bluuebunny/crossref_metadata_2025_split huggingface dataset:
VASCULAR ENDOTHELIN RESPONSIVENESS AND RECEPTOR CHARACTERISTICS IN VITRO AND EFFECTS OF ENDOTHELIN RECEPTOR BLOCKADE IN VIVO IN CYCLOSPORIN HYPERTENSION
Authors: Phillips P. A. , Rolls K. A. , Burrell L. M. , Casley D. , Aldred K. L. , Hardy K. J. 
Published: June 2007

SUMMARY1. The aim of these studies was to determine the role of endothelin in cyclosporin A ([CsA], 10 mg/kg per day, s.c., for 30 days) hypertension in the rat.2. There were no significant differences in plasma endothelin concentrations, in vitro mesenteric vascular membrane [125I]‐endothelin‐l (ET‐1) binding characteristics or myographic vascular responses to endothelin‐1 between the CsA and control groups (systolic blood pressure 135 ± 1 vs 127 ± 1 mmHg, respectively, P<0.001).3. Twenty‐four hours after selective endothelin type A receptor blockade in vivo with BQ123, blood pressure in CsA hypertensive rats was lowered to levels of normotensive controls.4. These results suggest that changes in endothelin synthesis rather than changes in vascular sensitivity and/or ET‐1 receptor characteristics may contribute to CsA‐induced hypertension.
SUPPRESSION OF NITRIC OXIDE PRODUCTION BY CYCLOSPORIN A AND FK506A IN RAT VASCULAR SMOOTH MUSCLE CELLS
Authors: Akita K. , Dusting G. J. , Hickey H. 
Published: June 2007

SUMMARY1. The effects of the immunosuppressants cyclosporin A (CsA) and FK506 on nitric oxide (NO) synthesis induced by lipopolysaccharide (LPS) or cytokines were examined in rat vascular smooth muscle cells (VSMC) in culture.2. CsA inhibited by up to 90% the accumulation of nitrite induced by LPS, but FK506 had a weaker effect on nitrite accumulation induced by LPS in these cells. Both CsA and FK506 (at 1 μmol/L) significantly inhibited nitrite production induced by recombinant murine interleukin‐1β (rIL‐1β).3. Given their differing potency, it is likely that CsA and FK506 suppress induction of NO synthase through different intracellular mechanisms. This action could contribute to the side effects of CsA therapy.
GLYCEROL DEHYDRATES OEDEMATOUS AS WELL AS NORMAL BRAIN IN DOGS
Authors: Wang Jia‐Yi , Chen Jiann‐Liang 
Published: June 2007

SUMMARY1. Although the effect of glycerol on reducing intracranial pressure has been widely investigated, only a few studies have reported its dehydrating effect on brain oedema caused by infarction, ischaemia, microembolism and cold injury, but none on traumatic oedema. In this study the effects of glycerol (1 g/kg, i.v. bolus infusion at a rate of 0.04 g/kg per min) on traumatic and cryogenic cerebral oedema and on normal brain were compared in the anaesthetized dog. The tissue water content was measured with the gravimetric method.2. Oedema resulting from mechanical trauma was initiated 4 h prior to treatment with glycerol (8 dogs) or vehicle (5 dogs) by closed head contusion with fixed force under general anaesthesia. Tissue samples underneath the region of contusion were taken, before and 1 h after infusion of glycerol or vehicle, for the measurement of water content.3. Glycerol infusion decreased the water content in white matter of the traumatic brain model from 76.54 ± 1.70% to 70.73 ± 1.54% (P<0.001). In normal brain the reduction was from 68.42 ± 0.48% to 65.36 ± 0.39% (P<0.001). Neither vehicle nor glycerol infusion resulted in significant changes in specific gravity of the gray matter.4. Cryogenic oedema was initiated 3 h prior to the infusion of glycerol or vehicle by applying unilaterally a brass conical cup (bottom diameter 1 cm) filled with dry ice‐acetone (‐ 65°C) to the exposed dura for 1 min. The contralateral hemisphere, which was not subjected to cold injury, was used for determination of water content of normal gray and white matter.5. Glycerol infusion decreased the water content in the white matter of the cold‐injured region from 75.38 ± 0.69% to 72.57 ± 0.58% (P<0.001). In the normal white matter the reduction was from 68.63 ± 0.34% to 65.48 ± 0.49% (P<0.001).6. Our data indicate that glycerol decreases water content of the white matter in traumatic and cold‐injured oedematous brain as well as in normal brain.
INHIBITION BY ETHACRYNIC ACID OF NO‐MEDIATED RELAXATIONS OF THE RAT ANOCOCCYGEUS MUSCLE
Authors: Li C. G. , Brosch S. F. , Rand M. J. 
Published: June 2007

SUMMARY1. The effects of ethacrynic acid were studied on relaxations elicited by nitric oxide (NO), the NO‐donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), nitrergic nerve stimulation and the NO‐independent agent papaverine in isolated preparations of rat anococcygeus muscles.2. Ethacrynic acid (100 μmol/L) produced complete relaxation of partially contracted anococcygeus muscles, but the tone recovered after the ethacrynic acid was washed out. Following exposure to ethacrynic acid, the relaxant responses to NO, SNP, GTN and nitrergic nerve stimulation were abolished or markedly reduced; however, the response to papaverine was only slightly reduced.3. The presence of 3 mmol/L l‐cysteine during the period of exposure to ethacrynic acid prevented the inhibition of the relaxing effects of SNP, GTN and nitrergic nerve stimulation almost completely, but did not affect the slight reduction in responses to papaverine.4. The addition of l‐cysteine (3 mmol/L) after incubation with ethacrynic acid did not significantly affect the inhibited responses to SNP and GTN; however, the inhibited responses to nitrergic nerve stimulation were slightly but significantly increased.5. The results suggest that endogenous sulphydryl groups are required for the actions of NO, NO‐donating drugs and the nitrergic transmitter in the rat anococcygeus muscle and possibly for the synthesis or release of the nitrergic transmitter.
INTERACTIONS BETWEEN THE CIRCULATORY EFFECTS OF CENTRAL HYPOVOLAEMIA AND ARTERIAL HYPOXIA IN CONSCIOUS RABBITS
Authors: Blake Duncan W. , Evans Roger G. , Ludbrook John , Petring Oscar U. 
Published: June 2007

SUMMARY1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval‐cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min.2. Caval‐cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O2, with and without the addition of 3–4% CO2, in randomized order.3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased.4. During Phase I, there were independent linear relationships between Pao2 (but not Pao2) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao2, the greater was the rate of fall of SVCI and the less the rate of fall of MAP.5. There was an inverted U‐shaped effect of Pao2, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O2), Phase II occurred later than during normoxia (21% O2); and (b) across the normoxic and hypoxic gas mixtures (21–8% O2, with and without added CO2), there was an independent linear relationship between Pao2 (but not Pao2 or Pao2×Pao2) and the level of CI at which Phase II occurred. That is, the lower the level of Pao2, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.
CILIARY BEAT FREQUENCY AT SIX LEVELS OF THE RABBIT AND RAT RESPIRATORY TRACT IN COW, DOG, GUINEA‐PIG, PIG
Authors: Joki Susanna , Saano Veijo 
Published: June 2007

SUMMARY1. The ciliary beat frequency (CBF) of six animal species from six regions of the respiratory tract were measured: inferior turbinate, nasopharynx, the upper part of trachea from first to second cartilage, the lower part of trachea, main bronchus and subsegmental bronchi. Cow, pig, dog, rabbit, guinea‐pig and rat were studied.2. There were no significant differences in the CBF values between cow, pig and dog, and the ciliary activity was essentially the same (11.3‐16.9 Hz) in all parts of the respiratory tract.3. In the rat, the CBF was slower, especially in subsegmental bronchi (6.8 Hz).4. In general, CBF was higher in upper than lower airways, with the exception of guinea‐pig.5. Signal quality was the highest in guinea‐pig tissue, whereas rat tissue produced the signal with the widest variation in CBF and the highest proportion of distorted waveforms.6. Therefore, for studying drug effects on ciliary activity, guinea‐pig seems to be a more suitable animal than the more commonly used rabbit or rat. In drug comparisons, the same part of the respiratory tract and the same animal species should be used.
LOCAL NEURAL CONTROL OF INTESTINAL MOTILITY: NERVE CIRCUITS DEDUCED FOR THE GUINEA‐PIG SMALL INTESTINE
Authors: Bornstein J. C. 
Published: June 2007

SUMMARY1. Propulsion of digesta along the intestine appears to occur by the action of a series of local reflexes which cause contraction oral to the digesta and relaxation of circular muscle on the anal side.2. There is now substantial evidence available about the identities of the enteric neurons that mediate these reflexes.3. The motor neurons and interneurons of the reflex pathways lie within the myenteric plexus. These neurons can be classified electrophysiologically as S‐neurons and have distinctive projections and neurochemistries.4. The sensory neurons may lie in the myenteric plexus, but there is some evidence for sensory neurons in the submucous plexus. A contribution from extrinsic sensory neurons to local motility reflexes cannot be ruled out. Intrinsic sensory neurons are probably AH‐neurons and are large multi‐axonal cells.
ALINIDINE PREVENTS HYPOPERFUSION‐INDUCED TRANSMURAL FLOW REDISTRIBUTION IN ISOLATED PACED RAT HEARTS
Authors: Weihs H. , Mutschled E. , Walland A. 
Published: June 2007

SUMMARY1. The effect of alinidine on transmural flow redistribution during hypoperfusion was studied in the isolated rat heart.2. Low flow perfusion of paced (5 Hz) rat Langendorff preparations with Tyrode's solution for 60 min resulted in loss of left ventricular pressure amplitude and contracture.3. In the presence of 45.6 μmol/L alinidine in the hypoperfusion medium contractility was maintained and contracture was missing.4. Myocardial sphere densities were assessed by infusion of fluorescent microspheres after 60 min of hypoperfusion. Histomorphometric evaluation of the left ventricular wall indicated marked redistribution of myocardial flow to the epicardium. Endolepicardial quotients of sphere densities were significantly greater in alinidine‐treated hearts.5. Perfusion of hearts with 45.6 μmol/L alinidine for 30 min at a pressure of 80 cmH2O decreased coronary flow and contractility, but did not change the transmural quotient of sphere densities.6. These results show that in isolated rat hearts with a ventricular wall of only 3–4 mm thickness severe hypoperfusion induces a shift in transmural flow distribution which is prevented by alinidine.
ANTI‐OBESITY AND ANTI‐DIABETIC EFFECTS OF CARTEOLOL IN NON‐INSULIN‐DEPENDENT DIABETIC MICE
Authors: Takahashi Hakuo , Nakano Koji , Yasuda Tomoko , Komiyama Yutaka , Murakami Takashi , Nishimura Masato , Nakanishi Tadashi , Sakamoto Masanori , Nanbu Akira , Yoshimura Manabu 
Published: June 2007

SUMMARY1. When carteolol, a β‐adrenergic blocker, was administered to KK‐Ay/Ta Jcl mice that are obese and develop spontaneously non‐insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK‐Ay/Ta Jcl mice, abolition of the weight gain might be attributed to increased energy metabolism.2. Non‐fasting serum glucose levels in carteolol‐treated mice at the age of 17 weeks were within normal range (118±4 vs 186±12 mg/dL). An intraperitoneal glucose‐tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88±6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8±0.8 vs 33.3 ± 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361±44 vs 541 ±32 mg/dL) were significantly lower in carteolol‐treated mice than those in the control group at the age of 20 weeks.3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity.4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT, When the regional blood flow was measured by radioactive microspheres in rats, blood flow in BAT and white adipose tissue was markedly increased by carteolol.5. These findings indicate that carteolol blocks β1‐ and β2‐adrenoceptors, but may stimulate β‐receptors particularly in the adipose tissue to promote lipolysis and thermogenesis, and to consume excess energy in mice. Thus, carteolol does not influence mouse growth, but may prevent obesity leading to increases in insulin sensitivity.
POSSIBLE MECHANISMS INVOLVED IN THE NATRIURETIC RESPONSE TO ATRIAL NATRIURETIC FACTOR (ANF) AND PROANF 31–67 IN THE RAT
Authors: Dietz John R. , Vesely David L. , Nazian Stanley J. 
Published: June 2007

SUMMARY1. The present study was conducted to compare the mechanisms involved in the natriuretic response to atrial natriuretic factor (ANF) and pro ANF 31–67. The peptides were infused intravenously into anaesthetized rats at 10 pmol/min for 40 min.2. Only ANF produced a significant decrease in arterial pressure; the maximum decrease was 11 mmHg (P<0.05).3. Both peptides produced significant increases in sodium excretion (P<0.05) but only ANF increased the cyclic GMP (cGMP) excretion rate (P<0.01) and neither peptide had a significant effect on plasma renin activity or glomerular filtration rate (GFR). Pro ANF 31–67 did not increase the plasma levels of ANF.4. These results demonstrate that both ANF and proANF 31–67 have natriuretic effects via a tubular mechanism and suggest that the natriuretic effects of ANF are mediated by cGMP while the effects of pro ANF 31–67 are mediated by a different mechanism, not involving changes in cGMP excretion, changes in GFR or a reduction in renin secretion.
DEXTROSE‐, ADENOSINE‐ AND MAGNESIUM‐INDUCED PROTECTIVE ACTIONS DURING ANOXIA AND REPERFUSION IN CANINE PURKINJE TISSUE
Authors: Bhattacharyya M. L. , Sarker S. , Seth K. 
Published: June 2007

SUMMARY1. The effects of dextrose, magnesium (Mg) and adenosine on membrane potential and force of contraction were studied in driven and overdriven canine cardiac Purkinje tissue.2. Dextrose (50 mmol/L) and adenosine (4–6 mmol/L) both showed protective action (the latter to a lesser extent) against simulated anoxia and reperfusion‐ induced arrhythmias, increased force of contraction transiently on reperfusion, and the former sustained the increase in force to a lower level as long as it was in the superfusing solution.3. Dextrose (50 mmol/L) and Mg (5 mmol/L) restored overdrive‐ induced hyperpolarization during simulated anoxia. Adenosine was largely ineffective.4. It was concluded that dextrose and adenosine (to a lesser extent) protect against arrhythmias by replenishing the critical intracellular pool of ATP which controls membrane transport of electrolytes such as K and Ca. Restoration of Na‐K ATPase activity alone (as in the case of high Mg concentrations) is not sufficient to prevent arrhythmias.
CHARACTERIZATION OF BINDING SITES FOR [3H]‐IDAZOXAN, [3H]‐P‐AMINOCLONIDINE AND [3H]‐RAUWOLSCINE IN THE KIDNEY OF THE DOG
Authors: Evans Roger G. , Haynes John M. 
Published: June 2007

SUMMARY1. We characterized the binding of [3H]‐rauwolscine, [3H]‐p‐aminoclonidine and [3H]‐idazoxan in a dog kidney membrane preparation. Our aim was to determine the pharmacological nature of the α2‐adrenoceptor‐ and imidazoline‐preferring binding sites in this organ.2. [3H]‐Rauwolscine bound to an apparent single site with an affinity (KD) of 2.2 nmol/ L and a maximum density (Bmax) of 58.5 fmol/mg protein, when 10 μmol/L idazoxan defined non‐specific binding. However displacement studies demonstrated that a number of compounds, including prazosin, inhibited [3H]‐rauwolscine binding in a complex manner consistent with displacement from two distinct binding sites. The majority (69%) of the [3H]‐rauwolscine binding sites had a relatively low affinity for prazosin (KI= 398 nmol/L), while the remainder had a relatively high affinity for prazosin (KI= 7.9 nmol/ L).3. [3H]‐p‐Aminoclonidine bound to an apparent single site (KD= 5.2 nmol/L; Bmax= 72.4 fmol/mg protein), when 10 μmol/L phentolamine defined non‐specific binding. When 1 μmol/L of the potent and selective α2‐adrenoceptor antagonist 2‐methoxyidazoxan was included in the incubate, no specific binding was detected. We therefore conclude that under the conditions of this experiment [3H]‐p‐aminoclonidine binds only to α2‐adrenoceptors in the dog kidney.4. [3H]‐Idazoxan bound to two sites, with a higher (KD= 0.95 nmol/L; Bmax= 43.9 fmol/mg protein) and lower (KD= 9.1 nmol/L; Bmax= 93.8 fmol/mg protein) affinity, respectively, when 1 mmol/L phentolamine defined non‐specific binding. When 10 μmol/ L GTPγS was included in the incubate, the low affinity site was unaffected but the maximum binding at the higher affinity site was reduced by 79%. 2‐Methoxyidazoxan displaced [3H]‐idazoxan in a monophasic manner and with low potency (IG50=11.5 μmol/L). Yohimbine, efaroxan, clonidine, rilmenidine, guanabenz and idazoxan itself displaced [3H]‐idazoxan in a complex manner; the slope of the displacement curves being less than unity.5. We conclude that the dog kidney contains a heterogeneous population of α2‐adrenoceptors that can be labelled either with [3H]‐rauwolscine or [3H]‐p‐aminoclonidine. The dog kidney also contains a heterogeneous population of non‐adrenoceptor imidazoline‐preferring binding sites of the I2‐subtype, that can be labelled with [3H]‐idazoxan. The binding site for which [3H]‐idazoxan has the highest affinity appears to be coupled to a guanine nucleotide binding regulatory protein.
CLEARANCE OF CHYLOMICRON‐LIKE LIPID EMULSIONS IS INCREASED IN NORMAL RABBITS BUT NOT IN HETEROZYGOUS WATANABE HERITABLE HYPERLIPIDAEMIC RABBITS FOLLOWING TREATMENT WITH CHOLESTYRAMINE OR PRAVASTATIN
Authors: Mamo J. C. L. , Bowler A. , Redgrave T. G. , Elsegood C. L. 
Published: June 2007

SUMMARY1. Cholestyramine and pravastatin are two potent hypocholesterolaemic drugs which lower plasma cholesterol by increasing the clearance of low density lipoproteins by high affinity uptake mechanisms.2. We gave heterozygous Watanabe heritable hyperlipidaemic rabbits (hz‐WHHL) cholestyramine and/or pravastatin for a two week period to try and ameliorate slow clearance of chylomicron remnants, which occurs because of reduced expression of the apolipoprotein B100/E receptor.3. In hz‐WHHL rabbits the clearance of chylomicron‐like lipid emulsions, traced by the decrease in plasma cholesteryl oleate radioactivity was not improved following treatment with either of the cholesterol lowering drugs.4. In contrast, control rabbits had significantly less chylomicron‐like emulsion cholesteryl‐ester radioactivity remaining at each time of blood sampling.5. Similarly, the clearance of chylomicron‐like emulsion triolein was enhanced in normal rabbits receiving cholestyramine or pravastatin, whereas there was no detectable increase in clearance in hz‐WHHL rabbits.6. Combined treatment with cholestyramine and pravastatin increased the rate of receptor‐mediated uptake in vivo in control rabbits but not in hz‐WHHL rabbits.7. The plasma lipid profiles of control and hz‐WHHL rabbits parallelled the patterns of chylomicron‐like emulsion clearance. Moderate hypertriglyceridaemia was identified in hz‐WHHL rabbits compared to controls and there was no change in plasma triglyceride or cholesterol following drug therapy. In contrast, control rabbits had decreased plasma lipids following cholestyramine or pravastatin treatment.8. It appears that therapy with lipid lowering drugs increased chylomicron remnant clearance in control rabbits by up‐regulation of the apolipoprotein BIOO/E receptor. In contrast, in hz‐WHHL rabbits receptor activity did not appear to be increased sufficiently to ameliorate defective remnant clearance. We have suggested that a critical receptor density is required for efficient remnant clearance.
DISEASE‐INDUCED CHANGES IN α‐ADRENOCEPTOR‐MEDIATED CARDIAC AND VASCULAR RESPONSES IN RATS
Authors: Brown Lindsay , Amos Gregory , Miller Brendan 
Published: June 2007

SUMMARY1. The physiological relevance of cardiac and vascular α‐adrenoceptors may increase in disease states in which β‐adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally‐induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR).2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR.3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats.4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats.5. Thus, disease states which alter β‐adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the α1‐adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via α‐adrenoceptors.