5.5 vs 189.5 ± 5.5 beats/min); and RSNA not different than NT rabbits (14.9 ± 2.2 vs 9.9 ± 3.2% max RSNA).4. ISO shifted AP‐HR and AP‐RSNA baroreflex curves to the left in NT and HT animals, and significantly attenuated baroreflex range and slope. At low ISO concentrations, baroreflex compensation for decreases in AP is limited to small increases in HR and sympathetic nerve activity. At higher ISO concentrations, baroreflex responses to decreases in AP are lost. RSNA responses to increases in AP are preserved with increasing ISO concentrations while HR responses are progressively attenuated. The sole effect of chronic hypertension was to shift the AP‐HR and AP‐RSNA barocurves to the right along the pressure axis in both conscious and ISO anaesthetized animals with no additional change in range or slope.5. At this stage of hypertension development, ISO anaesthesia affects baroreflex function equally in normotensive and hypertensive rabbits.
FORCE AND INTRACELLULAR Ca2+ DURING NANC‐MEDIATED RELAXATION OF RAT ANOCOCCYGEUS MUSCLE AND THE EFFECTS OF CYCLOPIAZONIC ACID
Authors: Raymond G. L. , Wendt I. R. , Kotsanas G. 
Published: June 2007

SUMMARY1. Simultaneous recordings of tension and [Ca2+]i during NANC‐mediated relaxation were made in the rat anococcygeus muscle under various conditions.2. In muscles precontracted with guanethidine, nitrergic stimulations at 2 Hz produced a rapid decrease in both the tension and [Ca2+]i.3. The nitric oxide synthase inhibitor, NG‐nitro‐L‐Arginine (NOLA, 100 μmol/L) completely abolished the decreases in the [Ca2+]i and force response of the NANC‐mediated relaxation.4. Noradrenergic‐mediated contractions elicited by electrical field stimulation were potentiated by the addition of NOLA. In the absence of NOLA, the motor responses were larger in magnitude at 10 Hz stimulation than at 2 Hz. After NOLA, both the force response and the associated rise in [Ca2+]i were substantially increased in comparison to the control stimulations. Proportionately the potentiation of the 2 Hz response was of a far greater magnitude than that of the 10 Hz response.5. The guanylate cyclase inhibitor methylene blue (10 μmol/ L), partially inhibited the force and [Ca2+]i response of the NANC relaxation.6. Following exposure of the muscles to the sarcoplasmic reticulum Ca2+‐ATPase inhibitor, cyclopiazonic acid, (10 μmol/ L) the responses to NANC stimulation were inhibited. The attenuated relaxation response displayed a bi‐phasic timecourse and the Ca2+ change in comparison to that of the control was markedly smaller. In some cases, a relaxation was observed with no detectable change in the [Ca2+]i.7. The results suggest that part of the relaxation response observed with NANC‐mediated relaxation in the rat anococcygeus is dependent on Ca2+ sequestration into the sarcoplasmic reticulum. However, other Ca2+ lowering mechanisms and possible Ca2+ independent mechanisms may also contribute to the NANC relaxation response.
IMPACT OF CYCLO‐OXYGENASE BLOCKADE ON JUXTAMEDULLARY MICROVASCULAR RESPONSES TO ANGIOTENSIN II IN RAT KIDNEY
Authors: Harrison‐Bernard Lisa M. , Carmines Pamela K. 
Published: June 2007

SUMMARY1. Experiments were designed to evaluate the hypothesis that cyclo‐oxygenase products modulate the influence of angiotensin II (AII) on the renal juxtamedullary microvasculature of enalaprilat‐treated rats.2. The in vitro blood‐perfused juxtamedullary nephron technique was utilized to provide access to afferent arterioles, efferent arterioles and descending vasa recta located in the outer stripe of the outer medulla.3. Baseline afferent arteriolar diameter was 20.8 ± 1.9 μm in kidneys subjected to cyclo‐oxygenase blockade (1μmol/L piroxicam), a value significantly lower than that observed in untreated kidneys (26.1 ± 1.0 μm). Baseline diameters of efferent arterioles and outer medullary descending vasa recta did not differ between untreated and piroxicam‐treated groups.4. Topical application of 1 nmol/L AII reduced blood flow through outer medullary descending vasa recta by 22 ± 6% in untreated kidneys and by 24 ± 7% in piroxicam‐treated kidneys.5. In untreated kidneys, AII (0.01–100nmol/L) produced concentration‐dependent afferent and efferent arteriolar constrictor responses of similar magnitudes. Neither afferent nor efferent arteriolar AII responsiveness was significantly altered in piroxicam‐treated kidneys, although afferent responses exceeded efferent responses at AII concentrations ≥ 10 nmol/L.6. We conclude that endogenous cyclo‐oxygenase products exert a vasodilator influence on juxtamedullary afferent arterioles under baseline conditions. Although cyclo‐oxygenase inhibition had little effect on juxtamedullary microvascular responses to AII, the response to high AII concentrations may be modulated by cyclo‐oxygenase products in a manner which delicately alters the relative influence of the peptide on pre‐ vs postglomerular resistances.
EFFECTS OF A SELECTIVE ENDOTHELIN A‐RECEPTOR ANTAGONIST, BQ‐123, IN SALT‐LOADED STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Okada Megumu , Kobayashi Masahiko , Maruyama Hiromi , Takahashi Risa , Ikemoto Fumihiko , Yano Mitsuo , Nishikibe Masaru 
Published: June 2007

SUMMARY1. We examined the effects of a selective endothelin A (ETA)‐receptor antagonist, BQ‐123, on the development of hypertension and organ damage in stroke‐prone spontaneously hypertensive rats (SHRSP) given 1% NaCl for 6 weeks.2. BQ‐123 at doses of 0.7, 2.1 and 7.1 mg/day was continuously administered for 6 weeks to 8 week old salt‐loaded SHRSP, who were given water containing 1% NaCl for the following 6 weeks, via a subcutaneous osmotic minipump.3. Development of high blood pressure was accelerated in salt‐loaded SHRSP compared with that in non‐salt‐loaded SHRSP. After 6 weeks of salt‐loading, incidence of cerebral infarction, renal sclerosis and renal fibrosis were greater in salt‐loaded than non‐salt‐loaded SHRSP.4. BQ‐123 attenuated the age‐related rise in blood pressure in a dose‐dependent manner. The effect coincided with reduction in the incidence of cerebral infarction and prevention of renal sclerosis and fibrosis. Kidney function was improved as observed by an increase in glomerular filtration rate and decreases in urinary protein excretion, blood urea nitrogen and fractional sodium excretion. Furthermore, BQ‐123 prevented increases in the heart weight/bodyweight ratio and aortic wall thickness in salt‐loaded SHRSP.5. These results suggest that endogenous endothelin‐1 (ET‐1) and ETA‐receptors may be, at least in part, involved in the pathogenesis of hypertension and organ damage in salt‐loaded SHRSP.
THE PHYSIOLOGY OF PRE‐ECLAMPSIA
Authors: Brown Mark A. 
Published: June 2007

SUMMARY1. Pre‐eclampsia is a multisystem disorder of human pregnancy with a genetic predisposition. It occurs more commonly in first pregnancies and primarily affects maternal renal, cerebral, hepatic and clotting functions while elevating blood pressure. The foetus is affected through placental insufficiency arising from abnormal ‘placentation’, that is, failure of adequate trophoblast invasion of maternal vasculature, and possibly from abnormal autacoid production.2. Pre‐eclampsia is caused by the placenta; delivery of the placenta is the only known cure. Its manifestations are considered secondary to organ hypoperfusion which arises as a result of vasoconstriction, intravascular coagulation and reduced maternal blood volume.3. Current hypotheses propose that pre‐eclampsia is due to widespread maternal endothelial cell damage, perhaps secondary to a cytotoxic factor released by the placenta. This hypothesis has gained wide acceptance, but scientific evidence is lacking.4. Defining the abnormal balance of vasoactive factors in pre‐eclampsia has proved a difficult task. There is enhanced pressor reactivity to infused angiotensin 11 (AII) despite reduced plasma concentrations of AII, renin and aldosterone. Prostacylclin production appears reduced, and the balance of thromboxane/prostacyclin favours vasoconstriction and platelet aggregation. There is no convincing evidence for enhanced endothelin or reduced nitric oxide production. Plasma concentrations of atrial natriuretic peptide are paradoxically elevated in the face of plasma volume contraction. An intriguing observation, which remains unexplained, is why some vascular beds are affected predominantly in one patient (eg. hepatic ischaemia) while another has a similar degree of hypertension but involvement of a different organ system (eg. renal insufficiency yet normal liver function).5. Volume homeostasis is disturbed with redistribution of intravascular volume to the interstitial fluid space due to increased capillary permeability and in some cases reduced plasma oncotic pressure. This redistribution is not always clinically apparent as peripheral oedema. Whether this change in volume is compensated for by venoconstriction and maintenance of adequate cardiac output is undetermined.6. Improved understanding of the pathophysiology of pre‐eclampsia is necessary to allow better clinical management of this serious disorder.
PEPTIDES AS NEUROTRANSMITTERS IN VASCULAR AUTONOMIC NEURONS
Authors: Morris J. L. 
Published: June 2007

SUMMARY1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co‐localized with non‐peptide transmitters and sometimes with other peptides.2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation (>2–5 Hz) with trains of impulses.3. Neuropeptides can have potent post‐synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature.4. Post‐synaptic effects of neuropeptides tend to be more slowly‐developing and more long‐lasting than those of non‐peptide transmitters.5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non‐peptide transmitters and the slower phases mediated predominantly by one or more neuropeptides.6. Some neuropeptides do not seem to have post‐synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release.7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.
CHANGE IN OPIOID PEPTIDE LEVEL IN THE HEART AND BLOOD PLASMA DURING ACUTE MYOCARDIAL ISCHAEMIA COMPLICATED BY VENTRICULAR FIBRILLATION
Authors: Maslov L. N. , Lishmanov Y. B. 
Published: June 2007

SUMMARY1. The influence of acute myocardial ischaemia (AMI) complicated by ventricular fibrillation (VF) on opioid peptide level in myocardium and blood plasma of rats has been studied.2. Leu‐enkephalin level in myocardium of rats with AMI and VF has been found to be significantly lower than in animals with AMI but without VF.3. Met‐enkephali level has been found to be significantly increased in both animals with VF and without it. We have not found a significant difference in met‐enkephalin level in myocardium of animals with VF and without it.4. AMI was induced to increase the enkephalin and β‐endorphin level in blood plasma of all the animals, whether VF had occurred or not.5. Preliminary administration of D‐Ala2, Leu5, Arg6‐enkephalin, a synthetic analogue of leu‐enkephalin, has prevented a decrease of ventricular fibrillation threshold in experimental coronary occlusion.6. The obtained results allow us to conclude that enkephalins of myocardium but not opioid peptides of blood plasma play an important role in VF occurrence.