bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathological responses of rat skeletal muscle to a single subcutaneous injection of a toxin isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus
Authors: Harris J. B. , Johnson Margaret A. , Karlsson E.
Published: June 2007

1. The pathology of mammalian skeletal muscle following a single subcutaneous injection of a purified toxin from the venom of the Australian tiger snake, Notechis scutatus scutatus, has been investigated.

2. The toxin was injected into the antero‐lateral aspect of one hind limb of rats and the effects of the injection on the histology, histo‐chemistry and physiology of the extensor digitorum longus muscles were studied.

3. The muscles underwent degenerative necrosis, with oedema and the infiltration of lymphocytes, polymorphs and macrophages within 12–24 h after the injection.

4. Three days after injection, the oedema had subsided and the necrotic fibres had been completely destroyed by phagocytes. Small uninucleate cells, with basophilic cytoplasm and vesicular nuclei were present at this stage; on the basis of these criteria they were identified as regenerating myoblasts.

5. By 5 days the myoblasts had fused to form myotubes, but differentiation of the myotubes into histochemically distinct muscle fibre types did not commence until around 7 days after the injection.

6. Regeneration and differentiation was virtually complete by 21 days after injection.

7. Between 3 and 5 days, many of the fibres were sensitive to acetylcholine, and muscle fibre action potentials were resistant to tetrodotoxin. Miniature end‐plate potentials were of low amplitude and frequency; they may have been absent from many fibres.

8. By 7–10 days, the proportion of fibres with tetrodotoxin‐resistant action potentials was declining, and acetylcholine sensitivity was less marked; miniature end‐plate potentials, though of normal amplitude, were of reduced frequency. The fibres were virtually normal by 14–21 days.

9. It is considered likely that these physiological properties were recorded from regenerating muscle fibres that reached maturity by 28 days; the possibility that they were recorded from functionally denervated fibres is discussed.

10. The rapid rate of regeneration and differentiation of the toxin‐damaged muscle was sustained only if the peripheral nerve supply was left intact.

11. Preliminary results suggested that mitochondria‐rich fibres were preferentially damaged by the toxin, and that the toxin is less active in vitro than in vivo. These problems are currently being investigated.

12. It is concluded that the toxin has a direct myotoxic effect on muscles; the relationship of this effect to the previously described neurotoxic effect is also currently under investigation.
Hexoprenaline: β‐adrenoreceptor selectivity in isolated tissues from the guinea‐pig
Authors: O'Donnell Stella R. , Wanstall Janet C.
Published: June 2007

1. A catecholamine β‐adrenoreceptor agonist, hexoprenaline, was examined in vitro on five guinea‐pig tissues and its potency relative to isoprenaline (as 100) obtained.

2. Hexoprenaline clearly delineated between those tissues classified as containing β2‐adrenoreceptors (trachea, hind limb blood vessels and uterus; relative potencies 219, 110 and 76 respectively) and those classified as containing β1‐adrenoreceptors (atria and ileum; relative potencies 3·3 and 1·0 respectively).

3. Hexoprenaline differed from some previously studied noncatecholamine β‐adrenoreceptor agonists in being only two‐fold less potent, relative to isoprenaline, as a vasodilator in perfused hind limb than as a tracheal relaxant.
PERMEABILITY AND PORE RADII OF PULMONARY CAPILLARIES IN RABBITS OF DIFFERENT AGES
Authors: Perry M. A. , Garlick D. G.
Published: June 2007

1. The double indicator diffusion technique was used to determine pulmonary capillary permeability in rabbits of different ages. Diffusible molecules ranging in size from mannitol to inulin were used in pairs, together with a vascular tracer.

2. The extraction of diffusible molecules in successive venous samples showed a rapid decline with time. The extraction at appearance time of the tracers in the venous samples was used to determine a permeability ratio for pairs of diffusible molecules.

3. Pore radii and slit widths were calculated from permeability ratios by a new application of existing equations. Because the permeability ratios were similar to the ratio of the free diffusion coefficients of the diffusible molecules in all but foetal animals, the upper 95% confidence limit of the permeability ratio was used to determine the lower 95% confidence limit of pore radius in each age group. The lower limit of pore radius ranged between 7.1 nm and 25.0 nm for neonatal and older rabbits, while foetal animals showed a range of 2.7 nm to 8.3 nm.

4. The PAm for inulin and lower limit of pore radius were used to estimate pore area and pore number per cm2 capillary surface area. The pore area per cm2 capillary surface area ranged between 1.58 × 10‐4 cm2 (neonate) to 0.45 × 10‐4 cm2 (adult). These values are similar to other estimates for pore area in skeletal muscle capillaries. The corresponding values for pore number were 9.99 × 107 (neonate) and 0.52 × 107 (adult) per cm2 capillary surface area, values which are one‐tenth to one‐hundredth the estimates for pore number in skeletal muscle capillaries.

5. The smaller number of large pores in the pulmonary capillaries of the adult rabbit would confer on this organ a six‐fold greater filtration‐reabsorption capacity per unit surface area, while diffusional exchange would be reduced to one‐half that seen in skeletal muscle capillaries.
INHIBITION OF HUMAN PULMONARY PHOSPHODIESTERASE ACTIVITY BY THERAPEUTIC LEVELS OF THEOPHYLLINE
Authors: Poison J. B. , Krzanowski J. J. , Goldman A. L. , Szentivanyi A.
Published: June 2007

1. To test the hypothesis that inhibition of cyclic nucleotide phosphodiesterase is the major mechanism of the bronchodilator action of theophylline in reversible airways disease, the effects of therapeutic plasma levels of the drug on human pulmonary phosphodiesterase activity were examined.

2. Therapeutic levels of theophylline inhibited the phosphodiesterase‐catalysed hydrolysis of adenosine cyclic 3′,5′‐monophosphate (cAMP) and guanosine cyclic 3′,5′‐monophosphate (cGMP), but the percentage inhibition was relatively small.

3. The results, while supporting the assumed contribution of phosphodiesterase inhibition to the overall mechanism of theophylline action, suggest that other presently unknown factors must also be taken into consideration to fully explain the beneficial effects of theophylline in reversible airways disease.
FURTHER OBSERVATIONS ON THE PATHOLOGICAL RESPONSES OF RAT SKELETAL MUSCLE TO TOXINS ISOLATED FROM THE VENOM OF THE AUSTRALIAN TIGER SNAKE, NOTECHIS SCUTATUS SCUTATUS
Authors: Harris J. B. , Johnson Margaret A.
Published: June 2007

1. Some aspects of the response of mammalian skeletal muscle following the injection of purified toxins from the venom of the Australian tiger snake, Notechis scutatus scutatus, are described.

2. The toxins used were notexin, notechis II‐5, notechis II‐1 and a modified form of notexin (PBP‐notexin). They were injected into the dorso‐lateral aspect of one hind limb so that the soleus muscle would be exposed to the toxins.

3. Within 1 h after the injection of notexin, the soleus muscles were oedematous and by 3–6 h, polymorphonuclear leucocytes had entered the interstitial spaces. The invasion of necrotic muscle fibres was extensive by this time. Muscle spindles appeared relatively unaffected by the toxin.

4. The muscle regenerated via myoblasts at 2–3 days to myotubes at 3–5 days, immature muscle fibres at 7–14 days and fully differentiated muscle fibres by 21–28 days. Even after 6 months, however, the nuclei of many muscle fibres remained in a central position.

5. A second component of Australian tiger snake venom was also found to be myotoxic. It was slightly less potent than notexin, but caused qualitatively similar damage to that caused by notexin. It was identified as notechis II‐5. A third fraction, notechis II‐l, was found to be inactive.

6. Notexin could be neutralized by incubation with tiger snake antivenene; the simultaneous injection of antivenene with notexin did not afford complete protection against muscle damage.
THE EFFECT OF SOME CENTRALLY ACTIVE DRUGS ON CORTICOSTERONE SECRETION AND METABOLISM IN RATS
Authors: Chan Mo Yin , Holmes W. N.
Published: June 2007

1. Male rats were treated with morphine sulphate (10 mg/kg), methadone (10 mg/kg) and chlorpromazine (8.0 mg/kg) respectively, for 2 weeks.

2. At the end of this period, the adrenal glands of treated rats had increased in weight.

3. The concentration of corticosterone in the peripheral plasma was significantly lowered in the chlorpromazine‐treated rats, increased in the methadone‐treated rats and was unchanged in the morphine‐treated rats.

4. The metabolic clearance rate of [1,2‐3H]corticosterone decreased in the chlorpromazine‐treated rats, while only a slight reduction was observed with methadone treatment.

5. These results showed that chronic treatment with either morphine or methadone did not suppress the adrenal function. The possible site of action of chlorpromazine in suppressing corticosterone secretion is discussed.
THE CONTRACTILE RESPONSE OF SMOOTH MUSCLE TO IMMERSION IN HYPERTONIC SOLUTIONS
Authors: Kirkpatrick C. T. , Morrow R. J. , Tomita T.
Published: June 2007

1. Strips of bovine tracheal muscle and rabbit aorta produced sustained contractions on perfusion with Krebs solution made twice normal strength by addition of sucrose. The contractures were relaxed on return to normal Krebs solution.

2. Similar contractures were produced by tracheal muscle strips in Krebs solutions made twice normal strength by addition of galactose, glucose or NaCl whereas urea caused only a transient contraction.

3. In twice normal strength Krebs solution (sucrose added) the basal tension of rat portal vein and guinea‐pig taenia coli was increased. Spontaneous mechanical activity was maintained, but the frequency of contractions was reduced.

4. The hypertonic contracture of bovine trachea in twice normal strength Krebs solution (sucrose added) was reduced by 15% by omission of Ca from the bathing fluid (01 mmol/1 EGTA added). Severe Ca depeletion, by prolonged washing in Ca‐free Krebs with 12.5 mmol/1 EGTA and Carbachol added, resulted in a 77% reduction in the hypertonic contracture.

5. In twice normal Krebs solution (sucrose added), the hypertonic contracture was partially relaxed by isoprenaline (4 × 10−6 mol/1); the contractile response to carbachol was reduced; the contractile response to high‐K Krebs solution was maintained.

6. Atropine (5 × 10−7 mol/1) abolished the contractile response to carbachol, but had no effect on the hypertonic contracture.

7. It is suggested that the contraction of bovine tracheal strips in hypertonic solutions is mainly due to activation of the contractile myofilaments rather than simple cell shrinkage. Hypertonic solutions may also interfere with some steps in the excitation‐contraction coupling sequence.
ANGIOTENSIN CONVERTING ENZYME IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Mendelsohn F. A. O. , Hutchinson J. S. , Csicsmann J.
Published: June 2007

1. Angiotensin converting enzyme (ACE) was measured in homogenates of regions of rat brain using the substrate Hip‐His‐Leu.

2. The enzyme resembled classical ACE in its marked CI” dependence and inhibition by both SQ 20,881 (25 μmol/1) and EDTA (1 mmol/1).

3. Spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto controls (NT‐WK) were killed at 20‐22 weeks of age and their brains dissected into eight regions.

4. There were marked region variations of ACE with highest levels in striatum, hippocampus, cerebellum and pituitary and lower levels in hypothalamus and cerebral cortex.

5. In three brain regions ACE was significantly lower in SHR compared to NT‐WK: medulla oblongata (P<0.05), hypothalamus (P<0‐02) and cerebral cortex (P < 005). In the other sites the levels were not different.

6. These region‐specific differences of ACE in the SHR could lead to altered production or metabolism of central neuropeptides postulated to be involved in the control of blood pressure.
EFFECTS OF GOLD SODIUM THIOMALATE ON CYTOSOLIC COPPER AND ZINC IN THE RAT KIDNEY AND LIVER TISSUES
Authors: Sharma R. P. , McQueen E. G.
Published: June 2007

1. Male Wistar rats were given a single subcutaneous injection of gold sodium thiomalate and killed 7 days later. The binding of Au, Zn and Cu to the kidney and liver cytosolic proteins of control and gold‐treated rats was determined.

2. In the renal cytosol of Au(I)‐ exposed rats, the binding of Cu to the low‐molecular‐weight (LMW) proteins increased by 62%, and to the high‐molecular‐weight (HMW) proteins the binding decreased by 54%. The incorporation of Cu into the liver cytosolic proteins increased, in both, the HMW and the LMW proteins. The binding of Zn into the renal cytosolic proteins was increased by 39% (HMW proteins) and 100% (LMW proteins). Au(I) had little effect on the binding of Zn to the cytosolic proteins in the liver.

3. It is suggested that the therapeutic action of gold complexes may be mediated, to some extent, by its effects on the metabolism of Cu and/or Zn.
POSSIBLE MEDIATORS OF THE WRITHING RESPONSE INDUCED BY ACETIC ACID OR PHENYLBENZOQUINONE IN MICE
Authors: Baird‐Lambert J. , Jamieson D. D.
Published: June 2007

Despite widespread use of the writhing response to phenylbenzoquinone or acetic acid injection in mice as a screen for analgesic activity, possible mediators of this response remain unidentified.

In the present experiments both in vivo and in vitro techniques have been used in an attempt to identify these mediators.

Acetic acid‐induced writhing was unaffected by pretreatment with mepyramine, methysergide, disodium cromoglycate or cimetidine.

Phenylbenzoquinone‐induced writhing was partially blocked by pretreatment with mepyramine or other antihistamines.

Using guinea‐pig isolated ileum and rat fundus preparations as in vitro assay systems, no significant differences were detected in histamine, serotonin, or prostaglandin content of peritoneal fluid from writhing and control mice.

Acetylcholine levels were at the limit of detection in these samples, and there was no evidence of kinin release.

Thus the mediators involved in the writhing response remain undefined.
IS FLEMING'S LYSOZYME AN ANALGESIC AGENT? EXPERIMENTS ON MICE
Authors: Bianchi Camillo
Published: June 2007

Antinociceptive activity of hen egg white lysozyme (Fleming's lysozyme) was determined against abdominal contractions provoked by irritants injected in‐traperitoneally into mice. Carrageenan (2 mg) (CA) injected with arachidonic acid (15 μg) (AA) or prostaglandins PGE1 or PGF2α (0.04 ng), brewer's yeast (10 mg), caolin (10 mg), mepartricin (80 U) and phenylquinone (50 μg) were used as irritants.

2 Lysozyme was active at 400‐800 mg/kg i.v. against CA + AA, CA + PG, brewer's yeast and caolin nociceptive stimulation. The compound was more effective against CA + AA than against CA + PG. Acetylsalicylic acid at 50‐100‐200 mg/kg p.o. was equally active against CA + AA and CA + PG.

3 Lysozyme was inactive in the tail pinch and hot plate tests that mainly detect central analgesics.

4 The results are discussed in relation to the claim advanced years ago that lysozyme is an effective analgesic agent in humans. The compound was found active against herpes zoster or cancer pain but did not find use despite the favourable reports presented.

5 The experimental results obtained on laboratory animals do not contradict the conclusions drawn after the clinical use of the compound.
SALT AND WATER INTAKE AND SODIUM AND POTASSIUM EXCRETION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: May C. N. , Parsons B. J.
Published: June 2007

Total fluid and saline intakes were greater in spontaneously hypertensive rats (SHR) than in normotensive rats (NTR).

Total fluid and saline intake were significantly elevated in prehypertensive SHR, 5 weeks old, compared with age‐matched NTR, and the intakes fell with age in both strains but remained considerably greater in SHR.

In SHR, in which the blood pressure was maintained at normotensive levels by treatment with hydralazine, the saline and fluid intakes remained elevated above those of NTR.

SHR and NTR fed low sodium diet with water alone to drink have similar excretion rates of sodium, suggesting that their ability to conserve sodium was normal.

Measurement of sodium excretion after three different levels of sodium loading, on normal or low sodium diets, also failed to demonstrate an abnormality of renal function in SHR.

These results demonstrate that the fluid and saline intakes of SHR are elevated compared with NTR and this difference is independent of the hypertension in SHR and is not secondary to enhanced renal sodium loss.
DEPENDENCE OF β‐ADRENERGIC RESPONSIVENESS ON THYROID STATE OF MALE RATS
Authors: Threatte R. M. , Barney C. C. , Baker S. P. , Fregly M. J.
Published: June 2007

1 The dose of thyroxine (0‐150 μg/kg body weight) administered subcutaneously daily to surgically thyroidectomized male rats was correlated significantly with their metabolic activity as assessed by rate of oxygen consumption and colonic temperature.

2 There was a significant dose‐dependent increase in total serum thyroxine, triiodothyronine and reverse‐triiodothyronine concentrations with increasing doses of thyroxine administered.

3 The cardiostimulatory response to administration of isoprenaline (8 μg/kg body weight s.c.) was also correlated directly with the dose of thyroxine administered.

4 The concentration of cardiac β‐adrenoceptors in these animals was correlated significantly with total serum thyroxine and triiodothyronine concentrations, basal heart rate, and the chronotropic response to administration of isoprenaline.
INFLUENCE OF EXTRA‐INTESTINAL INFLAMMATION ON THE IN VITRO ABSORPTION OF 14C‐GLUCOSE AND THE EFFECTS OF ANTIINFLAMMATORY DRUGS IN THE JEJUNUM OF RATS
Authors: Somasundaram S. , Sadique J. , Subramoniam A.
Published: June 2007

Inflammation was induced in the hind legs of rats by formalin injection and the in vitro jejunal absorption of 14C‐glucose was studied.

Treatment of rats with formalin caused a reduction in the in vitro absorption of glucose from the jejunum.

Oral administration of oxyphenbutazone or a herbal anti‐inflammatory drug (Withania somnifera) prior to formalin injection, resulted in no alteration in the jejunal absorption of glucose.
A PRELIMINARY STUDY ON PAIN PERCEPTION AND TOBACCO SMOKING
Authors: Milgrom‐Friedman Jeanette , Penman Robyn , Meares Russell
Published: June 2007

1. Ischaemic pain onset and tolerance in response to a pneumatic blood pressure cuff were compared in 17 non‐deprived smokers, 30 deprived smokers, 15 smokers chewing nicotine gum and 16 non‐smokers.

2. Following removal of the cuff, all subjects completed the McGill pain questionnaire, rating pain in terms of its sensory, affective, evaluative and miscellaneous qualities.

3. Group differences were found in the time elapsing before reporting the first twinge of pain. Non‐deprived smokers had the shortest period to onset of pain. The longer the smokers had been deprived of cigarettes, the longer before the onset of pain.

4. Non‐deprived smokers also had a significantly shorter period of pain tolerance compared to deprived smokers.

5. Non‐deprived smokers tended to have a faster pain onset and a shorter tolerance period compared to non‐smokers.

6. Smokers’ indices of pain were significantly higher on the several sub‐scales describing the qualitative pain experience compared to non‐smokers and to smokers deprived of cigarettes for more than one hour.

7. Deprivation of cigarettes appears to diminish smokers’ sensitivity to pain significantly below that of non‐smokers and smoking cigarettes tends to heighten sensitivity to, or beyond, the level of non‐smokers.
EFFECTS OF A NON‐VASOCONSTRICTOR DOSE OF PHENYLEPHRINE ON PROSTAGLANDIN E2 AND RENIN RELEASE IN ANAESTHETIZED DOGS
Authors: Hisa H. , Satoh S.
Published: June 2007

Phenylephrine (1 μg/min) was infused into the renal artery of pentobarbitone anaesthetized dogs. Systemic blood pressure and renal blood flow were monitored. Arterial and renal venous blood samples were collected before and 10 min after the start of the infusion. Plasma prostaglandin E2 concentration and plasma renin activity were measured by radioimmunoassay.

This dose of phenylephrine did not affect systemic blood pressure and renal blood flow.

However, both prostaglandin E2 and renin secretion rates were increased by the infusion of phenylephrine.

These results suggest that renal α‐adrenoceptors participate in prostaglandin and renin release independent of the changes in systemic blood pressure and renal blood flow.
HAEMODYNAMIC EFFECTS OF PRENALTEROL IN ACUTE MYOCARDIAL ISCHAEMIA IN OPEN CHEST PIGS
Authors: Branzi A. , Binetti G. , Specchia S. , Hi C. Mage , Zannoli R. , Magnani B.
Published: June 2007

1. The haemodynamic effects of prenalterol, a new sympathomimetic agent, have been studied in anaesthetized open‐chest pigs with acute myocardial ischaemia provoked by left anterior descending coronary artery ligation. A group of eight animals was infused with saline and served as control (C).

2. In both groups the ligation of the left anterior descending coronary artery determined a significant (P<0.05) reduction of aortic flow, maximum left ventricular (LV) dp/dt with no changes in heart rate.

3. The infusion of a first dose of 30 m̈g/kg of prenalterol restored the depressed haemodynamics but increased significantly the heart rate in the prenalterol group while the saline infused group did not show any significant changes. The haemodynamic effects of prenalterol were still evident 25 min after the infusion.

4. The subsequent administration of a second dose of 60 m̈g/kg of prenalterol resulted in a further improvement of the aortic flow, LV dp/dt and heart rate which reached values higher than in the basal condition.

5. The positive inotropic effect was not associated with changes in stroke volume, therefore the increase in aortic flow was essentially due to an increase of the heart rate.

6. It is concluded that prenalterol is a powerful inotropic agent in acutely infarcted animals. Its action on aortic flow appears to be related to an increase in heart rate in contrast to some previous observations.
ENDOGENOUS VASOPRESSIN MODULATES THE BAROREFLEX SENSITIVITY IN RATS
Authors: Imai Yutaka , Nolan Peter L. , Johnston Colin I.
Published: June 2007

1. The effect of endogenous vasopressin on the baroreceptor reflex has been examined by comparing baroreflex function in Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI rat) with that in Long‐Evans rats (LE rat).

2. Baroreflex function was assessed in conscious unrestrained rats during increases in blood pressure with phenylephrine.

3. The slope of the baroreflex function line in LE rats [(19.0, s.e.m. = 1.4) × 10‐4, n = 34] was significantly steeper than that in DI rats [(6.9, s.e.m. = 0.6) × 10‐4, n = 44, P< 0.0001].

4. A subpressor infusion of arginine8‐vasopressin (2 ng/kg per min for 2 h i.v.) and an equidose of DDAVP caused bradycardia and increased the baroreflex function slope significantly.

5. Acute volume expansion in DI rat did not change the baroreflex sensitivity.

6. A specific vasopressin vascular receptor antagonist, d(Ch2)5Tyr(Me)AVP, did not alter the baroreflex sensitivity in LE rats.

7. These results suggest that endogenous vasopressin is an important physiological regulator of the baroreflex sensitivity in normal rats.
INTENSE VASOCONSTRICTION AND BRADYCARDIA EVOKED BY STIMULATION OF NEURONES WITHIN THE MIDBRAIN VENTRAL TEGMENTUM OF THE RABBIT
Authors: Tan Esther , Goodchild A. K. , Dampney R. A. L.
Published: June 2007

1. Electrical stimulation of sites in the midbrain ventral tegmental area (VTA) and the lateral hypothalamic area of the anaesthetized rabbit elicited intense vasoconstriction and profound bradycardia.

2. The same effects were elicited by microinjections of glutamate ions into the VTA but not the lateral hypothalamic area.

3. Following baroreceptor denervation, the bradycardic component of the response was greatly reduced, but the vasoconstrictor component was unaffected.

4. It is concluded that the cardiovascular response is generated by excitation of a cell group within the VTA, but within the hypothalamus the response arises from excitation of axons of passage.
THE EFFECT OF THE CALCIUM ION ANTAGONIST 8‐(N,N‐DIETHYLAMINO)‐OCTYL‐3,4,5‐TRIMETHOXYBENZOATEON MALIGNANT HYPERPYREXIA‐SUSCEPTIBLE PORCINE SKELETAL MUSCLE
Authors: Sullivan J. S. , Galloway G. J. , Denborough M. A.
Published: June 2007

1. In malignant hyperpyrexia susceptible (MHS) porcine skeletal muscle, a low concentration (100 μmol/1) of the calcium ion antagonist 8‐(N,N‐diethyl‐amino)‐octyl‐3,4,5‐trimethoxybenzoate (TMB‐8) inhibited KCl‐induced contractures, but potentiated contractures induced by halothane, caffeine and succinylcholine.

2. Higher concentrations of TMB‐8 (333 μmol/1 to 1 mmol/1) contracted MHS muscle, but had little effect on muscle tension in control preparations.

3. Treatments which inhibit excitation‐contraction coupling abolished TMB‐8‐induced hyper‐reactivity in MHS muscle.

4. TMB‐8 (50 μmol/1 and 1 mmol/1) did not alter 45Ca2+ levels in actively loaded microsomal preparations from MHS swine.

5. These results suggest that in malignant hyperpyrexia the primary abnormality occurs proximal to the release of calcium from the sarcoplasmic reticulum, probably at the level of excitation‐contraction coupling.
QUANTITATIVE STRUCTURE‐ACTIVITY RELATIONSHIPS OF IMIDAZOLIDINE DERIVATIVES RELATED TO CLONIDINE AT PERIPHERAL α‐ADRENOCEPTORS
Authors: Medgett I. C. , McCulloch M. W.
Published: June 2007

1. The effects of clonidine, oxymetazoline and thirteen substituted phenyl‐iminoimidazolidine analogues of clonidine were studied and compared on postjunctional α‐adrenoceptors in guinea‐pig and rabbit aorta and on prejunctional α‐adrenoceptors in guinea‐pig atria.

2. In the aorta all compounds were partial agonists at postjunctional α‐adrenoceptors. Correlation of agonist potency with various combinations of their physicochemical parameters showed that, with the present series of compounds, physicochemical parameters alone determined 92% of the variance in the data with potency being primarily and highly correlated with pKa.

3. Similarly in atria, all compounds, with the possible exceptions of St 95 and St 1943, appeared to be partial agonists at prejunctional α‐adrenoceptors; transmitter noradrenaline release could either be inhibited (field stimulation at 1 Hz for 5 s) or enhanced (5 Hz for 30 s).

4. The results indicate that 2,6‐substitution in the phenyl ring appears to be a specific non‐physicochemical activity‐enhancing factor at prejunctional but not postjunctional α‐adrenoceptors.

5. A comparison with data in the literature giving the acute hypotensive potencies of the compounds suggests that central α‐adrenoceptors may more closely resemble atrial prejunctional α‐adrenoceptors than aortic postjunctional α‐adrenoceptors.

6. Quantitative correlations between centrally‐mediated hypotensive and peripheral vasoconstrictor effects of clonidine‐like imidazolidines do not provide a sufficiently sensitive method of distinguishing between a‐adrenoceptor subtypes.
EFFECTS OF ADRENALECTOMY AND ADRENAL STEROIDS ON THE UPTAKE OF SEROTONIN IN RAT PLATELETS
Authors: Lee P. H. K. , Chan Mo‐Yin
Published: June 2007

1. Changes induced by adrenalectomy, triamcinolone treatment and deoxycorticosterone (DOC) treatment on the uptake of [3H]‐serotonin into platelets were studied ex vivo, using rat platelets suspended in physiological medium.

2. Adrenalectomy caused a decrease in active uptake of serotonin and an associated increase in apparent Km.

3. Treatment of the adrenalectomized rats with triamcinolone (0.25 mg/kg), but not DOC (1.0 mg/kg) restored the active uptake of serotonin.

4. At triamcinolone dose of 0.5 mg/kg, the serotonin uptake was raised to a level that was significantly higher than normal.

5. Kinetic analysis of uptake data showed the apparent Km, to be affected by both triamcinolone and DOC, while the apparent Vmax of uptake rate was increased by triamcinolone treatment.
SUPINE HYPERTENSION, BLOOD PRESSURE VARIABILITY AND CIRCADIAN RHYTHM IN AUTONOMIC FAILURE: THE ROLE OF AMBULATORY INTRA‐ARTERIAL MONITORING
Authors: Mann Stewart , Bellamy G. R. , Hunyor S. N. , Raftery E. B. , Ingall T. , Bannister R.
Published: June 2007

1. Blood pressure variation over 24 h was studied in twelve subjects with suspected or established autonomic failure using ambulatory intra‐arterial monitoring.

2. Three subjects who had been previously diagnosed as having orthostatic hypotension due to autonomic failure were found to have normal circulatory reflexes.

3. A generally consistent circadian variation of blood pressure was seen in the other nine subjects, pressure rising gradually from its lowest point early in the morning to a peak during the early part of the night; this pattern was also found during bed rest in four subjects.

4. Supine hypertension (an hourly mean blood presure of > 170/90 mmHg) not suspected from sphygmomanometric readings was observed in four subjects, generally during the night.

5. Heart rate variability was reduced in six subjects while short‐term blood pressure variability was markedly increased.
ANGIOTENSIN CONVERTING ENZYME DURING ACUTE AND CHRONIC ENALAPRIL THERAPY IN ESSENTIAL HYPERTENSION
Authors: Jackson B. , Johnstoa C. I.
Published: June 2007

1. The acute and chronic effects of enalapril (MK421) were assessed in a double‐blind randomized trial in subjects with essential hypertension.

2. In acute studies, twelve subjects received enalapril (10 mg p.o.), following which there was a fall in blood pressure, maximal at 6 h and lasting for 24 h. Serum MK422 (enalaprilic acid, the bioactive form of enalapril) and serum angiotensin converting enzyme (ACE) inhibition had a similar time course with good correlation between drug levels and ACE inhibition (P<0.001, r= 0.98, n= 16) and between ACE inhibition and the hypotensive effect (P<0.001, r= 0.84, n= 16).

3. In chronic studies enalapril was titrated from 5 mg to 20 mg twice a day in eleven hypertensive patients to achieve a diastolic blood pressure <90 mmHg. Treatment continued for 3–12 months. Increasing serum MK422 was correlated with reducing serum ACE activity (P<0.001, r= 0.45, n= 104). The fall in blood pressure correlated both with serum MK422 level (P < 0.05, r= 0.37, n= 39) as well as ACE inhibition (P < 0.01, r= 0.45, n= 42).

4. The drug level:ACE inhibition curve was shifted to the right during chronic enalapril treatment. ID50 for serum ACE was 32 ng MK422/ml following the single 10 mg dose of MK421 and 70 ng MK422/ml during chronic treatment. Blood pressure falls during acute and chronic treatment were similar over the range of serum MK422 levels achieved.

5. The shift in the drug level:ACE inhibition curve suggests induction of ACE during chronic treatment with enalapril in man.
HAEMODYNAMIC AND NEUROENDOCRINE CONSEQUENCES OF STOPPING SMOKING‐A CONTROLLED STUDY
Authors: Puddey I. B. , Vandongen R. , Beilin L. J. , English D.
Published: June 2007

1. The haemodynamic and neuroendocrine consequences of stopping smoking for a 6 week period were studied in thirty‐three smokers and their matched controls.

2. Complete smoking cessation was associated with a significant fall in adrenaline and cortisol levels, consistent with the withdrawal of a nicotine stimulus to adrenomedullary and cortical activity.

3. Supine systolic and diastolic blood pressure did not change significantly. However, the response to a cold pressor stimulus was altered with a delay in return of systolic blood pressure to basal values.

4. This study has been unable to confirm findings from epidemiological studies of lower blood pressure in smokers. However, the possibility is raised that this phenomenon may be due to modification by smoking of the normal physiological response to stressful stimuli.
LESIONS OF THE VENTROLATERAL MEDULLA IN NORMAL AND VASOPRESSIN‐DEFICIENT (BRATTLEBORO) RATS
Authors: Minson J. B. , Chalmers J. P.
Published: June 2007

1. The cardiovascular response to electrolytic lesions of the A1 noradrenaline cell group (A1 lesion) were studied in the rat.

2. A1 lesions in normal rats cause acute hypertension and bradycardia and elevate plasma arginine‐vasopressin (AVP), as previously described in the rabbit.

3. After A1 lesions in vasopressin deficient rats the hypertension is not reduced compared to that seen in normal rats, but the bradycardia is attenuated.

4. AVP makes a greater contribution to the bradycardia than to the hypertension after A1 lesions.
PLASMA ALDOSTERONE LEVELS AFTER KCI LOADING IN RATS ADAPTED TO A HIGH POTASSIUM DIET
Authors: Adam William R. , Campbell Duncan J.
Published: June 2007

1. Plasma levels of aldosterone, corticosterone, potassium and renin activity, and urinary potassium excretion, were measured in control (CK) rats, and in rats adapted to a high potassium diet (HK), before and after an acute intragastric KCl load.

2. Prior to the KCl load there was no difference in plasma potassium (K) or plasma aldosterone.

3. Following the KCl load, HK rats maintained a lower plasma K, and, except at 30 min after the load, a lower plasma aldosterone than CK rats.

4. At a low plasma K there was no difference in plasma aldosterone between CK and HK rats. At a high plasma K (>8 mmol/l) the HK rats had a higher plasma aldosterone for the same plasma K than CK rats.

5. The enhanced ability to excrete an acute K load seen in HK rats seems unlikely to be due to higher levels of plasma aldosterone.
A COMPARISON OF THE HAEMODYNAMIC EFFECTS OF DIETARY SODIUM RESTRICTION AND ACUTE SODIUM DEPLETION IN THE CONSCIOUS SHEEP
Authors: Mason R. T. , Coghlan J. P. , Denton D. A. , Fei D. W. T. , Scoggins B. A. , Stewart K. W. , Whitworth J. A.
Published: June 2007

1. The use of a low Na, low K sorghum grain diet supplemented with intraruminal electrolyte infusions has enabled dietary manipulation of sodium status to be studied in the sheep.

2. Dietary sodium restriction reduced urinary sodium excretion within 24 h with maximal retention after 3 days. There were no other substantial metabolic or haemodynamic changes.

3. A more severe form of sodium deficiency produced by parotid salivary drainage resulted after only 2 days in a sodium deficit 3–4 times that seen with 14 days of sodium restriction. Extracellular fluid volume and cardiac output decreased. Blood pressure was unchanged but there was an increase in peripheral resistance and plasma renin concentration.
6‐KETO‐PROSTAGLANDIN E1 AND PROSTAGLANDIN E2 STIMULATE ALDOSTERONE PRODUCTION IN BOVINE ADRENAL GLANDS
Authors: Tsunoda S. , Demura R. , Demura H.
Published: June 2007

1. In order to investigate the effect of prostaglandins on aldosterone synthesis, dispersed bovine adrenal cells were incubated with prostaglandins and the aldosterone concentration was measured by radioimmunoassay.

2. The result was that aldosterone production was stimulated by 6‐keto‐prostaglandin E1 and prostaglandin E2.
CIRCULATING LEVELS OF ARGININE VASOPRESSIN BEFORE AND DURING THE INFUSION OF THE HORMONE IN PATIENTS PRESENTING WITH BLEEDING OESOPHAGEAL VARICES
Authors: Jenkins S. A. , Devitt P. , Baxter J. N. , Shields R.
Published: June 2007

1. Circulating levels of antidiuretic hormone (ADH) were measured in patients presenting with bleeding oesophageal varices before and during treatment with arginine vasopressin.

2. There was no significant difference in the circulating levels of ADH before and during treatment with arginine vasopressin in patients in which the hormone successfully controlled haemorrhage and those in which it did not.

3. It is concluded that the failure of vasopressin to control variceal haemorrhage in approximately 40% of patients presenting for treatment cannot be attributed to higher circulating levels of the hormone in these subjects.
A DOUBLE‐BLIND CONTROLLED CLINICAL TRIAL OF MASTIC AND PLACEBO IN THE TREATMENT OF DUODENAL ULCER
Authors: Al‐Habbal Mohammad Jamil , Al‐Habbal Zakaria , Huwez Farhad Umer
Published: June 2007

1. A double‐blind clinical trial was carried out on thirty‐eight patients with symptomatic and endoscopically proven duodenal ulcer to compare the therapeutic responses to mastic (1 g daily, twenty patients) and placebo (lactose, 1 g daily, eighteen patients) given orally over a period of 2 weeks.

2. Symptomatic relief was obtained in sixteen (80%) patients on mastic and in nine (50%) patients on placebo, while endoscopically proven healing occurred in fourteen (70%) patients on mastic and four (22%) patients on placebo. The differences between treatments were highly significant (P<0.01). Mastic was well tolerated and did not produce side effects.

3. It is concluded that mastic has an ulcer healing effect, but further studies are needed to establish its role in treating peptic ulcer.
EFFECTS OF CA2+ ANTAGONISTS ON CARDIOVASCULAR RESPONSES TO POSTERIOR HYPOTHALAMIC STIMULATION IN THE RAT
Authors: Eferakeya Adego E. , Osunkwo Uche A.
Published: June 2007

1. The effects of methoxyverapamil or hydralazine on pressor responses to posterior hypothalamic stimulation and injected pressor agents were studied in normotensive male Wistar rats.

2. Methoxyverapamil inhibited both phases of pressor response to hypothalamic stimulation and pressor responses to injected noradrenaline or angiotensin II.

3. Hydralazine inhibited the secondary phase (due to adrenomedullary catecholamine) and not the primary phase (due to increased sympathetic vasomotor activity) of pressor response to hypothalamic stimulation. However, it inhibited the pressor responses to exogenous noradrenaline or angiotensin II.

4. The data indicate that hydralazine is ineffective in inhibiting the pressor response elicited by noradrenaline endogenously released at the sympathetic nerve endings.
DEMONSTRATION OF α‐ADRENOCEPTOR ANTAGONISM BY THE 5HT2 ANTAGONIST, KETANSERIN (R49945), IN SHEEP
Authors: Nelson M. A. , Coghlan J. P. , Denton D. A. , Mills E. H. , Spence C. D. , Whitworth J. A. , Scoggins B. A.
Published: June 2007

1. Serotonin causes a dose related (0.1–20 μg/kg i.v.) increase in mean arterial blood pressure (MAP) and heart rate in conscious sheep.

2. Ketanserin (0.1 mg/kg per h i.v.) causes a decrease in blood pressure, and an increase in heart rate. In the presence of ketanserin, serotonin induced increases in MAP are attenuated, or abolished, but the increases in heart rate are enhanced.

3. Ketanserin (10 mg/kg per h i.v.) attenuates or abolishes the increase in blood pressure induced by the α‐adrenoceptor agonist phenylephrine in conscious sheep. When administered in the presence of the α‐adrenoceptor antagonist prazosin, ketanserin (0.1 mg/kg per h i.v.) fails to induce a further hypotensive response.

4. These data suggest that in the conscious sheep ketanserin exhibits predominantly α‐adrenoceptor antagonism.
EFFECTS OF DOXAPRAM ON BODY TEMPERATURE OF THE RAT DURING RADIOFREQUENCY IRRADIATION
Authors: Jauchem James R. , Frei Melvin R. , Heinmets Ferdinand
Published: June 2007

1. Central nervous system stimulants can cause changes in body temperature and changes in susceptibility to high levels of radiofrequency radiation (RFR). In the present study, the effects of the central nervous system stimulant, doxapram, on thermal responses to 2.8 GHz pulsed RFR were examined in anaesthetized rats.

2. During intermittent exposure to an average power density of 60 mW/cm2, doxapram significantly increased the time required for temperature to return to the pre‐exposure level when irradiation was discontinued.

3. When exposure was continued until lethal temperatures resulted, doxapram administration caused no significant change in survival time when compared to saline controls. Thus, although the drug decreased thermoregulatory efficiency during intermittent exposure to RFR, no change in susceptibility to terminal RFR exposure was observed.
HISTAMINE AND CARBACHOL CONTRACTILE RESPONSES IN PROXIMAL AND DISTAL AIRWAYS OF THE RABBIT
Authors: Armour C. L. , Black J. L. , Berend N.
Published: June 2007

1. Airway preparations from the trachea, main bronchi, subsegmental bronchi and the parenchyma of rabbits were studied.

2. The proximal airways, the trachea and main bronchi, were less sensitive to histamine than the distal airways of the subsegmental bronchi and lung parenchymal strip.

3. The proximal airways were more sensitive to carbachol than the distal airways.

4. These results may assist in the interpretation of airway responses in vivo.
A STUDY OF THE ANTI‐ULCER ACTIVITY OF DIAZEPAM AND OTHER TRANQUILLOSEDATIVES IN ALBINO RATS
Authors: Gupta M. B. , Nath R. , Gupta G. P. , Bhargava K. P.
Published: June 2007

1. Anti‐ulcer and sedative effects of tranquillosedatives viz. benzodiazepines (diazepam, oxazepam and nitrazepam), barbiturate (phenobarbitone), phenothiazines (chlorpromazine, trifluoperazine and thioridazine) and butyrophenone (haloperidol) were compared in albino rats.

2. Ulceration of the glandular stomach was induced by 2 h restraint at 4°C. Sedation was measured using the rotarod test.

3. These tranquillosedatives showed dose dependent anti‐ulcer and sedative effects. The relative potency and therapeutic index (ratio between rotarod ED50 and anti‐ulcer ED50) of each drug were determined. Diazepam showed the highest therapeutic index (1.88).

4. Diazepam significantly reduced the volume of gastric secretion, raised its pH and prevented the gastric ulcer formation in pylorus ligated rats but failed to prevent the acute duodenal ulceration induced by intramuscular injection of histamine or carbachol in guinea‐pigs and rats, respectively.

5. These observations suggest that benzodiazepines (diazepam) are more suitable anti‐ulcer agents compared to barbiturate, phenothiazines and butyrophenone. The anti‐ulcer effect of diazepam is possibly due to a combination of sedative, anti‐anxiety and antisecretory actions.
EXTENDED THEORY OF THE EARLY DIFFUSION OF MULTIPLE INDICATORS: BOUNDS ON PERMEABILITY RATIOS, WITH APPLICATIONS TO INTESTINAL CAPILLARIES
Authors: Bass L. , Aisbett J.
Published: June 2007

1. The determination of ratios of capillary permeabilities to multiple indicators is secured by constructing upper bounds on effects of early back‐diffusion following a single arterial injection. The analysis does not exclude highly extracted indicators, and it allows for effects of asymmetric blood‐tissue exchange and of tissue concentration gradients.

2. The concept of flow limitation of uptake is delimited operationally.

3. It is shown how to identify effects of heterogeneity of uptake for data sets extended over large ranges of rate of blood flow.

4. These new methods are used to show, for several sets of previously published data from muscle, that back‐diffusion cannot change appreciably the permeability ratios determined previously without any quantification of back‐diffusion.

5. The main application is to data published by Perry and Granger (1981) on the permeability of cat intestinal capillaries to raffinose and inulin. The permeability ratios deduced from these data imply paradoxically restricted diffusion; it is shown that this cannot be attributed to effects of back‐diffusion, heterogeneity of extraction, or of solvent drag. It is shown that the paradox is removed if tissue‐to‐blood permeability to raffinose is at least double the blood‐to‐tissue permeability, possibly as part of the active transport of sugars from the intestinal lumen.

6. It is shown that corresponding results on permeability ratios in dog gastric capillaries are not paradoxical (against the standard of unrestricted diffusion) under symmetric permeability to raffinose.
SYSTEMIC AND REGIONAL HAEMODYNAMIC PROFILE OF CAPTOPRIL IN CONSCIOUS RABBITS WITH BILATERAL CELLOPHANE PERINEPHRITIS HYPERTENSION
Authors: Bolt Gert R. , Saxena Pramod R.
Published: June 2007

1. The radioactive microsphere technique was used to study the systemic and regional haemodynamic effects of the converting enzyme inhibitor captopril (0.1, 0.3 and 1.0 mg/kg) 10 min after intravenous administration in conscious rabbits with bilateral cellophane perinephritis hypertension, an experimental model of hypertension associated with normal plasma renin levels.

2. Captopril lowered arterial blood pressure as a result of a dose‐dependent decrease in total peripheral resistance. The fall in blood pressure was accompanied by an increase in cardiac output after the second and third dose of captopril; heart rate was not significantly altered.

3. Captopril produced a generalized peripheral vasodilatation; the changes in vascular conductance being most pronounced in the kidneys, intestines and skin which resulted in a significant increase in blood flow to these vascular beds.

4. The effective antihypertensive properties of captopril in this ‘low plasma renin’ model of hypertension and the uniform increase in vascular conductances produced by captopril, which antagonizes the generalized increase in vascular resistances that characterizes cellophane perinephritis hypertension, may indicate the involvement of an increased activity of the renin‐angiotensin system, possibly in tissues, such as the vascular wall and brain, in the maintenance of the elevated blood pressure in this hypertensive form.
EFFECT OF PROSTAGLANDIN E2 ON SERUM IRON AFTER ACUTE AND CHRONIC BLOOD LOSS
Authors: Al‐Waili Noori S. , AL‐Azzawi Hani T.
Published: June 2007

1. The effect of prostaglandin E2 on serum iron of New Zealand rabbits subjected to acute and chronic blood loss is demonstrated.

2. The results showed that acute blood loss was followed by significant elevation of serum iron when sera were tested on day three after the bleeding. With subcutaneous injection of 40μg/kg body weight of prostaglandin E2 for each 12 h of the experiment, acute blood loss was followed by a significant reduction in serum iron within the same period.

3. Similar results were obtained after chronic blood loss when subcutaneous injection of 20 μg/kg body weight of prostaglandin E2 was used for each 12 h of the experiment.

4. It could be concluded that the prostaglandin E2 causes marked lowering of serum iron following blood loss.
CORONARY AND PERIPHERAL VASCULAR RESISTANCE IN THE ANAESTHETIZED DIABETIC SHEEP
Authors: Hoffman Linda , Yong A. C. , Heath J. , Kilpatrick D.
Published: June 2007

1. To determine whether vascular resistance was altered in diabetes, the vascular resistance in both the peripheral arterial bed and the circumflex coronary artery was compared in six normal and five diabetic adult sheep, under pentobarbitone anaesthesia. Diabetes induced by alloxan significantly increased blood glucose (15.6mmol/l, s.e.m. = 2.8, vs 5.5 mmol/l, s.e.m. =0.6; P>0.001) compared with controls.

2. Systolic blood pressure was lower in diabetics (92 mmHg, s.e.m. = 12, vs 123 mmHg, s.e.m. =5; P<0.025) as was diastolic blood pressure (73 mmHg, s.e.m. = 15, vs 104 mmHg, s.e.m. =4; P > 0.05).

3. Basal peripheral resistance was lower in diabetics than controls (36.0 mmHg. min/1, s.e.m. = 7.9, vs 42.3 mmHg.min/1, s.e.m. =2.8), but not significantly so.

4. Methoxamine markedly increased peripheral vascular resistance in both groups, but did not change coronary vascular resistance, due to autoregulation. The dose‐response curves of peripheral or coronary arteries to methoxamine showed no significant difference between diabetic and control sheep. Dose‐response curves for isoprenaline and noradrenaline infusion suggested there may be altered β‐receptor sensitivity in diabetes.

5. In conclusion, there are marked differences in the vascular beds of diabetic and normal sheep under basal conditions. In contrast to previous studies, α‐adrenoceptors are not different in diabetics, but further studies in unanaesthetized animals are indicated, as β‐receptor sensitivity may be altered in diabetes.