bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITORS CAPTOPRIL AND ENALAPRIL ON cAMP CONTENT OF SPECIFIC BRAIN AREAS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Geiger Helmut , Bahner Udo , Palkovits Miklós , Heidland August
Published: June 2007

1. The influence of two angiotensin‐converting enzyme inhibitors, captopril and enalapril, on the cAMP content of microdissected brain areas was examined in spontaneously hypertensive rats. Both drugs depleted systolic arterial blood pressure significantly.

2. Captopril and enalapril increased the level of cAMP in catecholaminergic cell groups in the lower brain‐stem. Captopril was more effective in the substantia nigra, while enalapril treatment resulted in high cAMP levels in the ventrolateral medulla oblongata (A1 catecholaminergic cell group).

3. Both drugs, especially captopril, depleted cAMP content in the cingulate cortex.

4. No changes in cAMP levels were measured in the primary baroreceptor centre (nucleus of the solitary tract) following either captopril or enalapril treatment.
NORADRENERGIC REINNERVATION OF THE RAT VAS DEFERENS AFTER VASOVASOSTOMY FOLLOWING VASECTOMY
Authors: DeGaris Richard M. , Pennefather Jocelyn N.
Published: June 2007

SUMMARY

1. Anastomosis (vasovasostomy) of epididymal and prostatic halves of vasa deferentia was carried out in rats in which unilateral or bilateral medial transection (vasectomy) had been performed 4 weeks previously.

2. Noradrenaline levels in epididymal halves of vasa deferentia, 8 weeks after anastomosis with prostatic halves, were approximately 40% of those in epididymal halves of contralateral, unoperated vasa deferentia. Catecholamine fluorescence was partially restored after anastomosis.

3. Responses of epididymal halves of transected vasa deferentia to electrical field stimulation (1 ms, 60 V, 10 pulses at 0.01–50 Hz) were partially restored 8 and 15 weeks after anastomosis.

4. Noradrenaline was equipotent in causing contraction of epididymal halves of unoperated and anastomosed vasa deferentia at 8 and 15 weeks after vasovasostomy. The ability of nisoxetine (0.1 μmol/l) to potentiate the effects of noradrenaline was partially restored by vas deferens repair.

5. Noradrenaline levels and neurotransmission in prostatic halves of vasa deferentia were relatively unaffected by vasectomy and subsequent vasovasostomy.

6. Fertility was restored 4–8 weeks after bilateral anastomosis performed in a group of eight rats 4 weeks after bilateral vasectomy.

7. These observations show that in the rat the noradrenergic denervation of the epididymal segment of the vas deferens after medial transection is partially reversible by anastomosis 4 weeks later, and that full noradrenergic reinnervation of the organ is not essential for the return of fertility after vasectomy and vasovasostomy in this species.
NEUROLOGICAL CONSEQUENCES OF MAGNESIUM DEFICIENCY: CORRELATIONS WITH EPILEPSY
Authors: Leaver D. D. , Parkinson G. B. , Schneider K. M.
Published: June 2007

SUMMARY

1. The plasma calcium and magnesium concentrations of sheep have been manipulated by feeding liquid diets with various calcium and magnesium concentrations.

2. When the magnesium status of the diet was low, both plasma calcium and magnesium concentrations declined, but the decline in calcium was much more rapid and extensive when the content of calcium in the diet was also low. This loss of calcium control in magnesium deficiency was attributed to end‐organ resistance to parathyroid hormone.

3. Correlation between plasma and CSF calcium and magnesium concentrations indicated that convulsions occurred when CSF magnesium and plasma calcium concentrations declined.

4. The neurological mechanisms likely to be responsible for the induction of these convulsions are discussed and the factors precipitating convulsions in magnesium deficiency and epilepsy are compared.
MODULATION OF NORADRENALINE RELEASE IN VIVO THROUGH PREJUNCTIONAL α‐ADRENOCEPTORS
Authors: Majewski H.
Published: June 2007

SUMMARY

1. Extensive in vitro studies have suggested that noradrenaline release from sympathetic nerve endings is modulated by α2‐adrenoceptors on the terminal varicosities, activation of which by α‐adrenoceptor agonists or neuronally released noradrenaline leads to inhibition of transmitter release.

2. Studies in intact animals support essentially the physiological operation of this mechanism, whereas human studies have reached mixed conclusions and more information is required.
EXTRACTION OF NEUROTENSIN BY THE LIVER
Authors: Brook Christopher W. , Shulkes Arthur , Sewell Richard B. , Smallwood Richard A.
Published: June 2007

1. Neurotensin is released from the intestine into the portal circulation and to exert a systemic effect it must traverse the liver intact.

2. The role of the liver in neurotensin clearance was examined using the isolated perfused rat liver preparation. Two concentrations of neurotensin were used to determine the extraction capacity of the liver.

3. Approximately 10% of the added neurotensin (with either dose) was extracted in a single pass through the liver. This extraction rate was low when compared to previous studies with cholecystokinin (60% extraction in a single pass) and vasoactive intestinal peptide (100%).

4. It is concluded that there is a small but high capacity for direct extraction of neurotensin. This low direct extraction percentage supports our previous contention that the major influence of the liver on the metabolism of neurotensin is by the release of neurotensin degrading peptidases into the circulation.
RITANSERIN AND SEROTONERGIC MECHANISMS IN BLOOD PRESSURE AND FLUID REGULATION IN SHEEP
Authors: Nelson M. , Coghlan J. P. , Denton D. A. , Tresham J. J. , Whitworth J. A. , Scoggins B. A.
Published: June 2007

1. In previous studies, exogenous serotonin (5‐HT), administered intravenously, caused dose‐related increases in mean arterial pressure and heart rate in conscious sheep. The 5‐HT2 antagonist ketanserin (0.1 mg/kg per h, i.v.) was shown to lower blood pressure in the conscious sheep primarily through antagonism of α‐adrenoceptors.

2. A newer 5‐HT2 antagonist, ritanserin, is a more selective antagonist in vivo, as it attenuated or abolished pressor responses to exogenous 5‐HT, but not to phenylephrine.

3. When infused alone, ritanserin (0.1 mg/kg per h, i.v.) failed to produce a decrease in blood pressure, suggesting that 5‐HT antagonistic properties are not sufficient by themselves to lower blood pressure.

4. Ritanserin displayed a different metabolic profile to ketanserin, with a markedly decreased water intake. The mechanism of this effect is unresolved, but may imply a permissive role for 5‐HT in the modulation of drinking responses in the sheep.

5. Ritanserin did not modify ACTH‐induced hypertension in sheep.
REPRODUCIBILITY OF PRESSOR RESPONSE TO HANDGRIP: INFLUENCE OF TIME INTERVALS, STRENGTH AND DURATION OF EXERCISE
Authors: Costa F. V. , Borghi C. , Mussi A. , Ambrosioni E.
Published: June 2007

1. The reproducibility of pressor response to handgrip performed at different time intervals and with different combinations of the product duration × strength of the exercise was evaluated in 14 normotensive subjects recording blood pressure with a non‐invasive automatic device.

2. Subjects underwent five consecutive tests (30% of maximal voluntary contraction × 90 s) at 30 min, and 24 h intervals and repeated the test after 12 months. Furthermore, they underwent at 24 h intervals a randomized sequence of handgrip tests whose product strength × duration was combined in order to achieve either a constant or an increasing level of exercise.

3. Blood pressure response to exercise performed at 30 min intervals was much less reproducible than that induced by handgrip performed at time intervals ≥ 24 h.

4. Increasing gradually the product strength × duration of the handgrip test there was a proportional blood pressure increase, whereas when the product was maintained constant diastolic blood pressure increase was also constant and reproducible within each subject.

5. This study shows that it is possible to obtain reproducible diastolic blood pressure responses to handgrip test measuring blood pressure with a non‐invasive automatic device when the tests are performed at a time interval of at least 24 h. The choice of the strength and of the duration of the exercise is very important for the reproducibility of the test.
THE EFFECT OF OXYTOCIN ON PORCINE MALIGNANT HYPERPYREXIA SUSCEPTIBLE SKELETAL MUSCLE
Authors: Sim A. T. R. , White M. D. , Denborough M. A.
Published: June 2007

1. Certain commercial preparations of oxytocin have been reported to reverse the development of pale soft exudative meat and malignant hyperpyrexia (MH) in pigs in vitro.

2. In this study it is shown that preservative‐free oxytocin has no significant effect on the characteristic contractures of MH susceptible (MHS) muscle to halothane, caffeine, succinylcholine and KCl in vitro.

3. Whilst a commercial preparation of oxytocin, Syntocinon (containing chlorbutol as preservative), reversed and prevented the MHS characteristic responses, this study demonstrates conclusively that this was entirely due to the preservative chlorbutol.
EFFECTS OF NEUROPEPTIDE Y ON THE PRESSOR RESPONSES TO PHENYLEPHRINE AND TO ACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM IN ANAESTHETIZED RATS
Authors: Revington Maureen L. , McCloskey D. I. , Potter Erica K.
Published: June 2007

1. The effects of neuropeptide Y (NPY) on the pressor responses to intravenous injections of phenylephrine and to reflex activation of the sympathetic nervous system by stimulation of the sciatic nerve were examined in anaesthetized rats.

2. NPY (10–20 μg/kg) always potentiated the pressor response to exogenous phenylephrine (by a mean of 28.1 ± 5.0%). The effect of the same dose of NPY on the pressor response to sciatic nerve stimulation was variable (sometimes inhibition, sometimes potentiation).

3. NPY appears to act by potentiating post‐synaptic a‐adrenoceptor‐mediated vasoconstrictor effects. It may also inhibit noradrenaline release by a presynaptic action. Thus the net effect of NPY on sympathetic activation in vivo may depend on the balance between these two opposing actions.
EFFECTS OF THE OPIOID PEPTIDES [MET5]ENKEPHALIN‐ARG6‐PHE7 AND [MET5]ENKEPHALIN‐ARG6‐GLY7‐LEU8 ON CHOLINERGIC NEUROTRANSMISSION IN THE RABBIT ISOLATED ATRIA
Authors: Wong‐Dusting H. , Rand M. J.
Published: June 2007

1. The effect of the opioid peptides [Met5]enkephalin‐Arg6‐Phe7 (MEAP) and [Met5]enkephalin‐Arg6‐Gly7‐Leu8 (MEAGL) were compared with those of [Leu5]enkephalin and [d‐Ala2, Met5]enkephalinamide (DAME) on cholinergic neuro‐transmission in the rabbit isolated atria.

2. Rabbit isolated atria had a resting rate of 190 beats/min. In the presence of the β‐adrenoceptor antagonist propranolol (0.3 μmol/l), atria responded to electrical field stimulation with a cholinergically mediated negative chronotropic response. The opioid peptides had no effect on the resting rate, but inhibited the negative chronotropic response to field stimulation. The IC50 values for inhibiting the cholinergic responses were 1.4 μmol/l for [Leu5]enkephalin (LE), 1.4 μmol/l for MEAP, 1.3 μmol/l for MEAGL and 0.2 μmol/l for DAME. Responses of a similar magnitude to exogenous acetylcholine were unaffected.

3. Thus, MEAP, MEAGL and LE had similar potencies but DAME was about seven times more potent in inhibiting cholinergic neurotransmission in the rabbit isolated atria. The site of inhibition appears to be prejunctional.
HAEMODYNAMIC AND METABOLIC RESPONSES OF LABORATORY RABBITS TO NEAR‐MAXIMAL TREADMILL EXERCISE
Authors: Jover Bernard , McGrath Barry P. , Ludbrook John
Published: June 2007

1. The haemodynamic and metabolic responses of four laboratory rabbits to horizontal treadmill exercise at 8, 12, 16 and 20 m/min were studied. The primary haemodynamic variables measured were heart rate, cardiac output and arterial pressure. The metabolic variables measured were arteriovenous oxygen difference, whole‐body oxygen consumption and central venous plasma lactate concentration.

2. Only at 8 m/min did the haemodynamic and metabolic variables reach an approximate steady state. This was the greatest speed at whichaerobic exercise could be sustained for 4 min in all rabbits.

3. As the speed of the treadmill was increased the rabbits showed signs of exhaustion after progressively shorter periods of exercise. Exhaustion was associated with steep rises in central venous plasma lactate concentration. Exhaustion was also usually associated with secondary rises in systemic vascular resistance and arterial pressure, especially at 20 m/min.

4. The asymptotic (maximal) values for heart rate, cardiac index and O2 consumption were 386 beats/min, 263 ml/kg per min and 21.7 ml/kg per min, respectively.

heart do not permit it to run continuously at other than a slow rate. Exhaustion is associated with increasing oxygen debt and, especially at near‐maximal rates of exercise, with intense vasoconstriction in as yet unidentified vascular beds.
AMITRIPTYLINE ACTION ON SYMPATHETIC NEURONAL FUNCTION IN DEPRESSED WOMEN
Authors: Corona G. L. , Cucchi M. L. , Frattini P. , Santagostino G. , Schinelli S. , Tosca P. , Savoldi F. , Zerbi F.
Published: June 2007

1. Noradrenaline plasma levels and cardiovascular function modifications with orthostatic challenge during therapy were studied in 59 female depressed inpatients treated with 100 mg amitriptyline daily by intramuscular route for 4 weeks.

2. Therapy induced an increase in pulse rate in supine and upright positions, a decrease of noradrenaline levels and modified standing systolic and (partially) diastolic blood pressure, particularly in elderly subjects.

3. No correlation between neurotransmitter or functional changes and drug plasma levels was noted.

4. The supposed lower noradrenergic output together with blood pressure drop in both positions suggests a reduced sympathetic tone.
POTASSIUM CONTRACTURES IN THE MOUSE DIAPHRAGM: REGIONAL VARIATION IN THE MULTIPHASIC RESPONSE
Authors: Singh Yadhu N. , Dryden William F.
Published: June 2007

SUMMARY

1. Submaximal potassium‐induced contractures were studied in isolated mouse hemidiaphragms (HD) and compared with extensor digitorum longus (EDL) and soleus.

2. In the HD, the contracture was triphasic: an initial small, fast phase followed by a larger slow phase, and a late phase which was seen on prolonged exposure.

3. Costal segments of the HD responded to elevated potassium with a larger fast phase, while dorsal or ventral segments produced a larger slow phase.

4. In calcium‐free solution, the fast phase appeared to be unaffected, while the slow phase was potentiated and its time course abbreviated. The late phase was greatly attenuated or abolished.

5. In the soleus, but not the EDL muscle, contracture amplitude in calcium‐free solution was potentiated and the time course was shortened.

6. The characteristics of potassium‐induced contractures of both the soleus and EDL muscles are to be seen in the response of the hemidiaphragm, but there is a regional variation in their proportional contribution which suggests a heterogeneity in diaphragm composition.
THE EFFECT OF SMOKING ON CAFFEINE ELIMINATION: IMPLICATIONS FOR ITS USE AS A SEMIQUANTITATIVE TEST OF LIVER FUNCTION
Authors: Murphy Therese L. , McIvor Carolyn , Yap A. , Cooksley W. G. E. , Halliday June W. , Powell L. W.
Published: June 2007

1. The effects of caffeine ingestion and cigarette smoking on caffeine and antipyrine pharmacokinetics were studied using normal subjects as their own controls before and after cessation of smoking in an attempt to minimize genetic and other environmental influences.

2. Moderate caffeine ingestion had no inducing effect on caffeine or antipyrine clearance.

3. Cessation of cigarette smoking significantly reduced clearance of caffeine and antipyrine.

4. These results demonstrate that cigarette smoking significantly affects caffeine pharmacokinetics and this may contribute to the variable results for caffeine kinetics found in patients with liver disease.
DISTRIBUTION OF CADMIUM IN BODY ORGANS AND HEPATIC METALLOTHIONEIN CONTENT FOLLOWING CHELATION THERAPY
Authors: Tewari Prakash C. , Flora Swaran J. S. , Tandon Sushil K.
Published: June 2007

1. Calcium trisodium diethylene triamine penta‐acetate (CaNa3DTPA), sodium 1,2 diaminocyclohexane tetra‐acetate (Na2CDTA), triethylenetetramine hydrochloride (TETA. HCl) and sodium diethyldithiocarbamate (NaDDC) were investigated for their efficacy to mobilize cadmium (Cd) from various tissues and hepatic metallothionein (MT) in Cd‐exposed rats.

2. All chelating agents reduced the hepatic Cd burden but did not elicit any influence on other tissues, except that TETA. HCl lowered pancreas Cd and NaDDC increased brain Cd.

3. Cadmium‐induced hepatic MT was lowered upon treatment with CaNa3DTPA while it increased further following treatment with NaDDC.

4. The chelating agents, in split doses, are capable of reducing the hepatic burden of Cd and altering the hepatic MT level.

5. While all the chelating agents decreased Cu content of hepatic MT, only CaNa3DTPA decreased its Zn content and TETA. HCl mobilized MT‐bound Cd.

6. The administration of chelating agents alone in normal animals showed that NaDDC induced greater hepatic MT synthesis and increased MT‐bound Zn than other chelating agents.
DISPOSITION OF PHENYTOIN AND PHENOBARBITONE IN THE ISOLATED PERFUSED HUMAN PLACENTA
Authors: Kluck R. M. , Cannell G. R. , Hooper W. D. , Eadie M. J. , Dickinson R. G.
Published: June 2007

b

1. The disposition of the anti‐epileptic agents phenytoin (PHT) and pheno‐barbitone (PB) was investigated in lobules of term human placentae perfused using separate maternal and fetal circulations for 6 h periods.

2. No evidence for metabolism of PHT or PB to their p‐hydroxylated or other derivatives was found either in perfused lobules or by incubation with placental microsomes.

3. Both PHT and PB were readily transferred across the placenta after administration to either the maternal or fetal perfusates.

4. PHT, unlike PB, showed considerable accumulation in placental tissue.
MINERALOCORTICOIDS ARE NOT INVOLVED IN THE ANTIHYPERTENSIVE EFFECT OF NEONATAL THYMECTOMY IN THE GENETICALLY HYPERTENSIVE LH RAT
Authors: Bataillard Alain , Gomez‐Sanchez Celso E. , Vincent Madeleine , Touraine Jean‐Louis , Sassard Jean
Published: June 2007

SUMMARY

1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hypertensive (LH), normotensive (LN) and low‐blood pressure (LL) rats of the Lyon strain. Sham‐operated animals served as controls.

2. Neonatal thymectomy prevented the spontaneous increase of SBP in LH rats while it slightly decreased the SBP of LN and did not change that of LL rats.

3. Five week old sham‐operated LH rats exhibited an increased urinary excretion of DOC and a decreased excretion of B compared with both LN and LL controls. Thymectomy did not alter the urinary excretion of adrenal steroids in LN and LL rats. The urinary excretion of B was markedly enhanced in thymectomized LH rats whereas that of DOC remained unmodified.

4. These data suggested that the thymus could be involved in the development of hypertension in LH rats.

5. The antihypertensive effect of thymectomy did not seem to be mediated by a decreased mineralocorticoid production in the genetically hypertensive rat of the Lyon strain.
OXIDATION PHENOTYPING IN CHINESE AND MALAY POPULATIONS
Authors: Lee Edmund J.D. , Nam Yeoh Peng , Hee Gong Ngie
Published: June 2007

SUMMARY

1. Debrisoquine hydroxylation phenotyping was carried out in 97 Chinese and 97 Malay healthy volunteers.

2. No poor metabolizer was found in the Chinese population. Using a metabolic ratio antimode of 10.0, two poor metabolizers were present amongst the Malays studied.
CAFFEINE‐AND POTASSIUM‐INDUCED CONTRACTURES OF MOUSE ISOLATED SOLEUS MUSCLE: EFFECTS OF VERAPAMIL, MANGANESE, EGTA AND CALCIUM WITHDRAWAL
Authors: Savage A. O. , Atanga K. G.
Published: June 2007

1. The effects of verapamil, manganese, EGTA and Ca2+‐withdrawal on caffeine and potassium‐induced contractures of the mouse isolated soleus muscle have been studied. All four treatments profoundly inhibited, in concentration‐dependent manner, both K+‐and caffeine‐induced contractures, and recovery from these treatments was slight.

2. Caffeine (5.14–51.4 mmol/1), elicited biphasic contractures, characterized by an initial phasic, and subsequent tonic contractures. K+‐induced contractures were monophasic except at the higher concentrations (53.4–214 mmol/1), when biphasic responses were also recorded. The biphasic K+ contracture had a time course similar to the caffeine‐induced response.

3. Both phases of the caffeine and K+ responses were abolished by the introduction of CA2+‐free Krebs'‐Henseleit solution (KHS). Increasing [Ca2+]o from 1 to 5 mmol/1, markedly inhibited the amplitude of caffeine and K+ contractures.

4. In high [K+]o KHS, peak contractures to caffeine were reduced to about 50% of those in normal KHS. In the presence of 15.4 mmol/1 caffeine, the responses to lower concentrations of K+ (13.4–26.8 mmol/1) increased, while responses evoked by the higher K+ concentrations were depressed compared with controls in normal KHS.

5. Pancuronium or d‐tubocurarine severely inhibited caffeine‐induced contractures, but only slightly inhibited K+‐induced responses.

6. It is suggested that both caffeine‐and K+‐induced contractures of the mouse soleus are dependent upon the presence of [CA2+]o, and that these contractures possibly occurred as a result of extracellular Ca2+‐influx.
BOOK REVIEW
Authors: DANKS DAVID M.
Published: June 2007

Cellular and Molecular Basis of Cystic Fibrosis. By G. Mastella and P. N. Quinton. Pages xi + 487, illustrated. San Francisco Press Inc., San Francisco 1988. US $40.00.
EFFECT OF ANTIHYPERTENSIVE THERAPY ON THE CARDIOVASCULAR AMPLIFIERS
Authors: Korner P. I. , Adams M. A. , Jennings G. L. , Bobik A.
Published: June 2007

1. In established chronic hypertension the amplifier properties of vessels and heart contribute about 70% to the maintenance of the elevated blood pressure (BP). Recent studies in spontaneously hypertensive rats (SHR) suggest that the structural changes occur very early and their amplifier properties may be critical for the development of hypertension.

2. In patients with primary hypertension, the greater the regression of cardiac and vascular hypertrophy, the slower the subsequent redevelopment of hypertension. Following regression of hypertrophy, the antihypertensive action of moderate regular exercise can maintain BP in the normal range in a proportion of patients.

3. Early treatment of SHR with enalapril greatly reduces the subsequent ‘steady‐state’ BP in SHR. This produces virtually complete regression of vascular hypertrophy, but somewhat lesser degrees of regression of cardiac hypertrophy.

4. These studies serve as models for primary and secondary prevention of hypertension. A strategy based on intermittent drug and non‐pharmacological therapy in man may contribute to the secondary prevention of atherosclerosis, in view of the adverse effects on lipid profiles of many antihypertensive drugs.
EFFECTS OF ANTIHYPERTENSIVE DRUGS ON CARDIOVASCULAR RISK FACTORS
Authors: Howes L. G. , Louis W. J.
Published: June 2007

1. Large scale studies have failed to show a substantial benefit of antihypertensive therapy on the incidence of ischaemic heart disease.

2. This may be due to adverse effects of antihypertensive drugs on plasma lipoproteins or because of failure to adequately manage other risk factors for atherogenesis.

3. Hypercholesterolaemia is very common in patients receiving antihypertensive therapy, and is difficult to manage successfully using existing treatment strategies.

4. The achievement of a reduction in mortality and morbidity from ischaemic heart disease amongst hypertensive patients represents a major challenge. Success will probably depend upon the development of adequate methods of lowering plasma cholesterol levels.
AN UNUSUAL PHOSPHATIDYLINOSITOL TURNOVER PATHWAY IN NORADRENALINE‐PERFUSED RAT HEARTS
Authors: Woodcock Elizabeth A. , Smith A. Ian , Wallace Catherine A. , White L. Barbara Schmauk
Published: June 2007

1. The phosphatidylinositol turnover pathway has been studied in noradrenaline‐perfused rat hearts using anion‐exchange high performance liquid chromatography.

2. The active calcium‐releasing compound inositol‐(1,4,5)trisphosphate was detected together with its degradation products inositol‐(1,4)bisphosphate and inositol monophosphate. All these products increased in response to noradrenaline stimulation.

3. At noradrenaline perfusion times from 5 s to 20 min there was no appearance of inositol‐(1,3,4,5)tetrakisphosphate or its degradation products: inositol‐(1,3,4)trisphosphate or inositol‐(1,3) and (3,4)bisphosphates.

4. These data suggest the absence of the inositol‐(1,4,5)trisphosphate phosphorylation/dephosphorylation pathway in heart.
AN APPRAISAL OF THE EFFECTS OF USUAL VS RECENT ALCOHOL INTAKE ON BLOOD PRESSURE
Authors: Puddey I. B. , Jenner D. A. , Beilin L. J. , Vandongen R.
Published: June 2007

1. In a population‐based study of 343 men from two public utilities, 260 subjects reported drinking alcohol at least once a week. In these subjects a comparison was made of the relative effects on blood pressure of either their usual alcohol intake (assessed from a 7‐day retrospective diary) or recent alcohol intake (alcohol consumed at the last drinking session in the 24 h prior to blood pressure measurement).

2. Both usual and recent alcohol intake showed similar correlations with level of blood pressure (BP). After adjustment of BP for the potential confounding influences of body mass index, age and smoking status, systolic and diastolic BP remained highest in those subjects with the highest reported levels of both usual and recent alcohol intake.

3. In regression analyses comprising only those subjects who reported drinking in the 24 h before BP measurement, a 3–4 fold greater effect of usual rather than recent intake on both systolic and diastolic BP was predicted from the b coefficients. Regression analysis also demonstrated that the relationship between usual alcohol intake and BP was independent of recent intake, while the relationship between recent intake and BP was no longer significant when usual alcohol intake was entered into the regression equation.

4. These observations suggest that consistent regular drinking is a more important determinant of the alcohol/BP relationship than intake in the previous 24 h.
EFFECT OF PURE EICOSAPENTAENOIC ACID FEEDING ON BLOOD PRESSURE AND VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yin K. , Croft K. D. , Beilin L. J.
Published: June 2007

1. This study examined the effects of eicosapentaenoic acid (EPA) treatment on vascular reactivity and blood pressure in spontaneously hypertensive rats (SHR).

2. Twenty SHR were given pure EPA as the methyl ester (280 mg/kg) by gavage for 10 days. An equal number of control rats received vehicle alone. EPA treatment had no effect on blood pressure compared with control rats.

3. Aortic rings from EPA‐treated rats, precontracted with PGF2α showed increased endothelium‐dependent relaxations to acetylcholine. Endothelium‐independent relaxations to sodium nitroprusside were not altered. Rings from rats fed pure EPA did not show any differences in vasoconstrictor responses to noradrenaline or serotonin.

4. Serum thromboxane B2 (TXB2) levels fell 17% in animals given pure EPA, but prostacyclin production was not affected. These responses are less than those seen following Max EPA fish oil.

5. Thus, pure EPA treatment did not lower blood pressure, but may have a direct effect on aortic endothelia and cause increased endothelium‐dependent relaxations in response to acetylcholine in SHR.
A TWO‐SITE MONOCLONAL IMMUNORADIOMETRIC ASSAY FOR TOTAL RENIN PROTEIN: COMPARISON WITH AN ESTABLISHED ENZYME KINETIC ASSAY
Authors: Thatcher Robin L. , Whitworth Judith A. , Casley David G. , Johnston Colin I. , Skinner Sandford L.
Published: June 2007

1. A two‐site monoclonal immunoradiometric assay (IRMA) for total renin protein was established to cover the range 0.3–300 μiu. The limit of sensitivity was 2 μiu/ml plasma.

2. IRMA after acid activation of plasma prorenin gave the highest and most consistent values for total plasma renin (TPRC = 197 μiu/ml, s.e.m. = 22, in 17 normal adults). In untreated plasma, TPRC measured by IRMA was lower than expected, but in amniotic fluid expected values were obtained.

3. Human angiotensinogen at normal concentrations did not interfere with binding of renin to the first antibody, but ovine angiotensinogen displaced the standard curve significantly.

4. TPRC measured by IRMA is convenient and highly sensitive, but either the state of activation of the enzyme or another effect of acidification of plasma influences the estimated value.

5. Active renal renin may not be the appropriate reference standard for this IRMA unless plasma renin is previously activated.
ALTERING ANGIOTENSIN LEVELS BY ADMINISTRATION OF CAPTOPRIL OR INDOMETHACIN, OR BY ANGIOTENSIN INFUSION, CONTRIBUTES TO AN UNDERSTANDING OF ATRIAL NATRIURETIC PEPTIDE REGULATION IN MAN
Authors: Klemm Shelley A. , Gordon Richard D. , Tunny Terry J. , Hamlet Stephen M.
Published: June 2007

1. Plasma atrial natriuretic peptide (ANP) levels were positively correlated with plasma renin activity (PRA) levels, when blood volume and blood pressure (BP) were not raised in normal subjects (NLS) or patients with postoperative aldosterone‐producing adenoma (APA), Bartter's syndrome (BS), Addison's disease, anorexia nervosa, diuretic abuse or salt‐losing congenital adrenal hyperplasia.

2. Angiotensin II infusion raised ANP levels in NLS, and patients with BS, pre‐ and postoperative APA, only when BP rose, suggesting that this effect might be mediated by the rise in BP.

3. Captopril lowered aldosterone and ANP levels in renal artery stenosis, but falling BP levels could mediate this effect. Captopril lowered aldosterone and BP in BS, but did not lower ANP, perhaps because angiotensin remained elevated.

4. Indomethacin lowered ANP when PRA was initially normal or raised (NLS and BS), but not when PRA was suppressed (APA). This effect could not be mediated by BP, which rose, but could be mediated by renin‐angiotensin, which fell.

5. Factors other than central blood volume and atrial stretch may modulate ANP levels. Plasma angiotensin II may be such a factor, and may exert an important influence at high levels, especially when blood volume is low.
THERMOGENESIS AND THE EFFECT OF INJECTED CATECHOLAMINES ON THE OXYGEN CONSUMPTION OF CAFETERIA‐FED RATS
Authors: Maxwell G. M. , Nobbs S. , Bates D. J. , Fourie F.
Published: June 2007

1. The oxygen consumption (V̇o2):) of unrestrained rats given a ‘cafeteria’ (high energy, high fat) or control diet was studied. The resting values of V̇o2 were the same in each dietary group, whether maintained at 26°C or 6°C. This negative finding suggests that cafeteria feeding is not an important cause of diet‐induced thermogenesis (DIT).

2. The response of each group of rats to injected noradrenaline or dopamine was also studied. Each catecholamine could increase V̇o2 values but the response was much less in cold‐adapted rats measured at 6°C. In all experimental circumstances the dopamine response exceeded that of noradrenaline. There was no evidence that the cafeteria diet consistently increased the response to either catecholamine.

3. These results suggest that DIT cannot be equated with non‐shivering thermogenesis (NST). Furthermore, it is suggested that dopamine would be a better agent for measuring the oxygen equivalent of NST, since it would stimulate the dopamine receptors as well as the α‐ and β‐adrenoreceptors of brown fat.
BOOK REVIEWS
Authors: MORGAN TREFOR
Published: June 2007

Modern Techniques of Ion Transport. Edited by B. Brenner and J.H. Stein. Churchill Livingstone, New York, 1987. $126.00.

The Chance of a LCJetime: lifcriility and IVF. By Carol Dettmann and Douglas Saunders. Pages xiv + 224. Illustrated. Penguin Books, Ringwood, 1987. $14.95.
SHORT COMMUNICATION: EFFECTS OF VASOACTIVE INTESTINAL POLYPEPTIDE INFUSIONS ON RENAL FUNCTION IN PATIENTS WITH LIVER DISEASE
Authors: Calam J. , Unwin R. J. , Dorudi S. , Taylor C. , Springer C. J. , Peart W. S.
Published: June 2007

1. The effect of intravenous vasoactive intestinal peptide (VIP, 6 pmol/kg per min) on renal function in six patients with cirrhosis of the liver was examined.

2. VIP caused generalized vasodilation and increased plasma renin activity, but diminished the glomerular filtration rate by about one third.

3. The excretion of water, sodium, potassium and calcium also fell significantly.

4. These results differ from our findings in normal man in whom VIP diminished water and electrolyte secretion largely by increasing tubular reabsorption.

5. It is concluded that the elevated VIP levels present in patients with severe liver disease may affect renal function, but that the presence of liver disease may affect renal responses to VIP.
EFFECT OF DIPYRIDAMOLE ON BLOOD GLUCOSE AND LIVER CYCLIC AMP LEVELS AND PLATELET COUNT DURING ENDOTOXAEMIA IN MICE
Authors: Al‐Jibouri Layla M. , Najim Rafid A.
Published: June 2007

1. Blood glucose, liver cyclic AMP (cAMP) levels, and platelet count were studied at different times during a 12 h interval after intravenous (i.v.) endotoxin injection (40 mg/kg) in mice.

2. Blood glucose and liver cAMP levels showed a progressive decrease in endotoxic mice and the decrease was significant after 8 and 12 h.

3. Dipyridamole (50 mg/kg) administered intraperitoneally (i.p.) 7 h post‐endotoxin improved blood glucose and liver cAMP levels.

4. Platelet counts were decreased after 1 h in endotoxic mice and remained decreased up to 8 h. Dipyridamole administered soon after endotoxin improved platelet counts in endotoxic mice and increased survival rate to 100%.
RENAL EFFECTS OF ATRIAL NATRIURETIC FACTOR (99–126) IN CONSCIOUS SODIUM‐REPLETE SHEEP
Authors: Yates Neale A. , McDougall John G. , Coghlan John P. , Coker Andrew R. , Gibson Angela P. , Scoggins Bruce A.
Published: June 2007

1. The effect of renal arterial infusion of synthetic human atrial natriuretic factor (ANF(99–126)) on renal function in the conscious euvolaemic sheep was characterized. ANF (99–126) was infused for 2 h at 5 and 50 μg/h into the renal artery of crossbred Merino ewes with chronically indwelling cannulae inserted in the renal artery. The effect on absolute and fractional excretion of Na, K, Ca, Cl and HCO3, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and free water clearance (CH2O) were measured.

2. Infusion at 50 μg/h produced a fourfold increase in Na and Cl excretion. Ca excretion increased eightfold, while K and HCO3 increased by small amounts. At the lower dose only Na, Cl and Ca excretion increased significantly. The changes in absolute excretion of each ion were closely mirrored by changes in fractional excretion. CH2O became more negative at both levels of infusion. Small changes in GFR were measured at both rates of infusion. No changes in ERPF or renin secretion were observed.

3. ANF (99–126) infusion at 50 μg/h for 1 h increased the excretion of Li, such that more than 70% of the change in Na excretion was associated with the changes in Li clearance. Changes in GFR accounted for less than 10% of change in Na excretion.

4. Following either long‐term (50 μg/h for 6 h) or repeated short‐term (20 μg/h for 30 min) infusions of ANF (99–126), the response of Na excretion was not sustained. The mechanisms of the tachyphylaxis remains undetermined.

5. ANF (99–126) is a powerful stimulus to the absolute and fractional excretion of Na, K, Ca, Cl and HCO3. The mechanism of action is not known, but appears to be related to changes in tubular function and/or a change in glomerulotubular balance.
IONIC MECHANISMS UNDERLYING ACTION POTENTIALS IN MYOMETRIUM
Authors: Parkington H. C. , Coleman H. A.
Published: June 2007

1. The ionic mechanisms underlying the simple spike action potential in longitudinal myometrium of pregnant rats and the complex action potential which occurs in the same layer of pregnant guinea‐pigs are discussed.

2. The current during the upstroke of the simple spike is carried by calcium and repolarization results from inactivation of the calcium current and activation of a potassium current.

3. A slow inward current underlies the plateau component of the complex action potential and calcium is involved in carrying or regulating this current.

4. Single channel recordings from the longitudinal myometrium of pregnant guinea‐pigs reveal large conductance (130–170 pS) potassium channels which are activated by depolarization of the membrane. The activation of these channels during the upstroke of the spike would contribute to the rapid termination of the spike.

5. The duration of the plateau component of the complex action potential closely correlates with the duration of contraction and it is suggested that sufficient calcium may enter the cell during the action potential to activate the contractile apparatus directly.
β‐ADRENOCEPTORS IN CIRCULAR AND LONGITUDINAL MYOMETRIAL MEMBRANES AND IN LUNG MEMBRANES FROM DIOESTROUS AND POST‐PARTUM GUINEA‐PIGS
Authors: Handberg Gwynneth M. , Davis Elizabeth A. , Hall Solveiga , Molenaar Peter , Summers Roger J. , Pennefather Jocelyn N.
Published: June 2007

1. We have examined the binding of (—)[125I]‐cyanopindolol ((—)[125I]‐CYP) to membranes prepared from uterus and lung of dioestrous and post‐partum (1–6 days) guinea‐pigs.

2. The densities of β‐adrenoceptor binding sites in circular and longitudinal myometrium from dioestrous animals were similar, and approximately one‐eighth of those in the lung. Ascorbate and ethylenediaminetetraacetic acid in the incubation medium did not affect binding.

3. The numbers and affinities of β‐adrenoceptor binding sites in both myometrial layers and in lung parenchyma from post‐partum animals were similar to those in corresponding tissues from dioestrous animals.

4. The distribution of β‐adrenoceptor binding sites in the post‐partum uterus was examined using receptor autoradiography. Binding to circular and longitudinal muscle layers and to the endometrium was inhibited by (—)‐propranolol (1 μmol/l), by the β2‐adrenoceptor selective antagonist ICI 118,551 (70 nmol/l), but not by the β1‐adrenoceptor selective antagonist CGP 20712A (100 nmol/l), indicating that the β‐adrenoceptor present was of the β2‐subtype.

5. The ability of isoprenaline to compete for (—)[125I]‐CYP binding sites in uterine membranes from post‐partum animals was approximately twice that in corresponding preparations from dioestrous animals.

6. Changes in the numbers or affinity of β2‐adrenoceptors cannot account for the marked and selective enhancement of the actions of sympathomimetic amines at β‐adrenoceptors previously observed in longitudinal myometrium taken from post‐partum guinea‐pigs. It is suggested that enhancement of later steps in the chain of events between β‐adrenoceptor occupancy and uterine relaxation, and/or a decrease in the contribution of α‐adrenoceptors to the net effect of the amine might provide alternative explanations.
EFFECTS OF ADRENALINE, ISOPRENALINE AND FORSKOLIN ON PREGNANT HUMAN MYOMETRIAL PREPARATIONS
Authors: Story Margot E. , Hall Solveiga , Ziccone Sebastian P. , Paull John D.
Published: June 2007

1. The effects of adrenaline, isoprenaline and forskolin upon the evoked contractions of field‐stimulated preparations of human, pregnant, isolated myometrium have been examined. Specimens were obtained at lower segment Caesarean section from patients at 31 (n= 1) and 36–40 (n= 10) weeks of gestation.

2. Adrenaline enhanced the electrically evoked contractions of all preparations studied, indicating that its predominant action on these pregnant myometrial tissues was at α‐and not β‐adrenoceptors.

3. Isoprenaline in concentrations at and below 10 μmol/1 produced inhibitory effects in eight of 11 experiments. In the remaining three experiments, tissues were not responsive to the inhibitory effects of isoprenaline.

4. In all preparations exposed to higher concentrations of isoprenaline (30 or 100 μmol/1), its effects were excitatory.

5. Forskolin produced inhibitory effects on preparations from all uteri, including those from which tissues unresponsive to isoprenaline had been obtained.

6. It is suggested that forskolin in the concentrations which were effective in this study produced its inhibitory effects largely through activation of adenylate cyclase. This implies that the lack of an inhibitory response of some preparations to isoprenaline was not due to reduced activity of the adenylate cyclase system, but that the failure of isoprenaline to produce an inhibitory effect could be due to diminished numbers of β‐adrenoceptors and/or increased numbers of α‐adrenoceptors, or to a defect in the coupling of the receptors to the adenylate cyclase system. Alternatively, the presence of an endogenous antagonist of the effects of isoprenaline (for example, an eicosanoid), could mask its inhibitory effects.

7. The absence of an inhibitory effect of isoprenaline on some specimens of human gravid myometrium could have clinical implications, in view of the widespread use of β2‐adrenoceptor agonists as uterine relaxants.
EFFECTS OF RENAL DENERVATION AND ATRIAL NATRIURETIC FACTOR ON TUBULAR REABSORPTION IN ANAESTHETIZED RATS
Authors: Dowling G. J. , Harris P. J. , Skinner S. L.
Published: June 2007

1. The effects of acute unilateral renal denervation were examined in 17 anaesthetized rats. Renal haemodynamic changes were monitored using standard clearance techniques. Lithium clearance was used to assess fractional proximal sodium and water reabsorption.

2. Denervation resulted in ipsilateral renal vasodilatation with marked natriuresis and diuresis, a small increase (15%, P < 0.05) in glomerular filtration rate (GFR) and a consequent reduction in filtration fraction. Fractional lithium reabsorption decreased (67.3 ± 2.9% to 54.5 ± 4.0%, P < 0.01) and absolute proximal reabsorption did not change, indicating impairment of proximal glomerulotubular balance (GTB). No similar changes in haemodynamic or transport parameters were observed in the contralateral, innervated kidney, although vascular resistance increased.

3. In 9 experiments following denervation of the left kidney, systemic low dose infusion (10 ng/min) of atrial natriuretic factor (ANF) resulted in a fall in mean arterial blood pressure from 116 ± 3 mmHg to 107 + 3 mmHg (P < 0.05). In the denervated kidney ANF increased urine flow rate and sodium excretion to rates above those established following denervation alone. However, in the right kidney, despite the increased filtered load (35%, P < 0.01), the natriuretic and diuretic responses to ANF were abolished.

4. In the denervated kidney, ANF further reduced the fractional reabsorption of lithium from 53.6 ± 2.3% to 45.6 ± 3.8% (P < 0.05). GFR increased by 32% (a total of 49% higher than during pretreatment) but absolute proximal reabsorption (APR) did not change. However, in the right, innervated kidney ANF infusion produced a 35% increase in GFR accompanied by a 53% rise in APR.

5. It is concluded that the natriuresis induced by unilateral denervation is due predominantly to impaired proximal GTB. The natriuretic action of ANF was associated with further impairment of proximal GTB, not dependent upon decreasing activity of renal sympathetic nerves, but was abolished when filtration fraction and renal sympathetic tone were elevated.
CHANGES IN HEPATIC CYTOSOLIC GLUTATHIONE S‐TRANSFERASE ENZYMES INDUCED BY CLOTRIMAZOLE TREATMENT IN RATS
Authors: González P. , Tuñón M. J. , Manrique V. , Garcia‐Pardo L. A. , González J.
Published: June 2007

1. The influence of the antifungal agent clotrimazole on cytosolic glutathione S‐transferase activities was studied in male Wistar rats.

2. Animals received clotrimazole by gastric lavage for 3 days (75 mg/kg per day). Hepatic glutathione S‐transferase activity was determined with five different substrates: 1‐chloro‐2,4‐dinitrobenzene (CDNB), 1,2‐dichloro‐4‐nitrobenzene (DCNB), p‐nitrobenzyl chloride (PNBC), ethacrynic acid (EA) and trans‐4‐phenyl‐3‐buten‐2‐one (TPBO).

3. The largest increases in glutathione S‐transferase activity were found with CDNB, DCNB and PNBC (+ 61%, + 50% and + 50%, respectively, when expressed per mg of cytosolic protein). Enzyme activity toward EA was induced to a lower extent (+ 33%). Changes in the formation of the conjugate of TPBO were relatively small (+22%).

4. These data indicate a differential induction of glutathione S‐transferase isoenzymes and suggest that clotrimazole is a phenobarbital‐type inducer of enzyme activity.
USE OF METHIONINE‐ENKEPHALIN SULFOXIDE AND LEUCINE‐ENKEPHALIN RADIO‐IMMUNOASSAYS FOR THE MEASUREMENT OF ENKEPHALINS IN THE RAT BRAIN
Authors: Tiong George K. L. , Olley Jean E.
Published: June 2007

1. A radio‐immunoassay (RIA) for methionine‐enkephalin sulfoxide was developed and was used to measure methionine‐enkephalin, after oxidation, in the rat brain.

2. The RIA was performed together with assays that use commercially available met‐and leu‐enkephalin antisera.

3. Evidence is presented here indicating that antisera raised against the native met‐enkephalin peptide underestimate met‐enkephalin content due to loss of immunoreactivity after oxidation of peptide.

4. These results show that a more accurate measurement of met‐enkephalin may be obtained by using the met‐enkephalin sulfoxide RIA. The cross‐reactivity of met‐enkephalin with the leu‐enkephalin RIA was diminished following oxidation of peptide.
μ‐ AND K‐OPIATE RECEPTOR AGONISTS REDUCE PLASMA NEUROHYPOPHYSIAL HORMONE CONCENTRATIONS IN WATER‐DEPRIVED AND NORMALLY HYDRATED RATS
Authors: Evans R. G. , Olley J. E. , Rice G. E. , Abrahams J. M.
Published: June 2007

1. The effects of μ‐ and K‐opiate receptor agonists on plasma concentrations of immunoreactive (ir) oxytocin (OXY) and arginine vasopressin (AVP) in normally hydrated and water‐deprived rats were studied.

2. Water‐deprivation for 36 h elevated both plasma ir‐OXY and ir‐AVP concentrations of Long‐Evans rats. These elevated levels were lowered in a dose‐dependent manner after subcutaneous administration of bremazocine (3–10 μg/kg), M320 (10–100 μg/kg) or morphine (0.1–10 mg/kg). Comparable reductions of plasma concentrations of ir‐AVP and ir‐OXY were observed.

3. Plasma concentrations of ir‐OXY and ir‐AVP of normally hydrated Long‐Evans rats were lower after subcutaneous administration of bremazocine (10 μg/kg), M320 (10 μg/kg) and morphine (1.0 mg/kg).

4. These data suggest that both μ‐ and K‐opiate receptor agonists inhibit both OXY and AVP release from the neurohypophysis of rats.
ENDOTHELIN IS BLOOD VESSEL SELECTIVE: STUDIES ON A VARIETY OF HUMAN AND DOG VESSELS IN VITRO AND ON REGIONAL BLOOD FLOW IN THE CONSCIOUS RABBIT
Authors: Cocks T. M. , Broughton A. , Dib M. , Sudhir K. , Angus J. A.
Published: June 2007

1. Endothelin (Et), a vasoconstrictor peptide, was 5–10‐fold more potent (lower EC50) on isolated ring segments of large veins than on large arteries removed from dog coronary, mesenteric, femoral, renal and internal mammary vasculature and from the human internal mammary pedicle.

2. In the dog large coronary artery, Et (10–30 nmol/L) caused transient relaxations partway through the generation of a concentration‐contraction curve. These relaxations were endothelium dependent.

3. In conscious rabbits treated with mecamylamine, Et (0.025–0.4 nmol/kg) caused a marked rise in renal vascular resistance but hindquarter vasodilation. Under the same conditions angiotensin II constricted both beds.

4. These studies suggest that Et is vascular bed and large vein selective in activity. It did not appear to be selective for large or small coronary arteries in vitro.