bluuebunny/crossref_metadata_2025 huggingface dataset:
SIMULATION OF ACUTE HAEMORRHAGE IN UNANAESTHETIZED RABBITS
Authors: Ludbrook John , Potocnik Simon J. , Woods Robyn L.
Published: June 2007

1. We have shown that it is feasible to match the linear rate of fall of cardiac output that occurs during haemorrhage at 2.7 ml/kg per min in unanaesthetized rabbits by constricting the thoracic inferior vena cava so as to decrease venous return.

2. The changes in systemic vascular resistance, arterial pressure and heart rate that occurred during haemorrhage were mimicked by simulated haemorrhage. They were reproducible when simulated haemorrhage was performed three times at 90 min intervals, and when it was repeated four times over 12 days.

3. Simulated haemorrhage caused rises in plasma renin activity (PRA) and plasma arginine vasopressin concentration (AVP) that were similar to those reported after haemorrhage. The response of PRA was unaffected by repeated simulated haemorrhage, but the response of AVP was less on the third occasion.

4. When the shed blood was re‐infused after haemorrhage, cardiac output tended to remain low and systemic vascular resistance high. After simulated haemorrhage, all haemodynamic variables returned to normal within 2 min of releasing the caval cuff.

5. Haematocrit fell during haemorrhage, and remained low for at least 5 days after replacement of the shed blood. Haematocrit was unaffected by simulated haemorrhage.

6. Venous pressure below the inflatable cuff rose by 6 mmHg in the course of simulated haemorrhage.

7. We conclude that the central haemodynamic effects of haemorrhage can be closely and repeatedly simulated by inflating a cuff on the inferior vena cava. This provides a useful technique for repeatedly studying the effects of acute reduction of central blood volume in conscious animals.
INTERACTION BETWEEN ATRIAL NATRIURETIC FACTOR AND OUABAIN: VASCULAR REACTIVITY TO NORADRENALINE IN PENTOBARBITAL ANAESTHETIZED DOGS
Authors: Chintala Madhu S. , Jandhyala Bhagavan S.
Published: June 2007

1. The influence of intra‐arterial infusion of rat atrial natriuretic factor (ANF 8–33) and/or ouabain on the vascular responses to noradrenaline was investigated in the denervated and flow‐controlled hindlimb preparations in pentobarbital anaesthetized dogs.

2. During the continuous infusions of ANF (30–40 min) vascular responses to noradrenaline were significantly depressed. Subsequent infusion of ouabain together with ANF (50–60 min) reversed and restored the vascular reactivity to the control levels. Hypotension produced by ANF infusion was partially reversed during the simultaneous infusions of both the agents.

3. In a separate series of experiments, in which ouabain was first infused (50–60 min) vascular responses to noradrenaline were significantly enhanced. Subsequent infusions of ANF (plus ouabain) even up to 60 min or longer failed to alter the enhanced vascular responsiveness facilitated by ouabain.

4. The present studies demonstrate a physiological antagonism between ANF and ouabain and such a phenomenon could account for the previous observation that vascular reactivity to noradrenaline was progressively enhanced after acute blood volume expansion. Whereas plasma levels of both ANF and ouabain‐like inhibitor(s) of the sodium pump are elevated after volume expansion, inhibitory effects of ANF on the vascular smooth muscle may be compromised in the presence of an Na+ pump inhibitor(s).
NEUROCHEMISTRY OF THE SYMPATHETIC INNERVATION TO THE UTERUS
Authors: Bell C. , Malcolm S. J.
Published: June 2007

1. The uterus is supplied by numerous noradrenergic sympathetic nerve fibres, which supply the intramural vasculature and also, in some species at least, the myometrium.

2. Pregnancy is associated with progressive loss of catecholamine from these nerves. Although some direct mechanical damage due to stretching of the uterine wall contributes to this effect, it is primarily due to hormonal influences.

3. In animal experiments, the changes in uterine catecholamine occurring during pregnancy are mimicked by intra‐uterine administration of progesterone.

4. The action of progesterone appears not to be selective for pelvic sympathetic neurons, or those in which transmitter turnover rate is particularly slow. The mechanism of depletion is probably through inhibition of tyrosine hydroxylase activity.

5. The functional role of this phenomenon during pregnancy, if one exists, seems likely to be related to protection of the fetoplacental blood supply against sympathetically mediated vasospasm. It is also possible that circulating progesterone may have a general inhibitory action on the female sympathetic nervous system.
CATECHOLAMINE INACTIVATION IN UTERINE TISSUES: CHANGES IN PREGNANCY IN THE RAT
Authors: Kennedy J. A. , de la Lande I. S.
Published: June 2007

1. In vitro metabolism of [3H]‐(—)‐noradrenaline (3H‐NA), 0.2 μmol/l, was measured in rat endometrial and myometrial slices at different stages of gestation and compared with that in dioestrous rats. Metabolism of 3H‐NA, 0.2 μmol/l, was measured in rat placental slices from day 14 of gestation onwards.

2. 3H‐NA was metabolized mainly by deamination in rat myometrium, with [3H]‐3,4‐dihydroxyphenylethylene glycol, (3H‐DOPEG) being the major metabolite. Cocaine, 30 μmol/l, inhibited 3H‐DOPEG formation and the amount of 3H‐NA remaining in the tissue. O‐methylated metabolite formation was unaffected by cocaine.

3. O‐methylation and deamination were equally active pathways for metabolizing 3H‐NA in rat endometrium. O‐methylation to [3H]‐normetanephrine (3H‐NMN) predominated in the placenta. In both tissues O‐methylated metabolite formation was inhibited by 30 μmol/l cocaine.

4. In myometrium, metabolite formation per gram was constant in the first half of pregnancy and was similar to that in dioestrous animals. By day 17 of gestation, however, [3H]‐O‐methylated deaminated metabolites (3H‐OMDA), comprising 3‐methoxy, 4‐hydroxy‐phenylethylene glycol and vanillylmandelic acid, and 3H‐NMN formation were less than in dioestrous animals.

5. Endometrial 3H‐NMN and 3H‐DOPEG formation per gram were higher in rats at day 5 of gestation than in dioestrous rats but metabolite formation per gram declined thereafter to reach values equal to (3H‐DOPEG) or less than (3H‐OMDA and 3H‐NMN) those in dioestrous rats.

6. 3H‐NMN and 3H‐OMDA formation per gram decreased from day 14 to day 20 of gestation in rat placentae.

7. The lack of evidence for increased O‐methylation of noradrenaline in rat endometrium or myometrium in late pregnancy contrasts with previous reports of increased catechol‐O‐methyltransferase activity in the pregnant rat uterus.
ENZYME INDUCTION BY EATING CHARCOAL‐GRILLED STEAK WITH NO EFFECT ON BLOOD LIPIDS
Authors: Heller R. F. , Henry D. A. , Brent P. J.
Published: June 2007

1. There has been interest in the suggestion that enzyme‐inducing drugs, such as anticonvulsants, may produce beneficial changes in lipoprotein levels, in particular a rise in the ratio of high density lipoprotein cholesterol to total cholesterol.

2. This controlled study observed the effects of diets of charcoal or oven‐cooked beef on antipyrine clearance (a commonly used measure of drug metabolizing capacity), the apparent oral clearance of phenacetin (a measure of cytochrome P448‐dependent enzyme activity) and blood lipids in 18 healthy volunteers.

3. Charcoal‐cooked beef increased antipyrine clearance by an average of 20% (P < 0.059) and increased the apparent oral clearance of phenacetin fivefold (P < 0.01). In contrast, oven‐cooked beef did not significantly alter either measure of microsomal function. Neither diet had any effects on blood lipids.

4. We conclude that the type and degree of enzyme induction achieved by this type of dietary manipulation does not produce beneficial changes in lipoprotein profiles. A previously noted rise in high density lipoprotein cholesterol levels in volunteers fed charcoal‐cooked beef may have been due to the effects of charcoal formed by charring of the beef during cooking.
EFFECT OF DILTIAZEM, VERAPAMIL AND DANTROLENE ON THE CONTRACTILITY OF ISOLATED MALIGNANT HYPERPYREXIA‐SUSCEPTIBLE HUMAN SKELETAL MUSCLE
Authors: Foster P. S. , Hopkinson K. C. , Denborough M. A.
Published: June 2007

1. Diltiazem (10 μmol/L) and verapamil (10 μmol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures.

2. Like the skeletal muscle relaxant dantrolene sodium (6 μmol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine.

3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive.

4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca2+ influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome.

5. These results also suggest an abnormality in transverse tubule—sarcoplasmic reticulum communication.
EFFECTS OF SUBACUTE OPIOID ADMINISTRATION DURING LATE PREGNANCY IN THE RAT ON THE INITIATION, DURATION AND OUTCOME OF PARTURITION AND MATERNAL LEVELS OF OXYTOCIN AND ARGININE VASOPRESSIN
Authors: Evans R. G. , Olley J. E. , Rice G. E. , Abrahams J. M.
Published: June 2007

1. The effects, on parturition in the rat, of subacute and acute opioid administration were studied. Further experiments investigated the role of modulation of maternal plasma and pituitary oxytocin (OXY) and arginine vasopressin (AVP) levels in these effects.

2. Subacute opioid (M320, buaprenorphine or bremazocine) administration prolonged the gestation of rats. This was accompanied by toxic effects on the offspring. Acute subcutaneous (s.c.) M320 (10 μg/kg) administration was accompanied by prolonged gestation without toxic effects.

3. Subacute M320 (10 μg/kg, s.c., twice daily) treatment was accompanied by increased interbirth intervals in parturient rats.

4. Maternal OXY but not AVP release, as assessed by measurement of plasma and pituitary immunoreactivity, was elevated during and up to 1 h after the completion of parturition. Subacute M320 treatment did not inhibit this elevated OXY release.
DIGOXIN ENHANCES THE PRESSOR RESPONSE TO ALDOSTERONE ADMINISTRATION IN CONSCIOUS SHEEP
Authors: Spence Campbell D. , Coghlan John P. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. This study examined the hypothesis that inhibition of Na, K ATPase with digoxin would enhance the pressor response to aldosterone infusion in conscious sheep.

2. While intravenous infusion of digoxin (10 μg/kg per day for 5 days) had no effect on blood pressure and aldosterone infusion (6 μg/kg per day for 5 days) increased blood pressure by 7 mmHg, combined infusion of digoxin and aldosterone increased blood pressure by 17 mmHg.

3. The metabolic effects of the combined digoxin and aldosterone infusion were similar to those for aldosterone alone, suggesting that digoxin did not enhance the mineralocorticoid action of aldosterone.

4. The results of this study suggest that changes in Na influx (aldosterone‐dependent) and efflux (digoxin‐dependent) are important in the genesis of aldosterone‐induced hypertension.
EFFECTS OF ALTITUDE ON ATRIAL NATRIURETIC PEPTIDE: THE BICENTENNIAL MOUNT EVEREST EXPEDITION
Authors: Tunny Terry J. , van Gelder James , Gordon Richard D. , Klemm Shelley A. , Hamlet Stephen M. , Finn Wendy L. , Carney Gavin M. , Brand‐Maher Carol
Published: June 2007

1. Overnight recumbent atrial natriuretic peptide levels were significantly elevated in all ten subjects of the Australian Bicentennial Mount Everest Expedition during the first week at 5400 m, during acclimatization.

2. Twenty‐four hour urine volume and urine sodium increased markedly at altitude.

3. Plasma renin activity and plasma aldosterone levels decreased significantly at altitude.

4. No significant changes in plasma cortisol, plasma sodium or potassium, body temperature, systolic or diastolic blood pressure or heart rate were observed.

5. Although it was impossible to control or measure salt and water intake during the study, results suggest that atrial natriuretic peptide may be important in the reduction in renin and aldosterone levels and in the diuresis and natriuresis necessary to adapt to hypoxia at altitude.
MOUSE ASTROCYTES POSSESS SPECIFIC ANP RECEPTORS WHICH ARE LINKED TO cGMP PRODUCTION
Authors: Teoh R. , Kum W. , Cockram C. S. , Young J. D. , Nicholls M. G.
Published: June 2007

1. Receptors for atrial natriuretic peptide (ANP) have been identified on mouse astrocytes in primary culture, and have similar characteristics to those found on previously recognized ANP‐target tissues.

2. Scatchard analysis revealed one class of high affinity receptors with a Kd of 0.32 nmol/L. The IC50 for specific binding was 0.5 nmol/L.

3. Ligand binding resulted in stimulation of guanylate cyclase.

4. Under reducing conditions, the covalently cross‐linked receptor‐ANP complex migrated on SDS‐polyacrylamide gels as a single band with an apparent molecular weight of 66 kDa.

5. Although the physiological relevance of our observations remains to be determined, these data document that cultured mouse astrocytes contain specific high‐affinity ANP receptors which are linked to the production of cGMP.
BLOOD PRESSURE RESPONSE TO NOREPINEPHRINE AND ANGIOTENSIN II IN THE OFFSPRING OF PARATHYROIDECTOMIZED MOTHER RATS
Authors: Nakanishi Hitoshi , Fujii Tomoko
Published: June 2007

1. The basal blood pressure and the drug‐stimulated pressor response were studied in male offspring in the sixth generation (5d‐PTx‐F6) of rats parathyroidectomized on day 5 of pregnancy.

2. The systolic blood pressure in conscious 5d‐PTx‐F6 rats measured by a tail cuff was significantly higher (P < 0.001) than in control rats.

3. Venous plasma renin activity was significantly lower (P < 0.001) in the 5d‐PTx‐F6 rats. Plasma levels of calcium, sodium, and potassium in the 5d‐PTx‐F6 rats and in the controls did not differ.

4. Systolic arterial pressure response to intravenously (i.v.) administered angiotensin II (150 ng/kg) in the 5d‐PTx‐F6 rats was significantly greater than in the controls (P < 0.05), when blood pressure was measured directly through a pressure transducer under anaesthesia.

5. Pressor responses to norepinephrine (5 μg/kg, i.v.) in the 5d‐PTx‐F6 rats were significantly lower (P < 0.05) than in the controls, when blood pressure was measured directly under anaesthesia.

6. The findings suggest that the 5d‐PTx‐F6 rats undergo functional alterations of the renin‐angiotensin and sympathetic nervous systems for cardiovascular regulations.
CALCIUM CONTENT OF THE ERYTHROCYTES: A SENSITIVE AND EASY HANDLING METHOD FOR MEASURING FREE CALCIUM IONS, AND MODULATION OF THE Ca2+ ION CONCENTRATION BY THE CALCIUM ANTAGONISTS NIFEDIPINE AND PENTOXIFYLLINE
Authors: Friederichs E. , Rädisch T. , Winkler H.
Published: June 2007

1. A method for determining free Ca2+‐ions in the erythrocyte is described, using a commercially available ORION‐Ca‐electrode and calomel reference electrode assembly, where changes in free Ca2+‐ion concentration upon addition of 0.01% digitonin could be measured.

2. The average value found for fresh cells from 20 healthy donors at 37°C (pH = 7.4) was 0.20 ± 0.04 μmol/L referred to a haematocrit of 10%.

3. Decrease of the simultaneously determined adenosinetriphosphate (ATP) concentration indicates that ATP is presumably needed to activate the Ca‐ATPase.

4. In vitro addition of the calcium antagonists pentoxifylline and nifidepine, respectively, induced a normalization of the intraerythrocytic Ca2+‐ion concentration after previous increase with the ion carrier ionophore A23187.

5. The advantages and possible clinical applications of this method are discussed.
CORTICAL CONTROL OF TONGUE CONTRACTILITY IN THE RAT UNDER KETAMINE ANAESTHESIA
Authors: Marco L. A. , Reed T. F. , Aides L. D. , Chronister R. B. , Brown C. B. , White L. E.
Published: June 2007

1. Cortico‐lingual and linguo‐cortical interconnectivity was investigated in ketamine‐anaesthetized rats mounted onto a stereotaxic apparatus. The tip of the tongue was tied to a force displacement transducer to monitor tongue retrusions. The tongue cortical area was exposed in one or both hemispheres to record evoked potentials or spontaneous electroencephalographic (EEG) activity, or to stimulate electrically with single square pulses of up to 50 V and 0.25 ms pulse width.

2. The results showed that (i) tongue retrusions elicited by electrical stimulation were identical to those induced by ketamine; (ii) ketamine‐induced tongue contractions correlated in time with cortical EEG potentials which were easily distinguished from the background noise; (iii) haloperidol (2.5 mg/kg, i.m.) suppressed the cortically evoked tongue contractions as well as the ketamine‐induced contractions.

3. These results suggest that ketamine‐induced tongue retrusions may involve the cortex in their mediation if not their generation and that this may provide a basis for the suppression of dyskinetic activity during sleep or unconsciousness.
DETERMINANTS OF SMOOTH MUSCLE SENSITIVITY
Authors: Head Richard J.
Published: June 2007

1. Deviation supersensitivity and post‐junctional supersensitivity are important determinants in the control of the response of smooth muscle.

2. Post‐junctional supersensitivity is a process whereby effector cells have augmented responsiveness as a consequence of an impaired physiological stimulus. Deviation supersensitivity which occurs as a result of inhibition of sites of loss or inactivation of the transmitter substance noradrenaline and its analogues also produces an enhanced response of smooth muscle cell preparations.

3. The enzymes monoamine oxidase and catechol‐O‐methyl transferase are irreversible sites of loss of noradrenaline. Functional impairment of these enzymes results in deviation supersensitivity.

4. The complexities involved in unravelling the contribution of noradrenaline metabolizing enzymes to deviation supersensitivity are highlighted with emphasis upon the pioneering work of Professor de la Lande in this field.
MECHANISMS OF ADAPTIVE SUPERSENSITIVITY IN SMOOTH MUSCLES VS CARDIAC MUSCLE: A BRIEF REVIEW
Authors: Fleming William W.
Published: June 2007

1. Depending upon the type of cell being studied, adaptive supersensitivity has been traced to molecular changes in receptors, the Na+/K+ pump or the G‐protein/adenylate cyclase system.

2. Evidence is reviewed that indicates that adaptive supersensitivity in guinea‐pig atria is the result of changes in the G‐protein/adenylate cyclase system.
CYTOCHROMES P‐450 IN STEROIDOGENESIS: ARE THESE ENZYMES MORE SPECIFIC THAN THOSE OF DRUG METABOLISM?
Authors: Hall Peter F.
Published: June 2007

1. In contrast to drug‐metabolizing cytochromes P‐450, the corresponding ster‐oidogenic enzymes appear to be highly specific with respect to substrates, reactions catalysed, and the sites in the substrate molecule that are attacked.

2. Recent studies have shown that important exceptions to this generalization are encountered.

3. The conversion of 11‐deoxycorticosterone to aldosterone requires three enzymatic reactions, the last of which (aldehyde synthetase), like the first two, requires a P‐450 mono‐oxygenation. The involvement of P‐450 in this third step (from alcohol to aldehyde) was demonstrated by photochemical action spectra and determination of stoichiometry. The three reactions were shown to be catalysed by a single enzyme as demonstrated by immunoprecipitation and the use of a homogenous enzyme.

4. The conversion of pregnenolone and progesterone to the corresponding Δ16‐C19 steroids, which are pheromones, is catalysed by a cytochrome P‐450 that also catalyses the conversion of progesterone to androstenedione (that is, C21 side‐chain cleavage; hydroxylase/lyase). The synthesis of the Δ16 compounds requires cytochrome b5.

5. The conversion of testosterone and epitestosterone to androstenedione is catalysed by P‐450b. Studies of kinetic isotope effects using deuterium and 18O2 show that P‐450b catalyses this reaction with epitestosterone via the formation of a gem diol, whereas, with testosterone as substrate, one‐third of the product is formed via the same mechanism while the remainder results from the mechanism described as dual hydrogen abstraction.
THE ROLE OF CYTOCHROMES P‐450 AND N‐ACETYL TRANSFERASE IN THE CARCINOGENICITY OF AROMATIC AMINES AND AMIDES
Authors: McManus Michael E.
Published: June 2007

1. Epidemiological studies have clearly identified the aromatic amines 2‐naph‐thylamine, benzidine and 4‐aminobiphenyl as human carcinogens. Many other compounds of this class are suspected to be human carcinogens.

2. At least 12 heterocyclic aromatic amines have been isolated from cooked food, nine of which have been shown to be carcinogenic in vivo. The significance of these compounds in the aetiology of human cancer is yet to be established.

3. Specific forms of cytochrome P‐450 have been shown to be involved in the initial step in the activation (N‐hydroxylation) of aromatic amines and amides. A possible polymorphism exists for the N‐hydroxylation of 2‐acetylaminofluorene in human liver microsomes.

4. N‐Acetyltransferase is involved in the further activation of arylhydroxamic acids and N‐hydroxyarylamines to reactive intermediates. Polymorphisms in the expression of this enzyme activity have been associated with certain types of human cancer.

5. Polymorphisms in both cytochrome P‐450 and N‐acetyltransferase expression may be critical determinants in the susceptibility of individuals to the toxicity and carcinogenicity of aromatic amines and amides.
ISOMETRIC CONTRACTILE PROPERTIES AND CAFFEINE SENSITIVITY OF THE DIAPHRAGM, EDL AND SOLEUS IN THE MOUSE
Authors: Singh Yadhu N. , Dryden William F.
Published: June 2007

1. Isometric contractile responses and caffeine sensitivity were studied in isolated mouse hemidiaphragm (HD), extensor digitorum longus (EDL) and soleus muscles.

2. The maximum twitch and tetanic tensions developed by the EDL showed a greater temperature dependence than the soleus. The rates of force development and relaxation were more temperature sensitive in the soleus.

3. For the HD, Q10 values for all contractile parameters were intermediate between those of the EDL and the soleus but closer to those of the EDL.

4. The soleus was significantly more sensitive to caffeine than the EDL while the HD showed a response closer to that of the EDL than the soleus.

5. Costal segments of the HD developed force more rapidly but were less caffeine sensitive than the vertebral or sternal segments.

6. The results indicate that the mouse HD exhibits isometric contractile characteristics and caffeine sensitivity more closely resembling the EDL than the soleus but there is a variation in these properties between the different parts of the HD.
TAURINE: EFFECT ON MYOCARDIAL RELAXATION
Authors: Rahimi A. R. , Campbell K. B. , Knowlen G. G. , Kirkpatrick R. D.
Published: June 2007

1. The effects of taurine on cardiac inotropic state and relaxation were studied in the isolated rabbit heart using solutions containing three concentrations of calcium: 0.7, 1.8 and 3.0 mmol/l.

2. Increases in Ca2+ caused increases in inotropic indices, but had no effect on rate constant of relaxation.

3. Taurine had a positive inotropic effect at Ca2+= 0.7 mmol/l, an equivocal effect at Ca2+= 1.8 mmol/l and a negative inotropic effect at Ca2+= 3.0 mmol/l.

4. Taurine had no effect on the rate constant of relaxation at any Ca2+ concentration.

5. Taurine modulates the positive inotropic effect of Ca2+ but neither taurine nor Ca2+ affect the rate constant of relaxation.
ACUTE HORMONAL AND RENAL EFFECTS OF ORAL DILEVALOL IN NORMAL MEN
Authors: Whitworth Judith A. , Gordon Deanna , Harpley Robin , Yeung Stella , Phillips Paddy
Published: June 2007

1. Acute hormonal and renal effects of dilevalol (200 mg), a non‐selective β‐blocking drug with vasodilator properties, were compared with placebo in six normal men on constant sodium intake.

2. Control and treatment blood pressures were lower with dilevalol than placebo, although the pattern of blood pressure fall was similar in both.

3. Plasma active renin and aldosterone concentrations were lower on dilevalol than placebo after 4 h of recumbency (P < 0.05).

4. Total plasma renin, renin substrate, cortisol and atrial natriuretic peptide concentrations were similar on dilevalol and placebo.

5. There were no differences in glomerular filtration rate and no deleterious biochemical or haematological changes on dilevalol or placebo.
IN VITRO TIME COURSE STUDIES ON TRAIN‐OF‐FOUR FADE INDUCED BY HEXAMETHONIUM, PANCURONIUM AND DECAMETHONIUM IN THE RAT HEMIDIAPHRAGM
Authors: Gwee M. C. E. , Cheah L. S.
Published: June 2007

1. In vitro time course studies on the effects of hexamethonium (7 mmol/L), pancuronium (5 μmol/L) and decamethonium (220 μmol/L) on nerve‐evoked (2 Hz for 2 s every 20 s) maximal twitches (T1, T2, T3, T4) of the rat hemidiaphragm were conducted. All three drugs progressively depressed all four twitches in a given train but at different rates (T4 > T3 > T2≫ T1).

2. The response‐time profiles for T1 and T4 varied widely for the three drugs such that, for the same degree of T1‐block, each drug produced a different magnitude of T4‐block during the onset of and recovery from neuromuscular blockade.

3. Analysis of the T1 versus T4/T1 plot showed that, at 50% T1‐block, the corresponding T4/T1 (i.e. train‐of‐four ratios) during the onset (and recovery) phase were 0.16 (0.29), 0.46 (0.40) and 0.66 (0.53) for hexamethonium, pancuronium and decamethonium, respectively. Thus, for the same degree (i.e. 50%) of twitch (T1) tension depression, the three drugs differed widely in their ability (hexamethonium ≫ pancuronium > decamethonium) to produce fade as reflected in the respective train‐of‐four ratio.

4. Our results therefore show that the train‐of‐four ratio (T4/T1) at 50% T1‐block obtained from such in vitro time course studies is a useful quantitative index of the potential of various drugs to cause train‐of‐four fade. Based on this index a classification of various compounds already studied is proposed as follows: hexamethonium ≫ pancuronium ∼ (+)‐tubocurarine > decamethonium ∼ succinylcholine ≫α‐bungarotoxin.
STIMULATION OF β1‐ADRENOCEPTORS ENHANCES ELECTRICALLY EVOKED [3H]‐ACETYLCHOLINE RELEASE FROM RAT PHRENIC NERVE
Authors: Wessler I. , Holzer G. , Künster A.
Published: June 2007

1. The effects of isoprenaline, noradrenaline and fenoterol on the electrically evoked release of [3H]‐acetylcholine from the rat phrenic nerve were investigated.

2. Isoprenaline (0.1 μmol/L) and noradrenaline (1 μmol/L) enhanced evoked [3H]‐acetylcholine release by about 90%, an effect which was abolished by CGP 20712A (0.1 μmol/L), a specific antagonist at β1‐adrenoceptors. Noradrenaline still enhanced [3H]‐acetylcholine release in the presence of phentolamine (1 μmol/L).

3. The enhancing effect of both isoprenaline and noradrenaline decreased at prolonged exposure times (24–32 min). A pre‐exposure of the tissue to a low concentration (0.01 μmol/L) of isoprenaline prevented the enhancing effect of 0.1 μmol/L isoprenaline.

4. Fenoterol, a specific agonist at β2‐adrenoceptors, did not modify evoked [3H]‐acetylcholine release.

5. The present results indicate the existence of facilitatory β1‐adrenoceptors on the motor nerve. These receptors appear to be desensitized either by a high concentration of, or by a long exposure to, agonists. Under the present conditions noradrenaline enhances the release of newly synthesized transmitter mainly by stimulation of β‐adrenoceptors.
SYSTEMIC AND REGIONAL EFFECTS OF ENDOTHELIN IN RABBITS: EFFECTS OF ENDOTHELIN ANTIBODY
Authors: Miyamori I. , Itoh Y. , Matsubara T. , Koshida H. , Takeda R.
Published: June 2007

1. The effects of porcine endothelin‐1 (10‐12‐5 × 10‐10mol/kg) on arterial blood pressure (BP) and the renal, mesenteric and carotid blood flow (BF), and the effects of endothelin‐1 antibody were studied in rabbits.

2. Endothelin‐1 caused a sustained increase in BP. The renal, mesenteric and carotid BF were decreased dose‐dependently by endothelin‐1. The approximate half‐maximal effective values (ED50) were 5.5 × 10‐11, 8.6 × 10‐11 and 2.0 × 10‐10 mol/kg for renal, mesenteric and carotid BF respectively. Compared with carotid BF, the renal and mesenteric BF responses were significantly more sensitive to endothelin‐1.

3. Combined administration of endothelin‐1 and its antibody showed a significant inhibition of the BP and renal BF responses. However, endothelin‐1 antibody alone did not change either BP, renal BF, mesenteric BF or carotid BF in vivo.

4. The present results demonstrate that endothelin is a potent vasoconstrictor in vivo. However, circulating endothelin may not contribute to the control of BF and BP. The role of endothelin as a local modulator of the vascular tone remains to be investigated.
EFFECTS OF THE α2‐ADRENOCEPTOR AGONIST UK14304 ON PRESSOR RESPONSES IN PITHED RATS
Authors: Xiao X‐H. , Rand M. J.
Published: June 2007

1. Intravenous infusions of UK14304 (0.3–10 μg/kg per min) in pithed rat produced dose‐dependent pressor responses which were not affected by prazosin (10 μg/kg) but were reduced by yohimbine (0.3 mg/kg).

2. Pressor responses to noradrenaline (0.1 μg/kg), phenylephrine (1 μg/kg) and vasopressin (10 mU/kg) were enhanced during infusions of UK14304 (0.03–1 μg/kg per min). Likewise, pressor responses to spinal sympathetic stimulation were enhanced during infusions of low concentrations of UK14304 (0.03–0.3 μg/kg per min) but were reduced during infusion of a higher concentration of UK14304 (10 μg/kg per min).

3. After administration of yohimbine (0.3 mg/kg) or the calcium channel blocking drug diltiazem (infused at 50 μg/kg per min), pressor responses to noradrenaline and UK14304 were reduced, and responses to noradrenaline during infusion of UK14304 were not enhanced.

4. Prazosin (10 μg/kg) revealed a secondary depressor component in the response to sympathetic stimulation which is due to β‐adrenoceptor activation, since it was abolished by ICI 118551 (0.3 mg/kg). In the presence of ICI 118551 plus prazosin, pressor responses to sympathetic stimulation were enhanced during infusions of UK14304.

5. The depressor response to nitroprusside and the depressor component of responses to sympathetic stimulation after prazosin were enhanced during infusions of UK14304 at concentrations that increased the blood pressure.

6. The findings show that α2‐adrenoceptor activation enhanced the pressor responses to sympathetic nerve stimulation, noradrenaline, phenylephrine and vasopressin in the pithed rat and α‐adrenoceptor activation produced depressor responses which increased with increasing blood pressure.
THE EFFECT OF IVERMECTIN ON SOME HAEMATOLOGICAL INDICES IN RABBITS: INFLUENCE OF VITAMIN K TREATMENT
Authors: Ali B. H.
Published: June 2007

1. Rabbits were treated with the antiparasitic drug ivermectin at subcutaneous doses of 0.2, 1 and 2.5 mg/kg and blood collected weekly for 4 weeks thereafter for measuring some blood parameters. At a dose of 0.2 or 1 mg/kg the drug had no significant effect on any of the parameters measured. At a dose of 2.5 mg/kg, the drug reduced significantly the erythrocyte counts, haemoglobin concentration, haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular haemoglobin on weeks 1, 2, 3 and 4. Platelet counts were not significantly affected.

2. In another trial, ivermectin was injected subcutaneously at a dose of 2.5 mg/kg, after pre‐treatment with either saline or vitamin K (30 μg/kg for 30 days), and prothrombin time, bleeding time and platelet counts measured at weekly intervals for 4 weeks. Bleeding time and thrombin time were significantly increased 1 week after treatment, and remained higher than the control for 4 weeks.
PROGNOSIS OF MALE PATIENTS WITH TREATED HYPERTENSION FOLLOWED OVER 15 YEARS
Authors: Morgan Trefor O. , Anderson Adrianne , Hopper John , Maskill Greg
Published: June 2007

1. Male patients aged 50–75 years on treatment for hypertension in 1973 have been followed for 15 years.

2. Overall mortality in the 271 patients was 63% and 41% died of vascular disease.

3. Coronary artery disease or sudden death occurred in 44% of the patients who died and was between 2 and 6 times more common than in the general population.

4. Treatment of hypertension has improved overall prognosis but mortality from coronary artery disease is more common than in the general population.
HIGH SALT DIET AMELIORATES EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITION IN SPONTANEOUSLY HYPERTENSIVE STREPTOZOTOCIN DIABETIC RATS
Authors: Jackson Bruce , Fabris Bruno , Paxton Donna , Franze Linda , Johnston Colin I.
Published: June 2007

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet.

2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period.

3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P<0.001).

4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P<0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160±30 mg/day in Group 1, 240±50 mg/day in Group 2, and 60±11 mg/day in Group 3.

5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.
URIDINE KINASE INHIBITION IS INVOLVED IN THE VASODILATOR EFFECTS OF MINOXIDIL IN THE RAT
Authors: Macdonald Graham , Walker Therese , Assef Rhonda , Duggan Karen
Published: June 2007

1. Since minoxidil is a pyrimidine derivative, its actions on vascular smooth muscle may derive from structural relationships to the uridine nucleotides, which have been shown to be vasoconstrictive in the rat.

2. Minoxidil at a low vasodepressor dose of 0.03 mg/kg per min abolished the pressor response to uridine at doses from 2 to 8 μmol/kg per min, but did not reduce the responses to uridine monophosphate or uridine diphosphate in similar pressor doses, suggesting an action on either transport of uridine into cells or on uridine kinase which catalyses phosphorylation of uridine to uridine monophosphate, the mediator of uridine's vascular actions.

3. The active metabolite of minoxidil was found to inhibit rat liver uridine kinase in vivo using an HPLC technique.

4. Plasma uridine concentration was significantly higher in 11 hypertensive patients on minoxidil compared with pretreatment values, suggesting that uridine kinase inhibition is of a degree sufficient to increase the circulating pool of uridine.

5. The data is consistent with uridine kinase inhibition being a mechanism for the vasodilator actions of minoxidil.
LACK OF PRESSOR RESPONSE TO INTRACEREBROVENTRICULAR INFUSION OF ALDOSTERONE IN SHEEP
Authors: Tresham Janette J. , Coghlan John P. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. Studies in the rat and the dog have shown that infusion of aldosterone for several weeks into the cerebral ventricles (ICV) can produce hypertension at doses that do not have an effect when infused systemically. We have previously shown that a high physiological dose of aldosterone infused intravenously at 10 μg/h in sheep produces an increase in blood pressure of 7 mmHg within 2 days.

2. In this paper we report the effects of ICV infusion of aldosterone at 2 μg/h for 6 days in conscious sheep.

3. Neither blood pressure nor heart rate were altered, and there were no consistent changes in any of the metabolic parameters measured.

4. These results do not support a role for central effects of aldosterone in the hypertension produced by systemic infusion of the steroid in sheep.
PLASMA AND PITUITARY THYROID‐STIMULATING HORMONE LEVELS IN BROMOCRIPTINE‐TREATED NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Tan B. K. H. , Hutchinson J. S.
Published: June 2007

1. The effects of a 13‐day intraperitoneal (i.p.) infusion of bromocriptine, delivered by osmotic pump, on plasma and pituitary thyroid‐stimulating hormone (TSH) levels were investigated in New Zealand genetically hypertensive (GH) rats and their normotensive (NT) controls.

2. In both the GH and NT rats, bromocriptine significantly reduced plasma TSH level but did not have any significant effect on pituitary TSH content.

3. No significant difference was found in the plasma TSH level and pituitary TSH content between the vehicle‐treated GH and NT rats.

4. These results suggest that there are no differences between the GH and NT rats with regard to the activity of the central dopaminergic system influencing TSH release and also that TSH does not play a role in the hypertension of the GH rats.
IN VIVO GENERATION AND ELIMINATION OF ANGIOTENSIN IN THE RAT
Authors: Jacobsen Jørgen , Poulsen Knud
Published: June 2007

1. Combined high performance liquid chromatography (HPLC) and radioimmunoassays were used to study the in vivo kinetics of the renin‐angiotensin system in the rat. The HPLC‐verified plasma concentrations of angiotensin I (AI) were 1.0 nmol/L (0.52–1.6) in anaesthetized normal and 4.2 nmol/L (2.5–7.0) in salt‐depleted rats. The plasma concentrations of angiotensin II (AII) were 0.07 nmol/L (0.04–0.13) in anaesthetized normal and 1.0 (0.60–1.6) nmol/L in saltdepleted rats.

2. The fate of injected AI and AII passing through the vascular bed of the lungs was determined. Two‐thirds of the injected AI was converted to AII and one‐third was unchanged after a single passage through the lungs. Only trace amounts of angiotensin III (AIII), the only other metabolite, were demonstrated.

3. This verifies that the majority of AI is metabolized through AII. Injected AII disappeared from the circulation with formation of only trace amounts of AIII, the half‐life being about 10 s. This corresponds to a calculated in vivo generation rate of AII of about 12 nmol/L per h in normal rats. It is in agreement with the AI generation rate (plasma renin activity) measured as 9.5 nmol/L per h in vitro.
EFFECTS OF BLOOD GAS/pH ABNORMALITIES ON THE CARDIOVASCULAR ACTIONS OF VERAPAMIL IN RATS
Authors: Achike Francis I. , Dai Soter
Published: June 2007

1. The effects of hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis or hypercarbia with acidosis on the blood pressure and pulse rate responses to verapamil were studied in chloralose‐anaesthetized rats.

2. At a fixed stroke volume (10 mL/kg) and rate (80 strokes/min; except for the hypocarbic group at 160 strokes/min), hypoxaemia, hyperoxaemia, hypercarbia with acidosis, or hypocarbia with alkalosis was induced by artificial ventilation with gas mixtures containing 17% O2, 28% O2, 23% O2, with 5% CO2, or 17% O2, without CO2 respectively. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3 respectively, in animals artificially ventilated with room air.

3. Changes in individual blood gas/pH parameters had no significant effect on blood pressure except for acidosis which caused a significant decrease. Effects on pulse rate were significant increases in the alkalosis and hypercarbia groups, decrease in the acidosis group, while in other conditions no significant changes were recorded.

4. In the controls, intravenous injections of verapamil 20–320 μg/kg caused dose‐dependent increases in mean blood pressure, while effects on pulse rate were not marked.

5. The hypotensive responses to verapamil were significantly alleviated or enhanced in the presence of alkalosis or acidosis respectively. Verapamil also caused greater falls in pulse rate during acidosis. Effects of P02 changes were not statistically significant. The influence of PCO2 changes remained unclear.

6. The present findings suggest that changes in blood pH may play a more important role than P02, alterations in affecting the cardiovascular responses to verapamil in the presence of blood gas abnormalities.
PATHWAYS LINKING RENAL EXCRETION AND ARTERIAL PRESSURE WITH VASCULAR STRUCTURE AND FUNCTION
Authors: Cowley Allen W. , Roman R. J. , Krieger J. E.
Published: June 2007

1. A brief review is presented which summarizes the role of the kidney in the long‐term regulation of arterial pressure and the mechanism whereby changes in body fluid volume can influence the function and structure of the systemic vasculature.

2. Studies indicate that the kidney detects changes of arterial pressure via changes of medullary blood flow which in the volume expanded state is poorly autoregulated. Elevations of renal arterial pressure raise vasa recta capillary pressure and renal interstitial fluid pressure, which in turn reduces tubular reabsorption of sodium and water.

3. The sensitivity of the pressure–diuresis relationship is controlled by renal sympathetic nerve activity and a variety of hormone and autocrine systems.

4. Evidence is also reviewed which shows that small changes of blood volume (5%) resulting from reduced renal excretion can acutely and chronically result in 25% increases of total peripheral resistance and arterial pressure.

5. Short‐term increases of vascular resistance are predicted by regional autoregulatory responses while long‐term elevations of vascular resistance appear to result from the structural changes of large vessel hypertrophy and microvascular rarefaction within skeletal muscle.
THE ACETYLCHOLINE PARADOX: A CONSTRICTOR OF HUMAN SMALL CORONARY ARTERIES EVEN IN THE PRESENCE OF ENDOTHELIUM
Authors: Angus James A. , Cocks Thomas M. , McPherson Grant A. , Broughton Arch
Published: June 2007

1. In animal experiments, acetylcholine is generally a vasodilator acting indirectly by releasing endothelium‐derived relaxing factor (EDRF); for example, in dog and rabbit small coronaries mounted in a myograph, acetylcholine caused concentration‐dependent relaxation.

2. In human small coronary arteries taken from the atrial appendage, however, acetylcholine caused concentration‐dependent contraction with a funcionally intact endothelium as shown by the relaxation in response to substance P, another stimulant of EDRF release.

3. We propose that coronary microvessels from various species have variable populations of acetylcholine receptors on the medial smooth muscle that cause contraction and on the endothelium that cause the release of EDRF. In humans, the medial smooth muscle receptors appear to predominate, and may thus play a role in coronary vasoconstriction.
NORADRENALINE RELEASE FROM THE RAT HEART DURING ANOXIA: EFFECTS OF CHANGES IN EXTRACELLULAR SODIUM CONCENTRATION AND INHIBITION OF SODIUM UPTAKE MECHANISMS
Authors: Dart A. M. , Riemersma R. A.
Published: June 2007

1. Anoxic perfusion of the isolated rat heart releases noradrenaline in the absence of sympathetic nerve fibre stimulation.

2. Anoxic noradrenaline release is enhanced by reducing the extracellular Na+ concentration, consistent with the proposal that such release occurs by carrier‐mediated efflux.

3. Release is also enhanced by lignocaine but inhibited by amiloride and ethylisopropylamiloride, suggesting that sodium entry into adrenergic nerve terminals during anoxia occurs by Na+/H+ (and possibly Na+/Ca2+) exchange.
VOLUNTARY BLOOD PRESSURE CONTROL BY BIOFEEDBACK: RELATIONSHIP TO PSYCHOLOGICAL CHARACTERISTICS
Authors: Hunyor S. N. , Bartrop R. , Craig A. , Cejnar M. , Liggins G. , Henderson R. , Jones M.
Published: June 2007

1. Psychological characteristics were studied in 25 hypertensives (mean and standard deviation of blood pressure 150/95 ± 12/5 mmHg), who received blood pressure (BP) biofeedback (BFB). Personality factors and success in BFB–BP modifying ability were correlated and the predictive value of psychological factors was estimated.

2. Questionnaires consisted of a Locus of Control of Behaviour (LCB) scale, the Spielberger state trait anxiety inventory and the Framingham Type A personality inventory.

3. BP was monitored continuously from the finger by volume clamp plethysmography during eight BFB sessions, each with three trials of raising, ignoring and lowering systolic blood pressure (SP).

4. SP was raised/lowered by 12 ± 11/6 ± 9 mmHg and heart rate (HR) increased by 10 ± 3.9/+ 1 ± 6.1. Ten subjects were able to lower SP by ≥5 mmHg (15 ± 7.5) and raise it by 17 ± 11. The others achieved no decrease in SP and were also less successful at raising (8 mmHg, P= 0.04).

5. Changes in LCB and trait anxiety correlated with DP rise, whereas type A and pre‐study state anxiety correlated with rising HR. Lowering of SP correlated weakly with change in LCB (r= 0.47, P= 0.06).

6. Combinations of psychological factors had independent predictive value for BP and HR change: trait anxiety (P= 0.03) and change in LCB (P= 0.009) with rise in diastolic blood pressure (DP); type A (P= 0.009), pre‐study LCB (P= 0.02) and pre‐study state anxiety (P= 0.01) with HR rise.

7. These findings suggest that psychological factors correlate with BP and HR changes during attempted BFB control of SP. The best predictor for a rise in DP was change in LCB.
A COMPARISON OF THE ANTICONVULSANT EFFECTS OF PROPOFOL AND THIOPENTONE AGAINST PENTYLENETETRAZOL‐INDUCED CONVULSIONS IN THE RAT
Authors: Hasan Zuheir , Hasan Mazen , Al‐Hader AbdelFattah , Takrouri Mohammad
Published: June 2007

1. The anticonvulsant effects of subanaesthetic doses of propofol and thiopentone against PTZ‐induced seizures and mortality were examined in the rat.

2. Administration of propofol (50 mg/kg, i.p.) 5 min prior to PTZ treatment increased the 2 h CD50 and the 24 h LD50 of PTZ by 3.4‐fold, whereas thiopentone pretreatment (20 mg/kg, i.p.) increased these values by more than five‐fold.

3. Both propofol and thiopentone prolonged the latency to the onset of clonic seizure but the effects of the former were more marked.

4. The data demonstrate that propofol was more effective than thiopentone in providing complete protection against PTZ‐induced seizures for the first 30–40 min of observation and that thiopentone, because of its sustained effects, was more effective in reducing the cumulative incidence of seizures and mortality over 2 and 24 h, respectively.

5. We conclude that propofol is a very effective anticonvulsant and provides complete protection of short duration against PTZ‐induced seizures in the rat.
VASOPRESSIN RESPONSE TO HAEMORRHAGE IN RATS: EFFECT OF HYPOXIA AND WATER RESTRICTION
Authors: Raff Hershel , Rossing Mark H. , Doepker Sandra K. , Griffen Steven C. , Jankowski Barbara M.
Published: June 2007

1. The aim of the present study was to determine the effect of water restriction and/or hypoxia on the vasopressin response to haemorrhage in conscious rats.

2. Male, Long‐Evans rats (n= 39) were prepared with chronically indwelling femoral artery and vein catheters and exposed to 24 h of one of the following: normoxia with ad lib drinking water (N + W); normoxia with water restriction (N – W); hypoxia with ad lib drinking water (H + W); and hypoxia with water restriction (H – W). At the end of 24 h, a 15 mL/kg arterial haemorrhage was performed.

3. Water restricted rats had elevated pre‐haemorrhage vasopressin levels. Haemorrhage induced an increase in vasopressin in all groups. Water restriction (N – W) or hypoxia (H + W) each augmented the vasopressin response to haemorrhage. However, the combination of hypoxia and water restriction (H – W) failed to augment the vasopressin response to haemorrhage as compared to normoxic, water replete (N + W) rats.

4. Hypoxia or water restriction per se augment the vasopressin response to haemorrhage. This augmented vasopressin response to haemorrhage is not maintained when hypoxia and water restriction are combined.