bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOLOGICAL PROPERTIES OF THE NATURAL MARINE PRODUCT FUROSPONGIN‐1
Authors: Anderson Andrew P. , Beveridge Andrew A. , Capon Robert 
Published: June 2007

SUMMARY1. The natural marine product, furospongin‐1 (6, 12 and 24.5 μmol/L) significantly inhibited contractions of segments of guinea‐pig ileum induced by submaximal concentrations (0.1 μmol/L) of acetylcholine (ACh) and histamine. Furospongin‐1 (24.5 and 36.7 μmol/L) reduced both the phasic and tonic components of a contraction induced by 30 mmol/L K+ solution in the absence and presence of atropine (1 μmol/L), mepyramine (1 μmol/L) and phentolamine (1 μmol/L). Furospongin‐1 also decreased basal tension and the amplitude of spontaneous phasic contractions of guinea‐pig ileum.2. The mitochondrial ATP synthase inhibitor oligomycin (0.3, 1 and 3 μmol/ L) had a similar concentration‐dependent action, reducing basal activity and contractions evoked by histamine and ACh. Oligomycin also reduced both the phasic and tonic components of a contraction induced by 30 mmol/L K+ solution in the absence and presence of atropine (1 μmol/L), mepyramine (1 μmol/L) and phentolamine (1 μmol/L).3. Furospongin‐l (6 and 37.6 μmol/L) and oligomycin (3 μmol/L) had no effect on contractions of chemically skinned guinea‐pig ileum longitudinal muscle segments. In this same tissue, furospongin‐1 (6, 12 and 24.5 μmol/L) and oligomycin (0.3, 1 and 3 μmol/L) concentration‐dependently reduced tissue levels of ATP.4. In lyzed bovine mitochondria, oligomycin (0.1, 0.3, 1 and 3 μmol/L) inhibited conversion of ATP to ADP whilst furospongin‐1 (6, 12 and 24.5 μmol/L) and carbonyl cyanide m‐chlorophenylhydrazone (0.5 mmol/L) had no significant effect on ATP breakdown.5. Furospongin‐1 (12 and 24.5 μmol/L) and oligomycin (3 μmol/L) had no effect on State 4 mitochondrial respiration of whole bovine mitochondria, but converted State 3 back to State 4 respiration. Carbonyl cyanide m‐chlorophenyl‐hydrazone (0.5 mmol/L) increased oxygen consumption in both situations.6. These results suggest that furospongin‐1 may inhibit the activity of inner mitochondrial membrane ADP‐ATP translocases or other membrane transporters to inhibit ATP synthesis.
THE DIFFERENCE IN NIFEDIPINE SENSITIVITY BETWEEN HYPERTENSIVE AND NORMOTENSIVE RAT AORTAE IS DEPENDENT ON AGE
Authors: Jiang Guang‐Chi , Iwanov Victor , Moulds Robert F. W. 
Published: June 2007

SUMMARY1. In order to investigate further whether the increased sensitivity to inhibition by nifedipine of the responses to nor‐adrenaline of aortae from spontaneously hypertensive stroke‐prone (SHRSP) rats is related to the development of the hypertension, we have compared the sensitivity to noradren‐aline, potassium chloride (KCl) and nifedipine of aortae from SHRSP and control (Wistar‐Kyoto) WKY rats of different age groups (young: 3–5 weeks, and adult: 13–16 weeks).2. The sensitivity to KCl was found to be less in the aortae from the adult WKY group than in any of the other three groups. Responses to noradrenaline of the adult WKY aortae were also less sensitive to inhibition by nifedipine in comparison to each of the other three groups.3. The changes in sensitivity were not due to the changes in the populations of α1‐adrenoceptor subtypes as responses of the adult SHRSP aortae to noradrenaline were more sensitive to nifedipine in the presence of either the α1‐adrenoceptor subtype antagonists chloroethylclonidine or WB 4101 than were those of the adult WKY aortae, but aortae from the young SHRSP were not.4. These results suggest that, rather than the SHRSP aorta becoming more sensitive to nifedipine and potassium depolarization as hypertension develops, it is the WKY aorta that becomes more resistant as it matures.
MOLECULAR BIOLOGY AND BIOCHEMISTRY OF NATRIURETIC PEPTIDE FAMILY
Authors: Ogawa Yoshihiro , Itoh Hiroshi , Nakao Kazuwa 
Published: June 2007

SUMMARYThe natriuretic peptide family consists of three endogenous ligands; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C‐type natriuretic peptide (CNP), and is involved in the regulation of cardiovascular homeostasis. Both ANP and BNP act mainly as cardiac hormones and are produced predominantly by the atrium and ventricle, respectively. Expression of the BNP and ANP genes is greatly augmented in patients with congestive heart failure and animal models of ventricular hypertrophy or cardiomyopathy. In the heart, the BNP gene expression is regulated differently from the ANP gene expression both at transcriptional and post‐transcriptional levels. Transgenic technology has provided the direct evidence that BNP as well as ANP is involved in the chronic blood pressure control. Contrasting with ANP and BNP, CNP does not act as a cardiac hormone but as a neuropeptide or an endothelium‐derived autocrine/paracrine regulator. Endothelial production of CNP is remarkably augmented by various cytokines and growth factors such as transforming growth factor‐β and tumour necrosis factor‐α, suggesting the pathophysiological significance of CNP in the process of various vascular disorders. Chromosomal mapping of natriuretic peptides has revealed that the CNP gene is localized on mouse chromosome 1, while ANP and BNP are tightly linked on mouse chromosome 4, suggesting that CNP, a local regulator, is functionally and evolutionarily distinct from ANP and BNP, both of which are cardiac hormones. Understanding the molecular biology and biochemistry of the natriuretic peptide family will lead to the better understanding of its physiological and pathophysiological implication, and the clinical application in cardiorenal regulation.
CARDIOVASCULAR ACTIONS OF INSULIN: ARE THEY IMPORTANT IN LONG‐TERM BLOOD PRESSURE REGULATION?
Authors: Hall John E. , Brands Michael W. , Zappe Dion H. , Alonso‐Galicia Magdalena 
Published: June 2007

SUMMARY1. In recent years, there has been considerable interest in the possibility that insulin may have important cardiovascular as well as metabolic actions. Perhaps the best documented cardiovascular effect of insulin is to cause peripheral vasodilation, especially in skeletal muscle. Hyperinsulinaemia also stimulates sympathetic activity and causes antinatriuresis, but these effects may be linked, at least in part, to the metabolic actions of insulin that elicit peripheral vasodilation and a tendency toward hypotension. Normal, fasting levels of insulin appear to have very little influence on peripheral vascular resistance, sympathetic activity or renal sodium excretion.2. Decreased sensitivity of the peripheral tissues to the metabolic effects of insulin and compensatory hyperinsulinaemia have been postulated to play key roles in the pathophysiology of diseases such as hypertension and atherosclerosis. Although impaired insulin action (insulin resistance) and hyperinsulinaemia often accompany essential hypertension, especially when associated with obesity, there is currently little direct evidence for a cause and effect relationship between insulin resistance, hyperinsulinaemia and increased arterial pressure. Chronic increases in plasma insulin levels in dogs and humans have not been shown to cause hypertension, although hyperinsulinaemia raises blood pressure in rats.3. Further research is needed to determine whether there are pathophysiological conditions or genetic factors that may predispose humans to a hypertensive effect of hyperinsulinaemia and/or insulin resistance.
ELECTROPHYSIOLOGICAL PROPERTIES OF THE RAT MIDDLE CEREBRAL ARTERY AT DIFFERENT LEVELS OF PASSIVE WALL TENSION
Authors: McPherson Grant A. , Keily Simon G. 
Published: June 2007

SUMMARY1. Simultaneous measurements of intracellular membrane potential and myogenic tone of proximal segments of the rat middle cerebral artery, mounted in a small vessel myograph, were made at two levels of passive wall tension.2. At low levels of passive tension (less than 0.25mN/mm) vessels had a resting membrane potential of approximately ‐65mV. Addition of KCl (5–60 mmol/L), BaCl2 (0.01–3 mmol/L) or tetraethylammonium (TEA; 0.1–3 mmol/L) resulted in a concentration‐dependent depolarization, to approximately—40 mV, generally associated with a contractile response. After the application of high levels of passive tension (to approximately 2mN/mm maximum) the resting membrane potential of the smooth muscle cells was—40 to—45 mV. This more positive membrane potential was generally associated with an increase in myogenic tone of the vessel. Under these conditions, addition of 5–20 mmol/L KCl resulted in a strong hyperpolarization of the cell along with a concomitant decrease in myogenic tone of the artery. The hyperpolarization and vasorelaxation induced by KCl (5–20 mmol/L) were blocked by BaCl2 (0.5–1 mmol/L).3. While the addition of ryanodine (10 μmol/L) to vessels under low tension had no effect, when added to a vessel under high tension, this agent caused a rhythmic oscillation in membrane potential. This oscillation was augmented by BaCl2 (1mmol/L) and inhibited by nifedipine (10nmol/L) and 4‐aminopyridine (1 mmol/L).4. This study suggests that the electrophysiological and mechanical properties of the isolated rat middle cerebral artery depend on the passive resting conditions under which the vessel is studied. The depolarization of membrane potential observed with increased passive tension appears to result from the closure of an inward rectifying K+ channel. These results indicate that the inward rectifying K+ channel plays an important role in regulating vascular reactivity due to its functional dependence on the mechanical status of the blood vessel.
EFFECTS OF DIETARY FIBRE ON DIMETHYLHYDRAZINE‐INDUCED CHANGES IN PROSTANOID CONCENTRATIONS IN RAT COLONIC MUCOSA
Authors: Kanamori Shin‐ichi , Sugiyama Satoru , Goto Hidemi , Hayakawa Tetsuo , Shimomura Yoshiharu , Ozawa Takayuki 
Published: June 2007

SUMMARY1. This study was designed to elucidate the effects of guar gum, a dietary fibre, on changes in prostanoid contents induced by 1,2‐dimethylhydrazine, a carcinogenic agent, in rat colonic mucosa.2. Prostanoid contents were determined using high performance liquid chromatography; five prostanoids, namely 6‐keto‐prostaglandin F1α, prostaglandin F2α, prostaglandin E2, prostaglandin D2 and thromboxane B2, were detected.3. Four subcutaneous injections of dimethylhydrazine, 60 mg/kg every 6 days, increased the mucosal concentrations of prostaglandin E2 and thromboxane B2 by approximately 50%. Other prostanoids did not change significantly throughout the experiments.4. In rats treated with dimethylhydrazine and a fibre diet a significant increase in thromboxane B2 content was not observed, although a significant increase in prostaglandin E2 content was observed. These effects were observed in rats fed with fibre diet over 20 days but not observed in rats fed with fibre diet over 10 days.5. From these results and the report that aspirin use at low doses is effective in the reduction of the risk of fatal colonic cancer, inhibiting thromboxane B2 synthesis by fibre diet might he involved in the protective effect against the occurrence of colonic cancer.
EFFECTS OF ENDOTHELIN‐1 ON THE CONTRACTILITY OF CARDIOMYOCYTES FROM THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Delbridge Leanne M. , Morgan Trefor O. , Harris Peter J. 
Published: June 2007

SUMMARY1. Disturbances in cardiovascular responsiveness to endogenous endothelin‐1 (ET‐1) may play a significant role in the pathogenesis of essential hypertension. In this study the inotropic responses of cardiomyocytes derived from normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rat (SHR) strains to ET‐1 (10‐11‐10‐8 mol/L) were characterized. Isotonic contraction cycles of ventricular cardiomyocytes isolated from age‐matched (11 week) WKY and SHR rats were recorded using a rapid digital imaging technique and evaluated by computation of a range of normalized parameters.2. The maximum effect of ET‐1, eliciting a 60–70% increase in myocyte shortening after 3 min, was observed at 10‐9 mol/L in both strains, and was associated with elevations in the rate of shortening and lengthening, abbreviated latency, contractile cycle prolongation and delayed time to peak shortening.3. No evidence for a significant strain dependent difference in the relative responsiveness to ET‐1 was detected. This finding indicates that altered sensitivity to ET‐1 is unlikely to be a major factor underlying the development of hypertension in this model.4. The distinct nature of the alterations in contractile parameters produced by ET‐1 compared with angiotensin II (AII) suggests that the prevailing cellular mechanisms of action of these peptides are different and that ET‐1 is not a paracrine or autocrine inotropic intermediate for AII
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA
Authors: Cameron D. L. , Williams J. T. 
Published: June 2007

SUMMARY1. Dopamine D1 and SHT1d receptors are found on the terminals of afferent GABA neurons that synapse on the ventral tegmental area (VTA) dopamine neurons. The role of these receptors in the actions of cocaine was investigated using intracellular recordings in a brain slice preparation. Synaptic potentials were generated in the slice and GABA‐mediated inhibitory post‐synaptic potentials (IPSP) were identified.2. Stimulation of dopamine D1 receptors selectively enhanced the GABAb IPSP, and this effect was blocked by D1 antagonists. The magnitude of the IPSP was decreased when D1 antagonists were applied in isolation, suggesting tonic D1 receptor stimulation via dendritically released dopamine.3. Cocaine had an opposite effect and selectively decreased the magnitude of the GABAb IPSP. This action was mimicked by 5HT and the SHT1d agonist sumatriptan, and attenuated by the 5HTI1D/2c antagonist, metergoline. The action of cocaine was also mimicked by the 5HT‐releasing agent, fenfluramine, and blocked by pre‐incubation of the slice with the 5HT‐depleting agent, para‐chloroamphetamine.4. The results of this study suggest that dopamine and 5HT have opposing roles in modulating GABA input into VTA dopamine neurons. The actions of cocaine on this interplay may have implications for understanding its addictive properties.
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: FREE RADICAL TOXICOLOGY AND ANTIOXIDANT DEFENCE
Authors: Winterbourn Christine C. 
Published: June 2007

SUMMARY1. A large number of compounds that have toxic effects can be metabolized to free radicals and secondary reactive oxygen species. These may be directly damaging or may affect cell function by altering regulatory mechanisms through changing redox status.2. Protection is provided by an integrated system of anti‐oxidant defences. This includes reduced glutathione, one of the functions of which is to scavenge free radicals. It acts by channelling radicals to superoxide so that the one enzyme, superoxide dismutase, has a major control over radical reactions in the cell.
CHANGES IN INTRA‐ AND EXTRACRANIAL TISSUE BLOOD FLOW UPON STIMULATION OF A RETICULAR AREA DORSAL TO THE FACIAL NUCLEUS IN CATS
Authors: Kuo Jon‐Son , Chyi Theresa , Yang May C. M. , Chai Chok‐Yung 
Published: June 2007

SUMMARY1. A small area in the dorsal part of the lateral tegmental field specifically responsible for the increase of blood flow in the common carotid artery (CCA) without accompanying change in the resting blood pressure was first identified in our laboratory. Since the area is located just dorsal to the facial nucleus, we named it the dorsal facial area (DFA; Kuo et al. 1987).2. The purpose of this study was to clarify whether an increase of blood flow in intra‐ and/or extracranial tissues was responsible for the increase in CCA blood flow upon DFA stimulation, and to determine the role of cholinergic transmission in this response.3. In 20 cats under chloralose and urethane anaesthesia, microsphere reference flow technique was used to measure the regional blood flow of intra‐ and extracranial tissues.4. Electrical stimulation of the DFA appeared to increase the regional blood flow of both cerebral hemispheres (intra‐cranial tissues) and to increase predominantly the regional blood flow of extracranial tissues on the side ipsilateral to stimulation. Increases in the regional blood flow of intracranial tissues were enhanced after i.v. administration of atropine but reduced with physostigmine. In contrast, increases in the regional blood flow of extracranial tissues were reduced after i.v. atropine but enhanced after physostigmine.5. These findings suggest that DFA stimulation may promote the release of ACh in intra‐ and extracranial vessels. The muscarinic action may restrict the DFA‐induced increase in blood flow of intracranial tissues, but enhance that of extracranial tissues.
ATRIAL NATRIURETIC PEPTIDE FRAGMENTS IN DOGS WITH EXPERIMENTAL HEART FAILURE
Authors: Habibullah Ahmed A. , Villarreal Daniel , Freeman Ronald H. , Dietz John R. , Vesley David L. , Simmons John C. 
Published: June 2007

SUMMARY1. This study in the canine arteriovenous (AV) fistula model of high‐output heart failure (HOHF) evaluated the chronic temporal changes in plasma ANF and pro ANF 31–67 and their relationship to body‐fluid balance and the renin‐aldosterone axis. In addition, the haemodynamic, hormonal and renal excretory effects of synthetic pro ANF 31–67 infusions were examined in normal and AV fistula dogs with compensated HOHF.2. Following the construction of the AV fistula, the dogs exhibited chronic parallel elevations in right atrial pressure and the plasma concentrations of ANF and pro ANF 31–67. The gradual increases in the two peptides were associated with a gradual decrease in plasma renin activity and the re‐establishment of sodium balance.3. In normal and compensated AV fistula dogs, synthetic pro ANF 31–67 produced similar significant reductions in arterial blood pressure, right atrial pressure and elevations in urinary sodium excretion. These effects were not associated with increases in plasma or urinary cyclic GMP (cGMP).4. These results suggest that the elevation in the endogenous circulating levels of pro ANF 31–67 in the AV fistula dogs may represent one chronic adaptive mechanism to achieve body fluid homeostasis. Furthermore, via potentially different mechanisms of action, ANF and pro ANF 31–67 may coordinate and contribute to the regulation of haemodynamic and renal function during physiological and pathophysiological situations.
CONTROL OF INTRAVASCULAR VOLUME DURING PREGNANCY
Authors: Kaufman Susan 
Published: June 2007

SUMMARY1. We wished to determine whether, during pregnancy, there is reduced renal response to atrial distension, whether secretion of atrial natriuretic factor (ANF) is suppressed and whether neural input from the atrial volume receptors to the central nervous system is altered.2. Conscious, chronically instrumented female rats were used. Atrial distension was achieved by implanting small balloons positioned at the superior vena caval/right atrial junction; inflation of the balloon did not impede blood flow through the heart.3. In virgin rats, atrial stretch caused increased urine volume, urine sodium and potassium output and decreased free water clearance. These responses were abolished during pregnancy.4. In response to atrial stretch, plasma ANF levels increased significantly in virgin rats. No such secretory response was observed in the pregnant animals.5. Distension of isolated atria derived from unmated and 7 day pregnant rats resulted in an increase in secretion of ANF into the perfusate. Atria from 14 and 21 day pregnant rats were unresponsive to distension.6. Pretreatment with oestradiol (50 μg daily for 10 days) caused plasma ANF levels and ANF secretion by isolated perfused atria to increase. By contrast, testosterone pretreatment (15 mg twice weekly for 2 weeks) abolished stretch induced secretion of ANF by isolated atria.7. C‐fos activity in the paraventricular nucleus of virgin rats increased in response to atrial distension. This response was reduced in the 7 day pregnant rats and abolished at 21 days.8. We conclude that there is attenuation of both hormonal and neural responses to atrial distension in the pregnant animal. This allows blood volume to increase without eliciting homeostatic mechanisms to eliminate the extra fluid.
ALCOHOL, HYPERTENSION, CORONARY DISEASE AND STROKE
Authors: Lip Gregory Y. H. , Beevers D. Gareth 
Published: June 2007

SUMMARY1. The association between alcohol and hypertension has been recognized for several years.2. However, it remains a paradox that if alcohol does cause hypertension there is little convincing evidence that alcohol is related to the cardiovascular complications of hypertension such as strokes and heart attacks. The relationship between alcohol and strokes remains inconclusive and there is evidence that moderate alcohol consumption may be protective against heart attacks.3. It is possible, therefore, that alcohol does not so much cause hypertension, but rather a rapidly reversible rise in blood pressure which does not cause cardiovascular damage. When managing hypertensive patients, however, relevant counselling can bring about a useful fall in blood pressure.
CAN WE RECOMMEND FISH OIL FOR HYPERTENSION?
Authors: Howe Peter R. C. 
Published: June 2007

SUMMARY1. The ability of the n‐3 fatty acids in fish oil to lower blood pressure has been established. Dietary fish oil supplementation is effective in mild hypertension and, in certain cases, as an adjunct therapy in drug‐treated hypertension. Efficacy may be enhanced by restricting sodium intake.2. The overall benefit of fish oil in hypertension, however, has not yet been fully evaluated. We still need further information on the relative efficacy of individual omega‐3 fatty acids and on additional cardiovascular benefits and possible disadvantages of increasing their consumption.
RECENT INSIGHTS INTO DIETARY FATS AND CARDIOVASCULAR DISEASE
Authors: Dimmitt Simon B. 
Published: June 2007

SUMMARY1. Fat deposition in the arterial intima is fundamental to the atheroma process. Circulating lipoproteins are thought to be the source of much of the deposited fat. The interplay of dietary fat has not been fully clarified.2. Observational studies have furnished evidence of relationships between the different dietary fats and clinical cardiovascular events. In these, total fat and in particular, saturated fat appear culprit. Mono‐unsaturated (MUFA) and polyunsaturated (PUFA) fats have less consistent relationships with cardiovascular disease, though all classes of fatty acid are found in atheroma.3. Comparing the effects on lipoproteins of saturates, mono‐unsaturates and polyunsaturates, they all increase high density lipoproteins (HDL) and reduce triglycerides when substituted isocalorically for carbohydrate. Saturates increase low density lipoproteins (LDL), while PUFA > MIJFA reduce LDL.4. Upon oxidative modification, lipoproteins are more liable to arterial deposition and, in vitro at least, LDL oxidizability is enhanced by enrichment with PUFA.5. Trans‐MUFA have some unique properties in that they somewhat resemble saturates and seem to predispose to coronary disease, quite possibly because of their adverse effects on LDL, HDL and Lp(a) levels.6. ω‐3 fatty acids seem unique among the dietary fats in that they inhibit thrombosis and platelet aggregation, and can lower blood pressure.7. The net effect of these various potential influences of fatty acids on atherogenesis in vivo is unclear. It may well be that all fats, with the exception of the ω‐3 class, are detrimental with respect to atherogenesis. Modification of the diet, with particular attention to fat, has been demonstrated to reduce clinical coronary events in several studies. Restriction of all fats, save for that in fish, preferably along with weight reduction, appears desirable in order to effectively reduce cardiovascular disease risk.