bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of hindlimb vascular resistance in rats chronically sympathectomized with 6‐hydroxydopamine
Authors: Clark D. W. J. , Phelan E. L.
Published: June 2007

1. Vascular resistance was measured after acute surgical denervation in the blood‐perfused hind limbs of adult normal rats and rats which had been treated with 6‐hydroxydopamine in the first 2 weeks of postnatal life. Vascular resistance was significantly higher in the limbs of 6‐hydroxydopamine treated rats.

2. No excess of vasoconstrictor materials was detected when blood from 6‐hydroxydopamine treated rats was used to perfuse the hind limbs of untreated rats or other 6‐hydroxydopamine treated rats.

3. Hind limb blood vessels of 6‐hydroxydopamine treated rats showed increased sensitivity to normal amounts of circulating vasoconstrictors of adrenal origin and to intra‐arterial infusions of noradrenaline and angiotensin.

4. Infusion of desipramine into the hindlimb blood vessels of 6‐hydroxydopamine treated rats did not increase vasoconstrictor responses to infused noradrenaline. Infusion of desipramine into the limbs of untreated rats increased responses to noradrenaline but these never attained the magnitude and duration of responses seen in limbs of 6‐hydroxydopamine treated rats.

5. The increased sensitivity to noradrenaline of hindlimb vessels from 6‐hydroxydopamine treated rats could partly be accounted for by an absence of neuronal uptake sites and partly by the development of non‐specific post‐junctional supersensitivity.
The role of the kidney in essential hypertension
Authors: Coleman Thomas G. , Guyton Arthur C. , Young David B. , DeClue James W. , Norman Roger A. , Manning R. Davis
Published: June 2007

1. Many forms of human and experimental hypertension begin with compromised renal function. Essential hypertension may be another such case.

2. The kidneys of subjects with essential hypertension excrete normal amounts of salt and water at higher‐than‐normal renal perfusing pressures. Other overt signs of renal dysfunction are few; renal disease is excluded by definition. However, renal blood flow and glomerular filtration rate are usually less than normal in essential hypertension.

3. Renal afferent resistance can be calculated from arterial pressure, renal blood flow, and an estimate of glomerular capillary pressure. These calculations indicate that afferent resistance is increased to two or more times normal in essential hypertension.

4. It is not clear whether afferent constriction causes hypertension or results from it. The ability of high pressure to produce vascular damage points to the latter. But, most essential hypertensives show low‐to‐normal plasma renin levels and a marked afferent dilation after saline loading. These observations do not suggest nephrosclerosis: they are consistent with a causal role for afferent constriction.

5. We can speculate that, in essential hypertension, there is a defect in one of the mechanisms that sets afferent resistance. Afferent constriction could result from extrinsic influences (neural or humoral) or something totally within the kidney, such as abnormal handling of information from the macula densa.

6. The effect of afferent constriction on salt‐and‐water excretion would theoretically be offset by elevated arterial pressure so that the actual salt‐and‐water excretion would be normal, but only so long as the arterial pressure remained elevated.
Independence of oral contraceptive‐induced changes in glucose tolerance and plasma cortisol levels
Authors: Cornish E. J. , Tesoriero W. M. , Briggs M. H. , Briggs M.
Published: June 2007

1. Following a 50 g oral glucose load, plasma glucose concentrations and plasma cortisol concentrations were measured in twenty‐five young healthy women.

2. When compared to controls, oral contraceptive users (OC‐users) were found to show a small but significant decrease in glucose tolerance while plasma cortisol values were increased more than two‐fold.

3. The decreased glucose tolerance in OC‐users did not show a significant correlation with raised plasma cortisol levels.
UNUSUAL EFFECT OF SOME α‐MERCAPTOACRYLIC ACIDS ON METABOLISM OF ZINC IN THE RAT
Authors: Prakash N. J. , Schechter Paul J. , Giroux Eugene , Sjoerdsma Albert
Published: June 2007

1. Gavage of rats with β‐aryl derivatives of α‐mercaptoacrylic acid resulted in pronounced and sustained elevation of serum zinc concentration. Greater than ten‐fold increases above normal zinc levels were attained 2–8 h after doses of 50 mg/kg of the phenyl and furan derivatives.

2. These compounds were rapidly absorbed from the rat gastrointestinal tract and could be detected in serum for several days after a single dose. The return of serum zinc concentration to the normal level paralleled clearance of the mercaptoacrylic acid from plasma.

3. Close to 100% of the zinc and of the α‐mercapto‐β‐(2‐furan)acrylic acid (MFA) in serum 4 h after administration of the compound were bound to serum macromolecules.

4. MFA decreased excretion of endogenous zinc; it altered neither the gastrointestinal absorption of zinc nor serum concentrations of copper, albumin and total protein.

5. These compounds appear to mobilize zinc from tissue stores and retard zinc clearance from plasma.
FORMATION OF A TERNARY COMPLEX WITH SERUM ALBUMIN: AN EXPLANATION FOR THE EFFECT OF α‐MERCAPTO‐β‐(2‐FURAN) ACRYLIC ACID ON RAT PLASMA ZINC CLEARANCE
Authors: Giroux Eugene , Prakash N. J. , Schechter Paul J.
Published: June 2007

1. Four, six and eight hours after gavage of rats with α‐mercapto‐β‐(2‐furan) acrylic acid (MFA) (25 mg/kg) serum zinc concentration was increased ten‐fold over control levels and a mean molar ratio of 1 albumin:0.4 zinc:0.8 MFA was found for seventeen sera.

2. At pH 7.5 a maximum of 1 mole of MFA could be bound per mole of metal‐free bovine serum albumin.

3. In the presence of zinc ion, albumin‐zinc‐MFA complexes formed, since for each mole of albumin‐zinc complex an additional mole of MFA could be bound to albumin. Complexes up to a molar stoichiometry of 1 albumin:2 zinc:3 MFA were prepared.

4. MFA stabilized the albumin‐zinc complex against dissociation.

5. Formation of similar complexes in vivo may account for the markedly delayed clearance of plasma zinc seen in rats administered β‐aryl derivatives of α‐mercaptoacrylic acid.
THE PARTICIPATION OF ENTERIC INHIBITORY NERVES IN ACCOMMODATION OF THE INTESTINE TO DISTENSION
Authors: Furness J. B. , Costa M.
Published: June 2007

1. The amounts by which various weights distended isolated segments from the distal colons of guinea‐pigs were measured.

2. Tetrodotoxin substantially reduced the distensibility of the intestine, but bretylium, guanethidine, hyoscine and methysergide had no significant effect.

3. It is concluded that a local reflex involving enteric inhibitory nerves causes an accommodation of the intestine to stretch.
BLOCKADE BY PHENTOLAMINE OF THE POTENTIATION OF HISTAMINE‐INDUCED VASOCONSTRICTION CAUSED BY SEROTONIN AND METHYSERGIDE IN THE RABBIT EAR ARTERY
Authors: Carroll P. R. , Morgans D. , Glover W. E.
Published: June 2007

1. In subconstrictor doses, both serotonin and methysergide potentiated the vasoconstrictor responses to histamine in the isolated artery of the rabbit ear.

2. In the presence of phentolamine (5 μg/ml) the potentiating actions of serotonin and methysergide were significantly reduced.

3. This blocking action of phentolamine could be overcome by increasing the concentration of serotonin or by washing the preparation.

4. In arteries taken from rabbits pretreated with reserpine, serotonin still potentiated the response to histamine and phentolamine still blocked this potentiation.

5. The concentration of phentolamine required to block potentiation also blocked the direct constrictor response to serotonin. It did, however, produce a significantly greater blockade of the vasoconstrictor response to noradrenaline.

6. The results indicate that the action of phentolamine in blocking the vascular potentiation produced by serotonin and methysergide is not due to a blockade of α‐receptors.
SYMPATHETIC CARDIOVASCULAR REFLEX INITIATED BY BRADYKININ‐INDUCED STIMULATION OF CARDIAC PAIN RECEPTORS IN THE DOG
Authors: Staszewska‐Barczak Janina , Dusting G. J.
Published: June 2007

1. Bradykinin (0.02–5 μg) applied to the epicardium of the left ventricle in the open‐chest, anaesthetized dog, elicits dose‐related reflex pressor effects and acceleration of the heart rate.

2. Bradykinin‐induced reflex tachycardia was suppressed after the blockade of β‐adrenoceptors with propranolol, whereas reflex pressor responses were prevented by blocking the α‐adrenoceptor sites with phenoxybenzamine.

3. Vagotomy and atropine treatment did not affect reflex hypertension and tachycardia to epicardial bradykinin.

4. After spinal section at C1, the pressor responses to epicardial bradykinin were significantly reduced, but still present in all but one experiment. A small acceleration of the heart occurred in two out of five spinal dogs with intact vagi and was absent in three vagotomized spinal dogs.

5. The results indicate the reflex activation of the sympathetic outflow to the heart and blood vessels, mediated mainly at a supraspinal level as a predominant mechanism for the cardiovascular response initiated by bradykinin‐induced stimulation of cardiac pain receptors.
THE INFLUENCE OF ALTERATIONS IN THE CARDIAC LOADING CONDITIONS ON INDICES OF MYOCARDIAL CONTRACTILITY IN THE ANAESTHETIZED DOG
Authors: Angus J. A. , Richmond D. R. , Cobbin L. B. , Goodman A. H.
Published: June 2007

1. An online analogue computer was used to measure myocardial contractility as the ratio dP/dt/IIT where dP/dt is maximum rate of change of left ventricular pressure and IIT is integrated isometric tension.

2. In the open thorax anaesthetized dog, max (dP/dt) and dP/dt/IIT were compared during alterations in preload, by partial vena caval occlusion, and changes in after‐load obtained by acetylcholine injections and by partial occlusion of the descending thoracic aorta.

3. A fall in preload lowered max (dP/dt) but did not alter dP/dt/IIT A rise and fall in afterload produced respectively an increase and decrease in max (dP/dt) but dp/dt/IIT was unaltered.

4. From expanded time base recordings, the time from the start of aortic flow (EM flowmeter) to max (dP/dt) was measured to indicate the relationship between valve opening and rnax (dP/dt). At low preload or elevated afterload the aortic valve opened well after max (dP/dt) had been reached. When the afterload fell, max (dP/dt) occurred after the opening of the aortic valve.

5. Positive inotropic stimulation following intravenous isoprenaline caused a marked elevation in dP/dt/IIT. However, the rise in max (dP/dt) was attenuated in comparison to dP/dt/IIT by a marked fall in afterload and thus early opening of the aortic valve.

6. It is concluded that max (dP/dt) is very sensitive to alterations in preload or afterload but the index——‐dP/dt/IIT is normalized so that changes in end diastolic fibre length do not alter this index. When the afterload falls max (dP/dt) is no longer determined in the isovolumic phase of contraction so that magnitude of rnax (dP/dt) is reduced. However, it is an empirical finding that IIT also falls so that the ratio is unaltered. dP/dt/IIT is a useful index of myocardial contractility that is insensitive to changes in preload or afterload.
THE EFFECT OF APOMORPHINE AND CLONIDINE ON LOCOMOTOR ACTIVITY IN MICE AFTER LONG TERM TREATMENT WITH HALOPERIDOL
Authors: Dunstan Robin , Jackson D. M.
Published: June 2007

1. Mice were given haloperidol (approximately 3 mg.kg−1 day−1) or vehicle for 21 days and then withdrawn from the drug. All tests were performed 4 days after withdrawal.

2. Haloperidol treated mice (premedicated with reserpine plus a‐methyl‐p‐tyrosine) displayed an increased locomotor response to apomorphine and to apomorphine plus clonidine, but neither haloperidol‐ or vehicle‐treated animals revealed any stimulant response to clonidine.

3. In mice which had not been pretreated with reserpine plus a‐methyl‐p‐tyrosine, clonidine produced a significant stimulation of locomotor activity in animals withdrawn from haloperidol but not in those withdrawn from the vehicle. Phen‐oxybenzamine blocked the locomotor stimulant difference between these two groups, but did not completely antagonize the stimulant effect of clonidine in mice withdrawn from haloperidol. Pimozide was largely effective in blocking the clonidine‐induced stimulation. Co‐administration of phenoxybenzamine and pimozide was completely effective in blocking the stimulant effect of clonidine in mice withdrawn from haloperidol.

4. The evidence for a change in catecholamine receptor sensitivity was supported by the increased stimulant effect of dexamphetamine in the haloperidol‐treated, compared to the vehicle‐treated animals.

5. The data suggest that there is a change in the functional responsiveness of both adrenergic and dopaminergic receptors after withdrawal from long term haloperidol treatment.
A COMPARISON OF THE CARDIAC ACTIONS OF DOPAMINE AND NORADRENALINE IN ANAESTHETIZED DOGS AND GUINEA‐PIG ATRIA
Authors: Einstein Rosemarie , Barrett A. M.
Published: June 2007

1. The positive chronotropic and inotropic actions of dopamine and noradrena‐line have been compared in anaesthetized dogs and isolated guinea‐pig atria.

2. Inotropic activity was measured with a strain‐gauge arch in vagotomized dogs or estimated from max (dp/dt) in dogs with denervated hearts.

3. The effects of propranolol and haloperidol on the concentration‐response curves to both amines were studied in isolated atria.

4. In anaesthetized vagotomized dogs noradrenaline was more potent than dopamine but dopamine appeared to have a selective inotropic action, less apparent with noradrenaline. In denervated hearts, doses of noradrenaline and dopamine which caused similar increases in max (dp/dt) also caused similar increases in heart rate.

5. In isolated atrial preparations, concentrations of dopamine and noradrenaline which produced similar increases in force of contraction also had similar chronotropic effects.

6. Propranolol produced a shift to the right of the concentration‐response curves to both dopamine and noradrenaline but the antagonism of noradrenaline was quantitatively greater. Haloperidol had no effect in concentrations below those found to cause general tissue depression.

7. It is concluded that neither dopamine nor noradrenaline show any real difference in their relative inotropic and chronotropic activities in the absence of autonomic innervation.
THE INTERACTION OF FRUCTOSE, DEXTROSE AND ETHANOL ON HUMAN PERFORMANCE
Authors: Franks H. M. , Hagedorn H. , Hensley V. R. , Hensley W. J. , Starmer G. A.
Published: June 2007

1. The effects of orally administered fructose (1.2 g.kg−1) and dextrose (1.2 g.kg−1) on the performance decrement induced by ethanol (1.0 g.kg−1) in a series of perceptual, cognitive and motor tests were studied in twelve healthy, paid University student volunteers using a double‐blind cross‐over design. Ethanol was consumed at a constant rate over 20 min and the hexoses or placebo were given approximately 40 min later.

2. The peak blood ethanol concentration was attained earlier when the subjects also received either hexose than after placebo but although its rate of fall was unaffected, significantly lower ethanol concentrations were encountered in the hexose‐treated groups in the latter part of the experiment.

3. In general, the subjects were impaired to a slightly lesser degree when they received a combination of hexose and ethanol than after ethanol alone. There were no differences between the effects of fructose and dextrose.

4. The results do not support contentions that fructose is able to accelerate a return to sobriety and observed differences between hexose and placebo‐treated groups were attributed to an effect on the absorption of ethanol rather than its metabolism.
THE EFFECTS OF SOME BRONCHODILATOR AND ANTI‐INFLAMMATORY DRUGS ON PROSTAGLANDIN F2a‐INDUCED CONTRACTION OF GUINEA‐PIG ISOLATED TRACHEA
Authors: McIntyre Heather J. , Temple Diana M.
Published: June 2007

1. The bronchodilator drugs isoprenaline, salbutamol, theophylline and prostaglandin E1 (PGE1) relaxed the guinea‐pig isolated tracheal chain preparation dose‐dependently and their potencies were compared by EC50 values.

2. The non‐steroid anti‐inflammatory drugs flufenamate, mefenamate and phenylbutazone also relaxed the preparation dose‐dependently, but were less potent than the sympathomimetic drugs and PGE1.

3. The contractile response to a submaximal concentration of prostaglandin F2a (PGF2a) was antagonized by flufenamate, mefenamate, phenylbutazone, aspirin, theophylline, isoprenaline, salbutamol and PGE1, at concentrations similar to or less than the clinical peak plasma levels in man. A relatively higher concentration of indomethacin was required.

4. The antagonism was relatively specific for PGF2a in the case of the fenamates, which did not cause comparable reductions in responses to equi‐effective concentrations of histamine and carbachol. The other anti‐inflammatory drugs, theophylline and the sympathomimetic drugs were less or non‐specific.

5. The nature of the shifts in the log dose‐response curve for PGF2a caused by increasing concentration levels of flufenamate indicates a dual competitive/non‐competitive type of antagonism.
COUNTERCURRENT EXCHANGE OF EIIGHLY DIFFUSIBLE TRACERS IN SKELETAL MUSCLE: ITS ABSENCE IN THE LUNG
Authors: Smiley M. , Lawson M. , Garlick D.
Published: June 2007

1. Multi‐exponential rates of desaturation of highly diffusible tracers were observed in vascular washout of skeletal muscle. This led to the hypothesis of counter‐current exchange of such solutes between pre‐ and postcapillary vessels which are closely apposed in skeletal muscle. By contrast, in the lung pre‐ and postcapillary vessels are separated by alveolar tissue.

2. The ‘indicator diffusion’ method was used in studies on both organs. A vascular reference tracer and a highly diffusible tracer (125I‐iodoantipyrine, 3HOH, 14CO2) were rapidly injected intra‐arterially. Venous samples were collected to determine tracer concentrations. From the venous concentrations of the reference and diffusible tracers extraction of the diffusible tracer into the tissue could be determined.

3. In the lung the diffusible tracers conformed to theoretical predictions. High extractions of diffusible tracers into lung tissue occurred in early venous samples. The values declined in subsequent samples as a result of significant tissue concentrations of the diffusible tracers.

4. At low flows in skeletal muscle precession frequently occurred of the diffusible tracer ahead of the reference tracer. Extractions of diffusible tracers were low in early samples and subsequently increased to a maximum. At high flows these effects were considerably less. These features are characteristic of countercurrent exchange.

5. In vivo in resting muscle, pre‐ to postcapillary shunting of O2 and of CO2 in the reverse direction would become cyclical. The hypoxaemia and hypercarbia would dilate precapillary vessels leading to increased flow thus reducing diffusional shunting of the respiratory gases. The resultant rise in oxygen tension would allow vascular constriction reducing flow and increasing shunting. This is consistent with vasomotion. In exercising muscle the marked increase in flow would minimize this shunting.
CHRONOPHARMACOLOGY OF STRYCHNINE AND ALLYLGLYCINE IN THE MOUSE
Authors: Piepho R. W. , Friedman A. H.
Published: June 2007

1. The response of individually caged mice to the lethal actions of allylglycine and strychnine was evaluated in animals previously conditioned on an LD 12:12 (12 h light‐12 h darkness) schedule in a controlled environment.

2. These convulsant agents were most toxic at 18.00 hours (during the light phase), and least toxic in the dark phase of the programmed lighting schedule. The relationship is considered of the circadian fluctuations in levels of inhibitory transmitter substances to the time‐linked action of convulsant agents.
EQUINE ANGIOTENSIN CONVERTING ENZYME: A ZINC METALLOENZYME
Authors: Fernley Ross T.
Published: June 2007

1. Angiotensin I converting enzyme from horse plasma has been extensively purified and shown to be homogeneous by disc‐gel electrophoresis.

2. The metal ion involved in the catalytic reaction of the enzyme has been identified for the first time as zinc by atomic absorption spectrometry.

3. A number of other physicochemical properties of the enzyme are described and compared with results obtained by other investigators. The molecular weight was determined by gel filtration to be 113 000 daltons. The pH maximum was found to be 7.4. The chloride activation of the enzyme appears to act by facilitation of substrate binding to the enzyme.

4. By use of enzyme inhibitors, tyrosine has been implicated as a functional residue at the active site of the enzyme.

5. The enzyme shows a fairly high degree of specificity towards its substrates.
SPECIES DIFFERENCE IN THE β1/β2‐ADRENOCEPTOR SELECTIVITY OF SM220CL IN THE CAT AND GUINEA‐PIG
Authors: Bohmer K. , Raper C.
Published: June 2007

1. The β‐receptor stimulant effects of Sm220Cl, dl‐N‐ (1,1‐dimethyl‐3‐phenylpropyl)‐2‐hydroxy‐2(3,4‐dihydroxy‐2‐methoxyphenyl)ethylamine, and (‐)‐isoprenaline have been compared in isolated atrial (β1) and tracheal (β2) preparations from guinea‐pigs and cats.

2. The compounds were also tested for their ability to increase the heart rate (β1), reduce serotonin‐induced increases in pulmonary resistance (β2), and decrease soleus muscle contractility (β2) in vivo in the two species.

3. In all experiments cumulative concentration or dose‐effect curves were established, EC50 or ED50 values obtained and molar activity‐ratios (Sm220Cl: (‐)‐isoprenaline) calculated.

4. Calculated selectivity ratios [activity‐ratio (heart):activity‐ratio (bronchial smooth muscle)] from the in vitro experiments showed that Sm220Cl possessed β2‐receptor selectivity. This was more marked in guinea‐pig than in cat preparations.

5. In the anaesthetized animals this species difference was more apparent; in cats Sm220Cl was non‐selective in its actions for β1‐ and β2‐receptor mediated responses, while marked β2‐receptor selectivity was obtained in the guinea‐pig.

6. Since in both species the activity‐ratios for β2‐receptor mediated actions are similar, the differences in the β1/β2‐receptor selectivity of Sm220Cl are caused by the divergent cardiac effects produced by the drug.
CARDIAC ARREST TEMPERATURE: THE EFFECT OF ETHYL ALCOHOL AND CARBON DIOXIDE ON RATS, GUINEA‐PIGS AND ISOLATED RAT HEARTS
Authors: Duthie Ashley M. , White J. Forster
Published: June 2007

1. Previous clinical and experimental reports have suggested that the systemic administration of ethyl alcohol permits lower body temperatures before the onset of hypothermic cardiac arrest.

2. In the investigations described here, the effect of ethyl alcohol on the temperature at which cardiac arrest occurred in rats, guinea‐pigs and isolated rat hearts was studied. Comparison was also made of the difference between pulmonary ventilation with air and with 5% carbon dioxide in oxygen.

3. The results demonstrated that both the administration of ethyl alcohol and ventilation with 5% carbogen reduced the cardiac arrest temperature of rats. Ethyl alcohol did not influence the cardiac arrest temperature of guinea‐pigs nor of isolated rat hearts.
THE EFFECTS OF SEROTONIN PRECURSORS ON THE PRESSOR RESPONSE TO INTRAVENOUS CLONIDINE IN CONSCIOUS RATS
Authors: Nolan P. L.
Published: June 2007

1. The interaction of the biosynthetic precursors of serotonin with the a‐adrenoceptor‐mediated pressor response to intravenous clonidine was investigated in unanaesthetized rats.

2. Pretreatment with 100 mg/kg of either L‐tryptophan or 5‐hydroxytryptophan (5‐HTP) reduced the magnitude of the pressor response elicited by intravenous clonidine (25 μg/kg) to 15% and 11%, respectively, of that observed in control rats.

3. The depression by L‐tryptophan of the clonidine‐induced pressor response could be prevented by pretreatment with either the L‐aromatic amino acid de‐carboxylase inhibitor Rö‐4– 4602 or the serotonin antagonist methysergide.
CHOLIC ACID AND THE HEART: IN VITRO STUDIES OF THE EFFECT ON HEART RATE AND MYOCARDIAL CONTRACTILITY IN THE RAT
Authors: Joubert P.
Published: June 2007

1. Cholic acid has a dose‐dependent negative chronotropic effect on isolated atria ofWistar rats.

2. The positive inotropic effect of cholic acid is the result of a negative chronotropic effect and can be eliminated by electrical pacing.

3. Cholic acid does not appear to exert its negative chronotropic effect through cholinoceptors and alterations in bath concentrations of calcium and potassium does not influence this effect significantly.

4. Cholic acid is a functional antagonist of isoprenaline.

5. It is suggested that cholic acid exerts its negative chronotropic effect by forming a monolayer on the surface of the cell membrane, thereby mechanically interfering with membrane function.
CARDIAC AND BRONCHIAL β‐ADRENOCEPTOR ANTAGONISTIC POTENCIES OF ATENOLOL, METOPROLOL, ACEBUTOLOL, PRACTOLOL, PROPRANOLOL AND PINDOLOL IN THE ANAESTHETIZED DOG
Authors: Harms Herman H. , Spoelstra Albert J. G.
Published: June 2007

1. The β‐adrenoceptor antagonists atenolol, metoprolol, acebutolol, practolol, propranolol and pindolol have been tested for their ability to reduce isoprenaline‐induced bronchodilation and tachycardia in the anaesthetized dog.

2. Atenolol, metoprolol, acebutolol and practolol all possessed a similar degree of cardioselectivity in this animal model.
INTRARENAL MECHANISM FOR RENAL VASOCONSTRICTION RESULTING FROM STIMULATION OF THE URETER IN THE DOG
Authors: Robie N. W. , McNay J. L.
Published: June 2007

1. The mechanism responsible for ipsilateral renal vasoconstriction resulting from mechanical stimulation of the ureter was examined using the pharmacological antagonists saralasin, SQ20881, indomethacin, atropine and phentolamine.

2. A segment of PE tubing was implanted in the left ureter, patency being well maintained. Three to four days later renal blood flow was measured bilaterally and antagonists administered intravenously.

3. The mechanism responsible for vasoconstriction could not be attributed to either increased intrarenal noradrenaline or angiotensin, nor to a decreased activity of prostaglandins, kinins or acetylcholine.

4. Histological and bacteriological examination also proved negative.

5. Thus, additional evidence of an unidentified intrarenal mechanism causing vasoconstriction is presented.
PRESSOR ACTION OF PYRIDEVE‐2‐ALDOXIME IN MALATHION POISONING*
Authors: Chang P. , Ganendran A.
Published: June 2007

1. Intravenous injections of pyridine‐2‐aldoxime (PAM) produced a marked, prolonged and dose‐related rise in blood pressure in anaesthetized cats treated with malathion (MT) and without malathion (NMT).

2. The pressor effect of PAM was significantly reduced by phentolamine and phenoxygenzamine, but unaffected by hexamethonium.

3. Pretreatment with guanethidine and reserpine almost completely abolished the pressor response to PAM.

4. The results indicate that PAM has a potent sympathomimetic action which appears to be mediated through release of catecholamines from storage sites.
L‐TRYITOPHAN‐INDUCED DEPRESSION OF THE PRESSOR RESPONSE TO CLONIDINE IN ANAESTHETIZED RATS
Authors: Nolan P. L. , Brazenor R. M.
Published: June 2007

1. The interaction of the serotonin precursor L‐tryptophan with the pressor responses of the anaesthetized rat to the intravenous injection of clonidine, adrenaline and angiotensin has been studied.

2. Pretreatment of rats with L‐tryptophan (100 mg/kg) depressed the pressor response to clonidine but had no effect on the responses elicited by adrenaline or angiotensin.

3. The L‐tryptophan‐induced depression of the clonidine response was prevented by pretreating rats with either Rö 44602, carbidopa, BW 172C58, methys‐ergide or by pithing.

4. Intravenous infusions of serotonin depressed the pressor responses to clonidine, adrenaline and angiotensin in both intact anaesthetized and pithed rats.

5. It is concluded that the depressant action of L‐tryptophan is dependent on its conversion within the periphery to serotonin. This action is also dependent on or mediated by the sympathetic nervous system.
MEASUREMENT OF 42K CONCENTRATION IN THE MUCOSAL PORTION OF THE INTESTINE WITHOUT TISSUE SAMPLES: AN APPROACH TO THE MEASUREMENT OF MUCOSAL BLOOD FLOW IN THE DOG
Authors: Eade M. N. , Arroll B. , Quinn J. P.
Published: June 2007

1. The concentration of 42K within the jejunal mucosa was measured by intraluminal miniature Geiger‐Müller tubes shielded with platinum foil.

2. Isotope concentration measured by tissue assay of jejunal mucosa gave similar results to that obtained by the Geiger‐Müller tubes.

3. Isotope measurement by shielded Geiger‐Müller tubes obviates the need for tissue samples and permits repeat measurement in the same animal. This should find physiological application in measuring the mucosal portion of total intestinal blood flow by the indicator fractionation technique.
EFFECT OF CIMETIDEME ON THE HEALING OF RESTRAINT‐INDUCED GASTRIC EROSIONS IN THE RAT
Authors: Lee S. P. , Clarke A. C. , Tasman‐Jones C.
Published: June 2007

1. Rats after a 24 h restraint developed acute gastric erosions. Cimetidine in a dose of 100 mg/kg body weight was given subcutaneously every 8 h to a group of 150 rats after restraint. A second group received saline subcutaneously (placebo group).

2. Erosions in the placebo group required up to 45 days to heal (median healing time approximately 24 days). Cimetidine treatment reduced the median healing time to approximately 12 days.

3. Cimetidine in this dose promotes healing of acute gastric erosions in the rat induced by restraint.
A SEQUENTIAL STUDY OF ADRENOCORTICOSTEROID LEVEL IN HUMAN PREGNANCY
Authors: Wintour E. M. , Coghlan J. P. , Oddie C. J. , Scoggins B. A. , Walteis W. A. W.
Published: June 2007

1. Peripheral plasma levels of aldosterone, corticosterone, Cortisol, 11‐deoxycorticosterone (DOC) and 11‐deoxycortisol were measured sequentially throughout pregnancy in eleven women.

2. Mean plasma concentrations were significantly increased above non‐pregnant values at 8 weeks for DOC, at 12 weeks for corticosterone, Cortisol and 11‐deoxycortisol, but not until 24 weeks for aldosterone.

3. It is suggested that during human pregnancy, the maternal adrenal is responding differently to corticotrophin, pituitary or placental, and that other factors, for example prolactin, may be stimulating the adrenal directly or modifying the action of corticotrophin.
SELECTIVE STIMULATION OF INTRACARDIAC PREGANGLIONIC VAGAL FIBRES OF THE DOG ATRIUM
Authors: Chiba S.
Published: June 2007

1. Direct electrical stimulation (0.05 ms, 5.0 V and 30 Hz) caused negative chronotropic and inotropic effects on the blood‐perfused, isolated dog atrium.

2. These negative effects of electrical stimulation were significantly blocked not only by treatment with atropine or tetrodotoxin, but also by hexamethonium, although hexamethonium did not modify the effects of injected acetylcholine.

3. These results suggest that direct electrical stimulation on the isolated, blood‐perfused dog atrium readily causes a release of acetylcholine by excitation of parasympathetic pre‐ganglionic fibres.
EFFECTS OF VARIOUS DRUGS ON THE OSMOTIC LYSIS OF RAT MAST CELLS
Authors: Day R. O. , Wade D. N.
Published: June 2007

1. Rat mast cells were exposed to low osmotic pressures to produce a ‘nonspecific’ disruption of the mast cell, with release of histamine along with other intracellular contents.

2. The effect of non‐steroidal anti‐inflammatory drugs and various other drugs upon osmotically induced histamine release was examined.

3. Representative non‐steroidal anti‐inflammatory drugs indomethacin, phenylbutazone and flufenamic acid, the acidic compounds ethacrynic acid, iopanoic acid and probenecid, and the local anaesthetic lignocaine, all caused a dose‐dependent facilitation of osmotically induced histamine release compared to controls. All drugs were active at 0.1 mmol/1.

4. The previously observed inhibition of compound 48/80 and the antigen‐induced histamine release from rat mast cells by similar concentrations of the drugs used in the present study are unlikely to be due to mast cell plasma membrane stabilization.
THE NATURE OF THE PRESSOR RESPONSE TO CAROTID ARTERY OCCLUSION IN THE HEXAMETHONIUM‐TREATED RAT
Authors: Chahl Loris A. , Cross R. B.
Published: June 2007

1. The blood pressure monitored from the cannulated right carotid artery and heart rate responses to occlusion of the intact left carotid artery were investigated in rats.

2. Hexamethonium abolished the response to ganglion stimulants but not that to carotid occlusion, although the time course and nature of the response were altered.

3. The pressor response to carotid occlusion in the presence of hexamethonium was not abolished by carotid sinus denervation, vagal section, tubocurarine, atropine, ethyl alcohol or an angiotensin II antagonist, but it was abolished by high doses of phenoxybenzamine. In six out of eight experiments the response was not abolished by cervical cord section.

4. It was concluded that the pressor response to carotid occlusion in the presence of hexamethonium in the rat involves an adrenergic mechanism which is at least in part independent of the autonomic ganglia, and which is mediated by an agent liberated from the brain, possibly under conditions of cerebral ischaemia.
INTRARENAL ACTION OF ANGIOTENSIN II IN RESTORING RENAL ARTERY PRESSURE AFTER ACUTE RENAL ARTERY STENOSIS
Authors: Anderson W. P. , Korner P. I. , Johnston C. I. , Angus J. A. , Casley D. J.
Published: June 2007

1. The renal artery of conscious dogs was acutely narrowed over 30 s to reduce renal artery pressure distal to the stenosis to 40 mmHg and the stenosis was maintained for 1 h. The distal renal artery pressure was rapidly restored to a plateau slightly below pre‐stenosis values within 10–15 min. Rises in systemic blood pressure and plasma renin activity were small and transient.

2. This restoration was an active process, mediated by the intrarenal effects of angiotensin II (AH), since it was greatly diminished or abolished when the renal artery was narrowed in the presence of angiotensin I‐converting enzyme inhibitor or angiotensin receptor antagonist (l‐Sar‐8‐Ue All). However, it was not diminished by ‘total’ autonomic effector blockade.

3. This angiotensin II‐mediated restoration of renal artery pressure may be of homeostatic significance for the maintenance of glomerular filtration rate.
DECREASED CARDIAC β‐ADRENOCEPTORS IN HYPERTENSIVE RATS
Authors: Woodcock E. A. , Funder J. W. , Johnston C. I.
Published: June 2007

1. β‐Adrenoceptors have been investigated in cardiac and renal cell membranes from hypertensive and normal rats.

2. The 125I‐labelled β‐adrenoceptor antagonist l‐(4‐iodophenoxy)‐3‐isopropyl‐aminopropan‐2‐ol was used to measure directly the number and affinity of receptors.

3. Cardiac membranes from hypertensive rats had a lower concentration of β‐adrenoceptors than membranes from control normotensive animals, but the affinities of the receptors remained unchanged. Receptor concentration decreased by half and was similar in each of the three models of experimental hypertension investigated.

4. In contrast, kidney membranes from hypertensive animals had the same β‐adrenoceptor concentration and affinity as membranes from normotensive rats.

5. The decrease in cardiac β‐adrenoceptor concentration may reflect an increase in cardiac sympathetic drive in these experimental hypertensive models.
THE MEASUREMENT OF GLOMERULAR BLOOD FLOW IN THE RAT KIDNEY: INFLUENCE OF MICROSPHERE SIZE
Authors: Sabto J. , Bankir L. , Grünfeld J. P.
Published: June 2007

1. Radioactively labelled microspheres were used to determine glomerular blood flow in glomerular populations with distinct vascular characteristics. Two batches of microspheres (15 ± 5.0 μm diameter and 7.0–10 μm diameter) were utilized.

2. The results show that the larger microspheres overestimate the superficial glomerular blood flow (414 ± 61 nl/min, mean ± s.e.m.) and underestimate the deep glomerular blood flow (98 ± 10 nl/min), when compared with the data obtained with 7.0–10 μm diameter microspheres (317 ± 30 nl/min and 209 ± 23 nl/min, respectively).

3. The rheological artefact associated with the use of larger microspheres is confirmed by finding an uneven size distribution of microspheres lodged in the glomeruli. In each of three experiments, the mean diameter of 200 microspheres lodged in the superficial glomeruli (16.43 ± 0.27 μm, 15.87 ± 0.23/mi and 16.58 ± 0.27 Jim) was significantly greater than that found in the deep glomeruli (15.36 ± 0.15μm, 15.25 ± 0.21 μm and 15.73 ± 0.24μm; P<0.01, <0.05 and < 0.01, respectively). No such difference was detected when the 7.0–10 μm spheres were used.

4. Glomerular blood flow can be measured at all depths of the rat's cortex and the demonstrated rheological artefact associated with use of the larger spheres is circumvented with the use of 7.0–10 μm microspheres.
HAEMODYNAMIC EFFECTS OF ISOMETRIC HANDGRIP EXERCISE IN PATIENTS CONVALESCENT FROM MYOCARDIAL INFARCTION
Authors: Baccelli G. , Valentini R. , Gregorini L. , Cellina G. , Mancia G. , Ludbrook J. , Zanchetti A.
Published: June 2007

1. Cardiac performance in response to 30% maximal isometric handgrip exercise was studied in fourteen patients convalescing uneventfully from a first myocardial infarction. In each patient, heart rate, mean arterial blood pressure and cardiac index were measured, and total peripheral resistance was calculated. The covariance of changes in the mean arterial blood pressure and cardiac index in these patients was matched against tolerance limits calculated from published data for normal subjects.

2. All patients had normal haemodynamic values at rest, and showed the usual rise of heart rate and mean arterial pressure during handgrip exercise. However, in six patients (group 1) the rise in mean arterial pressure was, as in normal subjects, accounted for mainly by a rise in cardiac index, with no consistent change in peripheral resistance. In eight patients (group 2), the mean arterial pressure rose to the same level as in group 1, but with a consistent increase in peripheral resistance and a smaller rise in the cardiac index.

3. It is suggested that in a substantial proportion of patients who are making a seemingly uncomplicated recovery from myocardial infarction, it may be possible to unmask an impairment of left ventricular function by means of isometric handgrip exercise.
CARDIAC EFFECTS OF SALBUTAMOL‐INDUCED HYPOKALAEMIA IN THE CONSCIOUS DOG
Authors: Wahlqvist M. L. , Shanahan E. A. , Dennis P. M. , Pullan P. T. , Wilmshurst E. G.
Published: June 2007

1. Infusion of salbutamol (3.0 μg/min after a bolus injection of 100 μg) produced hypokalemia in conscious dogs.

2. Measurement of arterial and coronary sinus potassium differences revealed no significant potassium loss from the heart with established hypokalaemia.

3. Shortly after the initial salbutamol bolus and before steady‐state hypokalaemia had been achieved during salbutamol infusion, a prolongation of QTC occurred; this corresponded to a significant myocardial potassium loss of ‐0.12 mmol/1 plasma.

4. Urinary electrolyte excretions indicated that the hypokalaemia was not due to urinary potassium loss.

5. It was deduced that potassium had moved intracellularly. No change in hydrogen ion status occurred to account for this. Pronounced rises in plasma insulin immunoreactivities during salbutamol infusions suggested this as one mechanism for potassium shifts.
A NOVEL ACTIVITY CAGE FOR RATS: CHARACTERIZATION OF SOME PHENYLETHYLAMINE DERIVATIVES WITH CENTRAL STIMULANT AND DEPRESSANT EFFECTS
Authors: Dunn R. I. , Ghosh P. , Bolt A. G. , Mrongovius R. I.
Published: June 2007

1. A novel activity cage for rats is described. Eight light beams are aimed at a light‐conducting perspex rod at the centre of a cylindrical cage. The photoresistor at the end of the rod detects the changes in light intensity produced by interruption of the light beams.

2. The apparatus is simple to operate and was capable of detecting small differences in the motor activity of groups of rats.

3. Dose‐dependent increases in motor activity were produced by dexampheta‐mine (1.36 to 27.3 μmol/kg, i.p.). The depressant effects produced by 20 μmol/kg doses of norfenfluramine were greater than those of fenfluramine. Large doses (100 μmol/kg) of tranylcypromine stimulated motor activity whereas its m‐isomer, m‐2‐phenylcyclopropylamine, depressed motor activity.
THE EFFECTS OF THYROID STATUS ON DIGOXIN DISTRIBUTION IN THE RAT
Authors: Veroni M. , Shenfield G. M.
Published: June 2007

1. Tritiated digoxin was injected intravenously into euthyroid, hyperthyroid and hypothyroid rats. The rats were killed at intervals up to 24 h and tritium in serum and tissues counted.

2. Serum concentrations of tritium in the hyperthyroid animals were less than in the control group, whereas the concentrations in the hypothyroid group were similar to those in the control group.

3. Cardiac tissue concentrations of tritium were higher in the hyperthyroid group than in the control group, but in the hypothyroid group were similar to the control group.

4. The decreased serum levels in the hyperthyroid rats were probably due to an increased volume of distribution.

5. Pharmacological resistance to digoxin in hyperthyroidism must be due to some alteration in cardiac function and it is suggested that this is an increase in Na/K ATPase receptors.
DIFFERENT POTENCIES OF [ASP1, ILE5]‐ AND [ASN1 VAL5]‐ANGIOTENSIN II IN STIMULATING ALDOSTERONE PRODUCTION FROM RAT ADRENAL ZONA GLOMERULOSA CELLS IN VITRO
Authors: Mendelsohn F. A. O.
Published: June 2007

1. Rat adrenal zona glomerulosa cells were incubated in Krebs Ringer bicarbonate medium containing bovine serum albumin. Aldosterone production was measured by radioimmunoassay.

2. Both [Asp1, Ile5]‐angiotensin II ('free acid') and (Asn1, Val5]‐angiotensin II ('amide'), (10−5 mol/1), stimulated aldosterone output but the free acid compound produced a larger increase in steroid output than the amide.

3. This difference in steroidogenic activity could not be explained by differences in purity or initial concentration or by stimulation of the contaminating fasciculata cells.

4. However, serial bioassays of the media revealed that the amide form of angiotensin was degraded more rapidly than the free acid form.

5. The different potency of these two forms of angiotensin II could explain some of the reported discrepancies of the action of angiotensin II on rat adrenal tissue or cells in vitro.
MECHANISMS UNDERLYING THE CARDIOVASCULAR ACTION OF A NEW DIHYDROPYRIDINE VASODILATOR, YC‐93
Authors: Satoh K. , Yanagisawa T. , Taira N.
Published: June 2007

1.The mechanisms underlying the cardiovascular action of YC‐93, a new dihydropyridine vasodilator with cyclic AMP phosphodiesterase inhibitory activity, was investigated by comparing its effects wth those of papaverine in various isolated, blood‐perfused heart preparations of the dog.

2. In all preparations YC‐93 injected into the nutrient arteries produced a dose‐dependent increase in blood flow, and in this respect YC‐93 was about twenty times more potent than papaverine on a weight basis.

3. In sinoatrial node preparations YC‐93 injected into the sinus node artery decreased sinus rate in a dose‐dependent manner, and in large doses produced atrial standstill.

4. In atrioventricular (a.v.) node preparations YC‐93 injected into the a.v. node artery increased a.v. conduction time in a dose‐dependent manner, and in large doses produced a second or third degree block of a.v. conduction. However YC‐93 injected into the anterior septal artery scarcely affected a.v. conduction.

5. In spontaneously contracting papillary muscle preparations YC‐93 injected into the anterior septal artery failed to affect ventricular automaticity in doses which markedly decreased developed tension of papillary muscles.

6. In papillary muscle preparations driven at a fixed rate YC‐93 injected into the anterior septal artery produced a dose‐dependent decrease in developed tension of papillary muscles.

7. Unlike YC‐93, papaverine decreased a.v. conduction time in a.v. node preparations and increased developed tension of papillary muscle preparations.

8. The cardiac effects of YC‐93 elucidated in the present experiments are characteristic of calcium‐antagonistic vasodilators. The action of YC‐93 as an inhibitor of cyclic AMP phosphodiesterase does not appear to play a role in its cardiac action.
ANGIOTENSIN, HYPOXIA, VERAPAMIL AND PULMONARY VESSELS
Authors: Suggett A. J. , Mohammed F. H. , Barer Gwenda R.
Published: June 2007

1. The action of angiotensin II on lung vessels was compared in dogs, cats, ferrets and rats using isolated perfused lungs and lobes of lungs perfused in vivo, both at constant flow, so that increases in inflow pressure at constant outflow pressure indicated increases in resistance.

2. Angiotensin II caused some increases in resistance in dogs, cats and rats but not ferrets. The increases were small compared with changes in the systemic circulation. Larger increases could be obtained in isolated lungs where there was no interference from rises in left atrial pressure.

3. All four species showed pulmonary vasoconstriction during hypoxia and ferret lungs were especially responsive. Thus angiotensin II cannot be the mediator of hypoxic vasoconstriction in all these species.

4. Angiotensin II significantly increased the response to hypoxia in isolated cat and rat lungs while also increasing baseline inflow pressure; the response to hypoxia was not altered in ferrets. Angiotensin II may therefore enhance reactivity of pulmonary vessels.

5. Verapamil, an inhibitor of calcium transport across cell membranes, reduced the response to hypoxia in rats and ferrets more than it reduced the response to angiotensin II in rats or prostaglandin F2α in ferrets. Thus hypoxic pulmonary vasoconstriction probably involves transport of calcium.
THE INFLUENCE OF DIBUTYRYL ADENOSINE CYCLIC MONOPHOSPHATE ON CELL PROLIFERATION IN THE EPITHELIUM OF THE JEJUNAL CRYPTS, THE COLONIC CRYPTS AND IN COLONIC CARCINOMATA OF RAT
Authors: Tutton P. J. M. , Barkla D. H.
Published: June 2007

1. Cell proliferation in the jejunal crypts, the colonic crypts and in dimethyl‐hydrazine (DMH)‐induced adenocarcinomata of rat colon was measured using a stathmokinetic technique.

2. Dibutryl cyclic adenosine monophosphate (dibutyryl cAMP) was found to inhibit cell proliferation in colonic crypts and in colonic adenocarcinomata.

3. Dibutryl cAMP at very high doses was found to inhibit jejunal crypt cell proliferation but at lower doses was found to accelerate jejunal crypt cell proliferation.

4. Neither bilateral adrenalectomy nor chemical sympathectomy was found to abolish the ability of dibutryl cAMP to stimulate jejunal crypt cell proliferation.

5. The present results are difficult to interpret in terms of known hormonal influences on cell proliferation in the tissues examined and of established actions, of these hormones on cyclic nucleotide metabolism in other tissues.