bluuebunny/crossref_metadata_2025 huggingface dataset:
OBSERVATIONS ON A NEW NON‐INVASIVE MONITOR OF SKIN BLOOD FLOW
Authors: Hales J. R. S. , Stephens F. R. N. , Fawcett A. A. , Daniel K. , Sheahan J. , Westerman R. A. , James S. B.
Published: June 2007

1. A ‘tissue perfusion monitor’ (TPM) to non‐invasively provide an index of skin blood flow (SkBF) has been developed; it employs photoelectric plethysmographic principles to measure changes in the nett flux of red blood cells in superficial microvasculature.

2. The ‘tissue perfusion index’ (TPI) varies in proportion to SkBF, provided local haemoglobin concentration does not change significantly. TPI of humans and experimental animals has been shown to indicate reliably, well established phenomena such as decreased SkBF in response to mechanical restriction, cold or Valsalva's manoeuvre, or increased SkBF in response to heat, acetylcholine, sodium nitrite or local nerve blockade.

3. SkBF in sheep was varied between 1 and 156 mL/100g per min as measured with radioactive microspheres. Simultaneous measurements were made using the TPM and four laser‐Doppler instruments. The TPI yielded a correlation coefficient of 0.938, and when data were expressed as percentage change, the regression line did not differ significantly from the line of identity and the root‐mean‐square‐error was 6.2%. Data for the laser‐Doppler indices of SkBF were, respectively, 0.549–0.786, highly significant deviations in slopes, and 13.6–16.7%.

4. Thus, the TPI is a reliable index of changes in SkBF. Compared with some other available instruments, the TPM is more precise; it is also less sensitive to movement artefact, can be completely portable by battery operation, probes can be multiplexed to a single meter and it is likely to be much less expensive than current lasers.

5. Applications include, for example, experimental investigations of SkBF in man and animals, clinical uses such as evaluation of the efficacy of regional nerve blockade or of circulatory restitution after reconstructive surgery, and clinical tests of neuro vascular function.
ONCOGENES: PAST, PRESENT AND FUTURE
Authors: Klinken S. Peter
Published: June 2007

1. Certain retroviruses contain specific genes (oncogenes) which induce tumours.

2. These viral genes were shown to have normal counterparts in the mammalian genome which were termed proto‐oncogenes or cellular oncogenes.

3. This breakthrough provided a molecular explanation for tumour formation; viz. cells become transformed when regulation of cellular oncogenes goes awry.

4. Evidence for aberrant control of proto‐oncogenes in human malignancies was obtained when chromosomal translocations in Burkitt's lymphomas and chronic myelogenous leukaemia localized to the myc and abl cellular oncogenes, respectively.

5. Recent studies have demonstrated that proto‐oncogenes govern cellular proliferation and can be from any part of the signal transduction pathway, for example, growth factors, receptors, intracellular second messengers or nuclear transcription regulators.
EFFECT OF MINERALOCORTICOIDS AND SALT LOADING ON RENIN RELEASE, RENAL RENIN CONTENT AND RENAL RENIN mRNA IN MICE
Authors: Barrett G. , Morgan T. , Smith M. , Aldred P.
Published: June 2007

1. DOCA and 9α‐fludrocortisone were given to mice on a high‐sodium diet for periods of up to 20 weeks, resulting in decreases in plasma renin concentration, renal renin concentration and renal renin mRNA with both treatments.

2. Plasma renin concentration was suppressed prior to suppression of renin mRNA and renal renin levels, indicating that suppression of synthesis and secretion of renin occur separately.

3. The decrease in renal renin concentration that occurred with DOCA was greater and more rapid than the decrease that occurred with 9α‐fludrocortisone, suggesting that DOCA caused intra‐renal breakdown of renin.

4. When DOCA was given to mice on a low‐sodium diet, plasma renin concentration and renal renin concentration increased, indicating that the effects of DOCA on renin levels were dependent on dietary sodium.

5. Renin secretion and synthesis appeared to be controlled by different mechanisms and sodium balance has an important effect on both processes.
PLASMA VASOPRESSIN AND ATRIAL NATRIURETIC FACTOR DURING HAEMORRHAGE: INFLUENCE OF CARDIAC AND AORTIC RECEPTORS
Authors: Courneya C. A. , Wilson N. , Ledsome J. R.
Published: June 2007

1. The changes in plasma concentrations of immunoreactive vasopressin (iVP) and atrial natriuretic factor (iANF) in response to haemorrhage (10–30% blood volume) were measured in 10 anaesthetized rabbits before and after cardiac receptor denervation (vagal nerve section). Carotid sinus pressure was maintained constant (60 mmHg) to eliminate any changing input from carotid baroreceptors.

2. Haemorrhage increased iVP before and after vagal nerve section indicating that withdrawal of input from aortic baroreceptors may have contributed to the increase in iVP.

3. Section of the vagus nerves attenuated the iVP response to haemorrhage.

4. There was no correlation between release of iVP and iANF.

5. Haemorrhage decreased iAF before and after vagal nerve section. Section of the vagus nerves increased iANF. Plasma iANF was highly correlated with atrial pressure and mean arterial pressure suggesting iANF release was secondary to changes in cardiac haemodynamics.
RAMIPRIL REDUCES ALBUMINURIA IN DIABETIC RATS FED A HIGH PROTEIN DIET
Authors: O'Brien R. C. , Cooper M. E. , Allen T. J. , Jerums G.
Published: June 2007

1. Streptozotocin diabetes was induced in Wistar‐Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n= 7), or no treatment (n= 7), and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks.

2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P < 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups.

3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P < 0.01).

4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.
RENAL VENOUS WEDGE PRESSURE IN RENAL WRAP HYPERTENSION IN RABBITS
Authors: Denton Kate M. , Anderson Warwick P.
Published: June 2007

1. Renal cellophane wrapping to produce hypertension causes thickening of the capsule of the kidney. To determine whether this compresses the kidney, deep renal vein wedge pressure was measured as an estimate of tissue pressure in anaesthetized rabbits 1 month after cellophane wrapping (n= 5) or a sham operation (n= 3).

2. Renal vein wedge pressure was 18.3 ± 2.0 mmHg in hypertensive rabbits and 8.4 ± 1.1 mmHg in the sham‐operated rabbits.

3. Arterial pressure was raised or lowered with angiotensin II or glyceryl trinitrate, respectively. Arterial and wedge pressures were approximately linearly related and, at any given arterial pressure, wedge pressure was approximately 8 mmHg higher in the cellophane‐wrapped kidney than in the kidney of the sham‐operated group.

4. These results, showing that renal wedge pressure is elevated in renal wrap rabbits, indicate that the kidneys are compressed, probably by the thickened renal capsule. This may explain the increased renal vascular resistance seen in this form of hypertension.
DIURETIC EFFECT INDUCED BY INTRARENAL INFUSION OF NISOLDIPINE IN ANAESTHETIZED DOGS
Authors: Kageyama M. , Matsumura Y. , Hayashi K. , Hosokawa T. , Morimoto S.
Published: June 2007

1. Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anaesthetized dogs.

2. Intrarenal arterial infusion of nisoldipine (10, 50 ng/kg per min) did not influence mean systemic blood pressure and renal haemodynamics, but did cause dose‐related increases in urine flow and urinary excretion of electrolytes. During nisoldipine infusion at the higher dose, the levels of fractional excretion of sodium, potassium and chloride were significantly elevated.

3. In the lithium clearance study, fractional lithium excretion, an index of fractional sodium excretion in the proximal tubules, was unchanged even with the higher dose of nisoldipine, whereas fractional sodium excretion in the distal tubules markedly increased.

4. Nisoldipine elicited a significant increment in osmolar clearance without altering the reabsorption of free water.

5. Thus, intrarenal administration of nisoldipine at a non‐hypotensive dose to anaesthetized dogs produced a significant diuretic effect without alteration in renal haemodynamics. Results in lithium clearance and free water clearance studies suggest that nisoldipine exerts a diuretic action by inhibiting sodium transport at the distal nephron segments beyond the proximal tubules.
BLOOD PRESSURE, PLASMA AND PITUITARY PROLACTIN RESPONSES TO BROMOCRIPTINE IN NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Tan B. K. H. , Hutchinson J. S.
Published: June 2007

1. The effects on blood pressure (BP), plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine (BRC) delivered by osmotic minipump were investigated in genetically hypertensive rats (GHR) and their normotensive (NT) controls.

2. In the GHR, the mean BP in the BRC‐treated group over the 13 day period of study was significantly lower than in the vehicle‐treated group. In the NT rats, the mean BP in the BRC‐treated group over the 13 day period was also significantly lower than in the vehicle‐treated group.

3. Mean plasma PRL concentration in the GHR and NT rats were comparable. In the GHR, the mean plasma PRL concentration taken on day 13 was significantly lower in the BRC‐treated group than in the vehicle‐treated group. In the NT rats, the mean plasma PRL concentration taken on day 13 in the BRC‐treated group was, however, not significantly different from that in the vehicle‐treated group.

4. The mean pituitary PRL content was not significantly different in the GH and NT rats. There was a greater suppression of pituitary PRL content in the BRC‐treated GHR than in the BRC‐treated NT rats compared with their respective vehicle‐treated groups.

5. The results raise the possibility that PRL may have an indirect role in the pathogenesis of the hypertension of the GHR.
CARDIOVASCULAR EFFECTS OF CENTRAL ADMINISTRATION OF β‐ENDORPHIN IN RATS RECEIVING NEONATAL INJECTION OF MONOSODIUM GLUTAMATE
Authors: Wong T. M. , Lee A. Y. S. , Chan R. K. W.
Published: June 2007

1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.e.) injection of β‐endorphin on arterial blood pressure (BP) in rats that received five intraperitoneal injections of monosodium glutamate (MSG) on alternate days in the first 10 days of life were studied.

2. β‐endorphin administered into the lateral ventricles caused a prolonged elevation in BP, whereas i.c. injection of the peptide resulted in an even longer lasting reduction in BP. In the MSG‐treated rat, the prolonged hypertensive effect of i.c.v. injection of β‐endorphin was completely abolished, but the effect of i.c. injection of the peptide was the same as that in the control. Since MSG treatment destroyed selectively the structures around the third ventricle, it is suggested that these structures, including the arcuate nucleus, may be responsible for mediating the cardiovascular effects of β‐endorphin.

3. The effects of central administration of β‐endorphin were completely blocked by naloxone, which mainly antagonizes the actions of μ‐receptor agonists and has no cardiovascular effects itself. The results suggest that μ‐receptors may be involved in mediation of the effects of β‐endorphin on the cardiovascular system and that β‐endorphin in the brain may not exert a tonic influence on the cardiovascular functions.
PERHEXILENE: EFFECTS ON HEPATIC LYSOSOMAL FUNCTION IN RATS
Authors: Sewell Richard B. , Horowitz John D. , Grinpukel Susan A. , Martin Glenn
Published: June 2007

1. Perhexilene, a long‐acting anti‐anginal drug, can induce adverse effects on the liver which may be dose‐dependent. At high concentrations, perhexilene causes marked morphological change in hepatocyte lysosomes. The current study examined the effect of ‘therapeutic’ doses of perhexilene on hepatic lysosomal function, particularly the biliary release of lysosomal enzymes, using an isolated perfused rat liver (IPRL) model.

2. Pharmacokinetic studies demonstrated that clearance of single doses of perhexilene by the perfused rat liver was dose‐dependent and established a ‘therapeutic’ dose of 0.6 mg using the IPRL. A 5 day pretreatment regimen of 20 mg/kg per day was shown to produce ‘therapeutic’ perhexilene concentrations of 150–210 ng/ml.

3. At perhexilene concentrations equating the ‘therapeutic’ range in man, the major effect of perhexilene was at the biliary pole of the hepatocyte. In 5 day pretreatment dose studies, lysosomal enzyme excretion into bile was markedly increased. In single dose studies, the increase in biliary lysosomal enzyme output partially reflected an increase in bile water production which was not seen with the 5 day pretreatment regimen. Hepatic and perfusate lysosomal enzyme activities were not affected.

4. This selective effect of perhexilene on hepatocyte‐to‐bile lysosomal excretion may reflect intracellular lysosomal drug localization.
COMPARISON OF THE PROPERTIES OF [3H]‐d‐2‐AMINO‐5‐PHOSPHONOPENTANOIC ACID AND [3H]‐dl‐2‐AMINO‐7‐PHOSPHONOHEPTANOIC ACID BINDING TO HOMOGENATES OF RAT CEREBRAL CORTEX
Authors: Manallack David T. , Sheehan Kerrie‐Anne M. , Beart Philip M.
Published: June 2007

1. The pharmacology and ionic regulation of [3H]‐2‐d‐2‐amino‐5‐phosphonopentanoic acid ([3H]‐d‐AP5) and [3H]‐dl‐2‐amino‐7‐phosphonoheptanoic acid ([3H]‐dl‐AP7) binding to homogenates of rat cerebral cortex were examined using radioligand binding methodology.

2. Both [3H]‐d‐AP5 and [3H]‐dl‐AP7 labelled a single population of binding sites with dissociation constants of 0.39 and 1.8 μmol/l, respectively. The density of binding sites found with [3H]‐dl‐AP7 was 13 times greater than that found with [3H]‐d‐AP5.

3. The ionic requirements of the [3H]‐d‐AP5 binding site in the presence of chloride were such that calcium acetate enhanced binding, while magnesium and sodium acetate both decreased binding. In the absence of chloride both calcium and chloride ions stimulated binding.

4. In a chloride‐free buffer calcium acetate stimulated binding of [3H]‐dl‐AP7 in a biphasic manner. Chloride ions (ammonium salt) enhanced binding slightly at low concentrations (0.1–1.0 mmol/l) above which binding was reduced to non‐specific levels. The ionic dependence of [3H]‐dl‐AP7 binding had some similarities to the previously defined GLU‐C site.

5. The pharmacological profile of the site labelled by [3H]‐d‐AP5 was consistent with that of a recognition site for N‐methyl‐d‐aspartate (NMDA) as defined in electrophysiological experiments. [3H]‐dl‐AP7 did not label an NMDA site as several non‐NMDA ligands displaced binding with high affinity and the binding was not stereospecific as found for [3H]‐d‐AP5. Moreover, the pharmacological profile of the [3H]‐dl‐AP7 site did not correspond to any excitatory amino acid receptor as presently defined.
EVIDENCE FOR A ROLE OF NITRIC OXIDE IN THE NEUROTRANSMITTER SYSTEM MEDIATING RELAXATION OF THE RAT ANOCOCCYGEUS MUSCLEC
Authors: Li C. G. , Rand M. J.
Published: June 2007

1. The nitric oxide (NO) synthesis inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA), but not d‐NMMA, inhibited the NANC‐mediated relaxations of the rat anococcygeus muscle, but did not affect the relaxation produced by sodium nitroprusside.

2. The inhibitory effect of l‐NMMA was reversed by l‐arginine but not by d‐arginine, and prior exposure to l‐arginine blocked the effect of l‐NMMA.

3. The noradrenergically mediated contractions of the anococcygeus elicited by field stimulation were slightly enhanced by l‐NMMA, but the response to noradrenaline was not affected.

4. The results suggest that NANC transmission in the rat anococcygeus muscle involves the generation of NO from arginine.
ANTICONVULSANT ACTIVITY OF DI‐N‐PROPYLACETATE AND BRAIN MONOAMINE METABOLISM IN THE RAT
Authors: Abed Wadie T.
Published: June 2007

1. Sodium di‐n‐propylacetate (DPA) treatment induced significant increases in brain contents of gamma‐aminobutyric acid (GABA), 5‐hydroxyindoleacetic acid (5‐HIAA) and homovanillic acid (HVA). Furthermore, the threshold for pentylenetetrazol (PTZ) clonic convulsions was also increased in response to DPA administration.

2. Pretreatment with inhibitors of monoamine synthesis α‐methyl‐p‐tyrosine (AMPT) and p‐chlorophenylalanine (PCPA) did not alter the anticonvulsant activity of DPA, but when given alone, both AMPT and PCPA caused significant decreases in brain monoamine contents and PTZ threshold seizures.

3. Experiments using probenecid suggest that the increases in 5‐HIAA and HVA seen after DPA treatment could have resulted from inhibition of their active transport out of the brain. These data indicate that the anticonvulsant action of DPA is not dependent on changes in monoamine metabolism in the brain.
PRELIMINARY STUDY ON THE ANTINOCICEPTIVE EFFECT OF ELEPHANT β‐ENDORPHIN
Authors: Wong Chak‐Lam , Wai Man‐Keung , Cheng Heung‐Chin , Chung David , Yamashiro Donald
Published: June 2007

1. Intraventricular administration of human β‐endorphin and elephant β‐endorphin significantly prolonged the tail flick response tested 30 min later. However, elephant β‐endorphin was about 7–8 times more potent than human β‐endorphin in the tail flick test.

2. β‐Endorphin1‐27 antagonized the antinociceptive effect of both human β‐endorphin and elephant β‐endorphin by the same extent. Naloxone also antagonized the antinociceptive effects of the β‐endorphins but it was less effective than β‐endorphin1‐27.

3. Human β‐endorphin and elephant β‐endorphin were of equal potency in inhibiting the abdominal constriction response induced by intraperitoneal (i.p.) acetic acid. Both β‐endorphin1‐27 and naloxone antagonized these effects of the β‐endorphins with naloxone being more effective.

4. The present study showed that different opioid receptor subtypes may be involved in the tail flick test and the abdominal constriction test. Furthermore, elephant β‐endorphin was a better antinociceptive agent than human β‐endorphin in the tail flick test.
VASODILATORY EFFECTS OF MILRINONE ON PULMONARY VASCULATURE IN DOGS WITH PULMONARY HYPERTENSION DUE TO PULMONARY EMBOLISM: A COMPARISON WITH THOSE OF DOPAMINE AND DOBUTAMINE
Authors: Tanaka Hiroyuki , Tajimi Kimitaka , Matsumoto Akinori , Kobayashi Kunio
Published: June 2007

1. The limited therapeutic role of pulmonary vasodilation reflects lack of their selectivity for the pulmonary vasculature, and many drugs have been evaluated for effectiveness; however, none has gained widespread clinical use.

2. Milrinone (MIL) is a newly synthetized phosphodiesterase inhibitor, which has potent positive inotropic and vasodilatory effects.

3. The present study shows the effects of MIL on the pulmonary circulation in dogs with pulmonary hypertension due to autologous muscle‐induced pulmonary embolism, and also demonstrates a comparison with those of dopamine and dobutamine.

4. As MIL showed potent vasodilatory effects on the pulmonary vasculature, it had a potential clinical role in the treatment of pulmonary hypertension.
EFFECT OF LIGNOCAINE ON CORONARY BLOOD FLOW, SYSTOLIC MYOCARDIAL FUNCTION AND MYOCARDIAL HIGH ENERGY PHOSPHATE STORES IN SWINE
Authors: Perlmutter Neal , Wilson Richard , Joyce Mary , Angello Debra , Gee David
Published: June 2007

1. To investigate the effect of lignocaine upon coronary blood flow, myocardial systolic wall function and high energy phosphate stores, lignocaine was administered as a rapid intravenous injection to 14 open chest anaesthetized swine.

2. Before and after injection, measurements were made of coronary blood flow by electromagnetic flow probe, per cent wall thickening by ultrasonic crystals, adenosine triphosphate (ATP) and creatine phosphate (CP) content by myocardial biopsy, and arterial pressure by central aortic catheter. The animals were divided into two groups based on whether or not they received a continuous low‐dose infusion of lignocaine prior to the study. Group I received the continuous low‐dose infusion of lignocaine and group II did not.

3. With a 2 mg/kg lignocaine injection, peak diastolic coronary flow rose significantly in groups I and II by 27±7 and 29±7% respectively. This was followed by a significant decline in per cent wall thickening in groups I and II of ‐11±2 and ‐19±6% respectively. In group I myocardial CP content decreased after lignocaine injection by 58±6% and ATP tended to rise even though systolic and diastolic pressure did not change significantly. In group II neither CP nor ATP changed significantly, but systolic and diastolic blood pressure decreased significantly.

4. Repeat lignocaine injections were given over a wider dosage range (0.5–4.0 mg/kg) to determine dose–response for lignocaine versus coronary blood flow. Coronary blood flow increased and per cent wall thickening decreased as doses of lignocaine were increased.

5. It was concluded that rapid intravenous lignocaine injection appeared to cause a dose‐dependent coronary dilatation and systolic dysfunction. Pre‐treatment with low‐dose continuous infusion of lignocaine appeared to result in a decrease in CP and a rise in ATP when compared with no pre‐treatment—despite a similar effect on myocardial function and coronary blood flow.
EFFECT OF LONG‐TERM ADMINISTRATION OF TESTOSTERONE OENANTHATE ON SYMPATHETIC NEUROTRANSMISSION TO RAT ISOLATED SEMINAL VESICLES
Authors: Chin Jaye P. F. , Pennefather Jocelyn N.
Published: June 2007

1. The effects of prolonged administration of testosterone oenanthate (TE) on sympathetic neurotransmission to the rat isolated seminal vesicle were examined.

2. TE was administered at either 1.2 or 2.4 mg/kg subcutaneously (s.c.) thrice weekly for 8 weeks. A separate group of rats was administered the vehicle, sesame oil, 0.5 mL/kg, s.c. at the same regime and used as controls. TE administration increased plasma testosterone and dihydrotestosterone levels and seminal vesicle weights. TE 2.4 mg/kg suppressed fertility in male rats.

3. The mean ‐log EC50 values of adrenalin and noradrenaline in seminal vesicles from the control group were 5.30 (95% confidence limits: 5.14, 5.58; d.f. = 14) and 4.92 (95% confidence limits: 4.56, 5.49; d.f. = 14) respectively. Neither of these estimates were modified by TE administration.

4. The mean noradrenaline content (μg/tissue) in seminal vesicles from control rats was 0.88±0.09 μg/tissue. This did not change with TE treatment. Tissue noradrenaline concentration (μg/g tissue), on the other hand, decreased by more than 50% in preparations from rats treated with TE. This was paralleled by a decrease in the density of catecholamine fluorescence.

5. Mean responses to field stimulation (20 pulses, 60 V dial setting, 2 ms, 1–70 Hz) appeared to decrease in preparations from TE treated groups; this decrease was, however, not statistically significant (P>0.05; d.f. = 15).

6. It is concluded that prolonged administration of testosterone oenanthate to rats, at doses sufficient to suppress fertility, decreases the density of sympathetic innervation to the seminal vesicle by increasing smooth muscle mass. Treatment does not, however, modify the responses of this preparation to exogenously added catecholamines.
RELATIONSHIP BETWEEN GASTRIC MUCOSAL PROSTAGLANDIN LEVELS AND HEALING OF GASTRIC LESIONS IN RATS
Authors: Kuroiwa Masaki , Sugiyama Satoru , Ohara Atsushi , Goto Hidemi , Tsukamoto Yoshihisa , Nakazawa Saburo , Ozawa Takayuki
Published: June 2007

1. This study was designed to determine whether or not endogenous prostaglandins (PG) contribute to the healing of gastric ulcers induced by high concentrations of ethanol or water immersion stress.

2. Ethanol‐induced gastric lesions; rats were divided into four groups: (1) the control group: untreated; (2) the indomethacin group: indomethacin (2 mg/kg) was injected intramuscularly (i.m.) once daily until the end of the experiment; (3) the ethanol group: rats were given 1 mL of 50% ethanol intragastrically; (4) the ethanol + indomethacin group: indomethacin (2 mg/kg) was injected (i.m.) once daily from 1 h after administration of 50% ethanol until the end of the experiment.

3. Water immersion stress‐induced gastric lesions; rats were divided into three groups: (1) control group: untreated; (2) stress group: rats were placed in a stress cage and immersed into a water bath (23°C) for 6 h; (3) stress + indomethacin group: indomethacin (2 mg/kg) was injected (i.m.) once daily for 3 consecutive days immediately after stress treatment or from 3 days after stress treatment until the end of the experiment.

4. Immediately after observation of the lesions, the fundic mucosal layer was separated from the muscle layer and mucosal PG levels were measured by high performance liquid chromatography in each group.

5. Indomethacin did not inhibit ulcer healing until 48 h after administration in the ethanol experiment, and until 3 days after administration in the water immersion experiment. In contrast, indomethacin inhibited ulcer healing thereafter in each experiment respectively.

6. Four kinds of PG, that is 6‐keto‐PGF1α PGF2α, PGE2 and PGD2 were detected in gastric mucosa. Indomethacin inhibited the recovery of PG levels, and significantly low PG levels were observed after indomethacin treatment.

7. It was noted from the effect of indomethacin that there are at least two phases of healing in gastric ulcers (i.e. the early phase and the late phase), and that PG might be linked with the late phase of ulcer healing.
EFFECT OF STRESS ON THE CATECHOLAMINE CONTENT OF THE ADRENAL GLAND OF INTACT AND BURSECTOMIZED CHICKS
Authors: Mahata Sushil K. , De Monisha , Pal Dhananjay , Ghosh Asok
Published: June 2007

1. Bursa‐intact and bursectomized chicks were exposed to cold–wet immobilization (CWI) stress for 1.5 min. The catecholamines (CA) from the adrenal gland were measured spectrofluorometrically 5, 15, 30 and 60 min after stress.

2. In bursa‐intact chicks, the CWI stress caused decrease of both norepinephrine and epinephrine from the adrenal glands 5 min after stress. Resynthesis of epinephrine exceeded the control value 30 and 60 min after stress.

3. In bursectomized chicks, the CWI stress brought about a decrease of norepinephrine 15 and 30 min and of epinephrine 30 and 60 min after stress.

4. The findings suggest that bursa facilitates early (5 min) release of CA and also helps in quick resynthesis of epinephrine during stress.
MEASUREMENT OF BLOOD‐BRAIN BARRIER PERMEABILITY
Authors: Robinson P. J.
Published: June 2007

1. Experimental determinations of blood‐brain barrier permeability from measurements of uptake of tracers by brain are limited in two ways. First, there are experimental limitations that are specific to the particular method being used. These limitations include the range of permeability values that a particular method can reliably determine (sensitivity); whether repeated experiments are possible in the same animal; whether regional values can be determined; and to what degree the chemical composition of the perfusate passing through the brain can be controlled.

2. A second set of limitations on permeability determinations is of a more general, physiological nature. These constraints apply to a greater or lesser degree to all experimental determinations, and may limit the accuracy and reliability of the permeability values obtained; although certain reliable upper and lower bounds can be determined. These general factors include: capillary heterogeneity (i.e. variations in capillary lengths, surface areas, blood flows, etc.); the possibility of binding to circulating plasma proteins, especially albumin; and the possibility of capillary recruitment and de‐recruitment with changes in cerebral blood flow.
EFFECT OF ACETYLCHOLINE AND MORPHINE ON BRONCHIAL SMOOTH MUSCLE CONTRACTION AND ITS MODULATION BY STEROID HORMONES
Authors: Nabishah B. M. , Morat P. B. , Khalid B. A. K. , Kadir B. A.
Published: June 2007

1. The effects of corticosteroid pretreatment on acetylcholine (ACH)‐induced contraction of bronchial smooth muscle (BSM) were studied.

2. ACH dose‐response curves for dexamethasone (DM)‐ and corticosterone (B)‐treated but not deoxycorticosterone (DOC)‐treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH.

3. Morphine enhanced BSM contraction in response to ACH by 20%. DM suppressed this enhancement.

4. These findings correlated well with the reduction of muscarinic receptor numbers in BSM by glucocorticoids in our previous study. In addition, glucocorticoids reduced the sensitivity of BSM to opioids.
COMPARISON OF THEOPHYLLINE AND ENPROFYLLINE EFFECTS ON HUMAN NEUTROPHIL SUPEROXIDE PRODUCTION
Authors: Kaneko Michie , Suzuki Kenji , Furui Hidehiko , Takagi Kenzo , Satake Tatsuo
Published: June 2007

1. We investigated effects of theophylline (widely used for the treatment of asthma) and enprofylline (a new xanthine derivative with negligible adenosine antagonism) on O2‐ production by human neutrophils with n‐formyl‐methionylleucyl‐phenylalanine (FMLP) stimulation.

2. Therapeutic concentrations of theophylline (1–100 μmol/L) enhanced O2‐ production, maximally by 43.1 ± 24.4% at 30 μmol/L; the same concentrations of enprofylline inhibited O2‐ production.

3. When each agent was administered after pre‐incubation with adenosine deaminase (ADA) (0.1 U/mL), O2‐ production was inhibited in a concentration‐dependent manner in comparison with that under administration of ADA alone.

4. These results suggest that the difference of effects in the two xanthine derivatives at therapeutic concentrations might be due to the presence or absence of adenosine antagonism.
EFFECTS OF STROPHANTHIDIN ON THE SLOW INWARD CURRENT IN GUINEA‐PIG ISOLATED VENTRICULAR MYOCYTES
Authors: Yang Lie , Vassalle Mario
Published: June 2007

1. The effect of strophanthidin on the slow inward current (Isi) and on contractile force were studied in guinea‐pig isolated ventricular myocytes and intact papillary muscles, respectively. In myocytes, both low (10 nmol/L) and high (1–10 μmol/L) concentrations had small or no effects in either direction on Isi whereas norepinephrine (10–100 nmol/L) increased it. To determine whether the same results are obtained after decreasing or increasing intracellular calcium or sodium, the same concentrations of strophanthidin were tested in different procedures that are known to (i) increase [Ca]i and decrease [Na]i (high [Ca]o, 3.6–5.4 mmol/L; low [Na]o, 112 mmol/L; (ii) decrease [Ca]i and increase [Na]i (low [Ca]o, 0.45–1 mmol/L; Sr, 1 mmol/L; (iii) decrease [Ca]i and [Na]i (Cd, 0.1–0.2 mmol/L); and (iv) increase [Ca]i and [Na]i (veratridine, 0.2 μmol/L). High [Ca]o and veratridine increased whereas low [Ca]o and Cd decreased Isi. In contrast, during these various procedures, strophanthidin had small and inconsistent effects at a low or high concentration. In intact papillary muscles, low strophanthidin decreased whereas high strophanthidin increased contractile force. It is concluded that strophanthidin has little direct or indirect effect on Isi and that the decrease in force by low and increase in force by high concentrations in intact muscle are probably related to demonstrated decrease and increase, respectively, in intracellular sodium activity.
A RENIN‐SECRETING TUMOUR SENSITIVE TO CHANGES IN CENTRAL BLOOD VOLUME (PRESUMABLY VIA SYMPATHETICS) BUT NOT TO CIRCULATING ANGIOTENSIN II
Authors: Gordon Richard D. , Tunny Terry J. , Klemm Shelley A. , Finn Wendy L. , Hawkins Peter J. , Hunyor Stephen J. , Norris John J.
Published: June 2007

1. A 17 year old female presented with severe hypertension, hypokalaemia and elevated levels of plasma renin activity due to a renin‐secreting tumour.

2. Renin was responsive to posture, low sodium diet, saline infusion and frusemide, but relatively unresponsive to raising or lowering circulating levels of angiotensin II.

3. Renal venous renin levels lateralized to the side of the tumour with good contralateral suppression when measured with control of posture and avoidance of prior stimulation, with and without angiotensin converting enzyme inhibition.

4. Levels of atrial natriuretic peptide were elevated and responsive to posture, saline infusion and angiotensin infusion.

5. The tumour was evident on computerized tomography, but not on intravenous pyelography or renal angiography.

6. Responsiveness of renin secretion to normal stimuli in reninoma may make diagnosis difficult, and renal vein sampling under controlled conditions is necessary.
A FACTORIAL STUDY OF FAT AND FIBRE CHANGES AND SODIUM RESTRICTION ON BLOOD PRESSURE OF HUMAN HYPERTENSIVE SUBJECTS
Authors: Sciarrone S. E. G. , Rouse I. L. , Rogers P. , Beilin L. J.
Published: June 2007

1. Diets used to reduce sodium intake often involve changes in fats and fibre which might themselves affect blood pressure and/or lipid metabolism. To evaluate the relative importance of these dietary changes for the management of hypertension we have studied the independent and additive effects of sodium restriction (60 mmol/day) and a low fat (30% energy), high P/S ratio (1.0), high fibre (30–50 g/day) ‘cholesterol lowering’ diet.

2. Ninety‐five hypertensives entered a four group parallel study with a factorial design. Following 5 weeks familiarization subjects [BP range 109/66–168/105 mmHg] were randomly assigned to either a ‘low sodium, cholesterol lowering’ diet or a ‘low sodium, cholesterol maintaining’ diet. Half the subjects in each group were then assigned to 100 mmol/day NaCl supplement and the remainder to placebo. These diets were continued for 8 weeks. Seventy‐nine of the 91 hypertensives who completed the study were on antihypertensive therapy throughout.

3. Mean urinary sodium excretion decreased from 137 (54 mmol/day (n= 43) at baseline (B) to 52 (32) mmol/day (n= 45, P= 0.0001) during intervention (I) in the low sodium groups and remained unchanged in the groups which received slow sodium (B = 129 [46], n= 43; I = 134 [29], n= 42). Diet record and plasma fatty acid analysis confirmed that the dietary aims of the study were achieved.

4. Sodium restriction reduced supine and standing systolic BP by a mean (± s.e.m.) of 6±2 and 6±4 mmHg, respectively (P<0.005). The low fat/high fibre diet had no independent or additive effect on blood pressure reduction but reduced total and LDL cholesterol by an average of 0.74 and 0.59 mmol/L, respectively (P<0.0001).

5. In terms of reducing overall risk of cardiovascular disease, diets which combine sodium restriction with measures to reduce LDL cholesterol would appear optimal.
ISOLATED SYSTOLIC HYPERTENSION: DOES IT REALLY EXIST ON AMBULATORY BLOOD PRESSURE MONITORING?
Authors: Silagy C. A. , McNeil J. J. , McGrath B. P.
Published: June 2007

1. The diagnosis of isolated systolic hypertension, diastolic hypertension and normotension in elderly subjects, as defined by casual office blood pressure measurement, was compared with 24 h ambulatory blood pressure monitoring using an Accutracker II.

2. Mean day‐time ambulatory blood pressure monitoring underestimated the casual systolic blood pressure in all three clinical groups. Diastolic pressure was not underestimated to the same extent.

3. Ambulatory blood pressure monitoring best reflected casual blood pressure determination for normotensive subjects. In subjects with isolated systolic hypertension ambulatory blood pressures were only consistent with that diagnosis for 8% of the day time period. For 34% of the day time, their ambulatory blood pressures were consistent with diastolic/ mixed hypertension.

4. It is concluded that isolated systolic hypertension may not be a sustained condition, but rather an isolated response to office measurement of blood pressure.
PREVALENCE OF LEFT VENTRICULAR HYPERTROPHY IN ELDERLY PATIENTS WITH WELL CONTROLLED HYPERTENSION
Authors: Jones Elizabeth , Morgan Trefor O. , Califiore Paul , Johns Jennifer
Published: June 2007

1. Left ventricular hypertrophy (LVH) was measured by echocardiography in 154 patients, mostly males, aged 55 years or more, with hypertension who had been well controlled for at least 2 years.

2. Satisfactory studies with no other cardiac lesions were available for 103 patients; 52% had LVH and 48% had normal left ventricular dimensions.

3. In patients with well controlled hypertension there was a high prevalence of LVH despite adequate control for at least 2 years. Neither the level of control nor the drugs used appeared to predict the outcome.

4. Consideration needs to be given to earlier treatment, greater lowering of blood pressure, or different drugs to reduce this high prevalence of LVH.
EFFECTS OF REGULAR ALCOHOL CONSUMPTION ON 24 HOUR AMBULATORY BLOOD PRESSURE RECORDINGS
Authors: Howes L. G. , Krum H. , Phillips P. A.
Published: June 2007

1. Regular consumption of 1 g/kg of alcohol for 4 days did not significantly alter mean 24 h blood pressures compared with a similar period when dextrose was consumed to match caloric intake.

2. In contrast, the variability of diastolic blood pressure was increased by regular alcohol consumption.

3. Increased blood pressure variability in response to the stress of blood pressure measurement may contribute to the observed association between hypertension and alcohol consumption.
EFFECT OF GRADED ADRENALINE INFUSION ON ARTERIAL ADRENALINE CLEARANCE IN NORMOTENSIVE AND HYPERTENSIVE MAN
Authors: Bachmann Anthony W. , Gordon Richard D. , Bathgate Ross A.D. , Thompson Robyn E.
Published: June 2007

sUMMARY

1. Arterial adrenaline (ADR) levels were measured during graded ADR infusions in normotensives (NT) and in mild hypertensives (HT), in order to test the hypothesis that ADR enhances its own clearance in NT.

2. Although infusion of ADR resulted in similar arterial ADR levels in NT and HT, increases in systolic blood pressure (SBP) and heart rate (HR) and decreases in diastolic blood pressure (DBP) were greater during ADR infusion in HT than in NT.

3. Twenty minutes after cessation of infusion, SBP and HR remained elevated in HT but not in NT.

4. No evidence was found supporting enhanced ADR clearance during increasing ADR levels in NT or HT.
INHIBITION OF ENDOTHELIAL NITRIC OXIDE BIOSYNTHESIS BY N‐NITRO‐l‐ARGININE
Authors: Dubbin Philip N. , Zambetis Maria , Dusting Gregory J.
Published: June 2007

1. The actions of N‐nitro‐L‐arginine (NOLA) on the release of nitric oxide (NO) from arterial endothelial cells was studied in rat isolated thoracic aortic rings and by bioassay of NO derived from cultured bovine aortic endothelial cells.

2. NOLA (3–10 μmol/L) caused concentration‐dependent inhibition of acetyl‐choline‐induced relaxation of phenylephrine‐contracted rat aortic rings, which is dependent on the release of NO from the endothelium. The inhibitory actions of NOLA could be prevented by pre‐ and co‐incubation with L‐arginine (1 mmol/L).

3. Endothelium‐independent relaxation induced by sodium nitroprusside was not affected by NOLA.

4. The release of NO from bovine aortic endothelial cells, induced by bradykinin (10 nmol/L), was detected by bioassay on pre‐contracted rabbit aortic strips. NOLA (1–3 μmol/L, given through the cell column) reduced or abolished the release of NO, but did not affect relaxations of the bioassay tissues induced by glyceryl trinitrate or authentic NO.

5. These data indicate that NOLA potently inhibits the biosynthesis of NO from L‐arginine, and thus prevents its release from arterial endothelial cells. It may be a useful pharmacological tool for probing the significance of NO biosynthesis in cardiovascular function.
SODIUM‐DEPENDENT, ETHYLISOPROPYLAMILORIDE‐SENSITIVE MECHANISMS REGULATE INTRACELLULAR pH IN HUMAN VASCULAR SMOOTH MUSCLE
Authors: Bobik Alex , Neylon Craig B. , Little Peter J. , Jr Edward J. Cragoe , Weissberg Peter L.
Published: June 2007

1. The pH‐sensitive dye 2,7‐biscarboxy‐ethyl‐5(6)‐carboxyfluorescein (BCECF) was used to examine the contribution of Na+‐H+ exchange and bicarbonate‐dependent processes to intracellular pH (pHi) regulation in cultured human vascular smooth muscle.

2. The recovery of pHi following an NH4Cl‐induced acidosis was Na+‐dependent and could be inhibited by ethylisopropylamiloride (200 μmol/L). Recovery was unaffected by the anion exchange inhibitor 4‐acetamido‐4′‐isothio‐cyano‐stilbene‐2,2′‐disulfonic acid (200 μmol/L).

3. Recovery from intracellular acidosis was more rapid when bicarbonate ions were present in the extracellular medium.

4. The results suggest that Na+‐H+ exchange as well as an Na+‐dependent bicarbonate process, which can be inhibited by ethylisopropylamiloride, can influence the ability of smooth muscle to recover from intracellular acidosis.
SHIFT IN THE BAROREFLEX‐RENAL NORADRENALINE SPILLOVER CURVE DURING THE DEVELOPMENT OF CONGESTIVE HEART FAILURE IN THE RABBIT
Authors: McGrath Barry P. , Sano Naoki , Way Diana
Published: June 2007

1. Changes in renal sympathetic nerve activity (RSNA) were investigated during the development of congestive heart failure (CHF) in rabbits with doxorubicin‐induced cardiomyopathy.

2. Controls (saline treated, n= 5) and doxorubicin‐treated rabbits (1 mg/kg administered intravenously twice weekly, n= 5) were studied after 4 and 6 weeks treatment.

3. RSNA was estimated by measuring renal noradrenaline spillover rate under resting conditions and in response to changes in arterial pressure induced by phenylephrine and sodium nitroprusside infusions.

4. In the doxorubicin‐treated group, resting renal noradrenaline spillover was increased at 4 weeks (24.2 ng/min, s.e.m. = 2.5, n= 5) compared with controls (15.2 ng/min, s.e.m. = 2.4, n= 5; P<0.01) and remained elevated.

5. The baroreceptor–renal noradrenaline spillover curve showed a significant upward shift in the doxorubicin‐treated group at 4 weeks. After 6 weeks both heart rate and renal noradrenaline spillover responses to hypotension were significantly blunted.

6. It is suggested that increased RSNA occurs early during the development of CHF in doxorubicin‐treated rabbits. The observed changes in the baroreflex responses suggest that different mechanisms may contribute to this increased RSNA at different stages of CHF.
EFFECTS ON SHEEP BLOOD PRESSURE OF TREATMENT WITH ANGIOTENSIN, STEROIDS AND SALT
Authors: Lumbers Eugenie R.
Published: June 2007

1. Angiotensin II (AII, 0.22 μg/min) infused for 7–14 days, into adult unanaesthetized wethers, caused a rise in blood pressure of 7±3/7±3 mmHg (mean ± s.e.m.) from control values of 90±5/54±3 mmHg (P<0.05, n= 11). Cardiac output and pulse interval were not affected. A high salt intake had no effect on blood pressure, cardiac output and pulse interval, nor did it potentiate the action of AII.

2. Ethinyl oestradiol (EE, 20 mg/week) caused a small fall in systolic and diastolic pressure of 6±3/6±5 mmHg (n= 7, P<0.1, P<0.05). When AII (0.22 μg/min) was given with EE, it still caused a significant rise in blood pressure (P<0.01). The synthetic progestin (1 mg of norethisterone [NE] for 8–18 days) plus a high salt diet had no effect on arterial pressure and cardiac output but pulse interval rose significantly (P<0.05).

3. Therefore the reduction in vascular reactivity to angiotensin seen in human pregnancy is probably not related to high levels of oestrogen. Further, NE combined with a high salt diet does not cause hypertension in sheep.
METABOLISM OF TETRADECAPEPTIDE, ANGIOTENSINOGEN AND ANGIOTENSIN I AND II BY ISOLATED PERFUSED RAT HINDLIMBS
Authors: Campbell Duncan J. , Ziogas James , Kladis Athena
Published: June 2007

1. We investigated the mechanism of tetradecapeptide‐induced vasoconstriction by studying the metabolism of tetradecapeptide (TDP), angiotensinogen, and angiotensin I (AI) and angiotensin II (AII) by isolated perfused rat hindlimbs.

2. Using HPLC and specific RIAs we have quantified six angiotensin peptides: pentapeptide(4–8), hexapeptide(3–8), heptapeptide(2–8), octapeptide(1–8), nonapeptide(2–10) and decapeptide(1–10) in hindlimb effluent.

3. TDP‐induced vasoconstriction was associated with generation of predominantly AI and AII, with smaller amounts of the other peptides measured.

4. Captopril prevented vasoconstriction and inhibited AII production by 80%, indicating a dominant role for AI generation in the vascular response to TDP.

5. Evidence that renin is not the enzyme responsible for AI generation from TDP includes: first, the failure of angiotensinogen to cause vasoconstriction or angiotensin peptide generation despite very high amounts of AI and AII generation from TDP; second, the resistance of the TDP‐induced vasoconstriction and angiotensin peptide generation to inhibition by pepstatin; and third, the failure of bilateral nephrectomy 24 h before the experiment to influence the vascular and angiotensin peptide response to TDP.

6. AII was cleared with 41% efficiency, with generation of penta‐, hexa‐, and heptapeptides.

7. AI was cleared with 59% efficiency; this was reduced to 24% by captopril, indicating a conversion of at least 35% of AI to AII by ACE.

8. These studies have identified vascular metabolism of AI and AII to be an efficient process, with both ACE and aminopeptidases playing an important role, and indicate that those peptidases which cleave TDP to generate AI are unlikely to play any role in AI generation in vivo.
INFLUENCE OF NEONATAL HYPOTHYROIDISM ON ADRENAL TYROSINE HYDROXYLASE ACTIVATION IN THE YOUNG RAT
Authors: Valens M. , Gripois D.
Published: June 2007

1. Adrenal TH activation was elicited in young rats (aged 4,6 and 14 days) by insulin hypoglycaemia. In the control rats, TH activation varied between 125 and 147% above basal values.

2. Neonatal hypothyroidism induced by PTU treatment impaired TH activation. Compensatory treatment with T3 to the PTU‐treated young rats led to a return to control activation.
ANTIDIURETIC EFFECTS OF NEUROTENSIN IN CHLORALOSE ANAESTHETIZED DOGS
Authors: Kivlighn Salah D. , Jandhyala Bhagavan S.
Published: June 2007

1. Effects of cerebroventricular and/or intravenous infusions of neurotensin (NT), an endogenous tridecapeptide, on haemodynamics and renal function were investigated in chloralose anaesthetized dogs.

2. Cerebroventricular infusions (i.c.v.) of NT (10‐6 mol/L and 10‐5 mol/L, 0.1 mL/min) for 30 min did not produce any significant alterations in the measured variables. In the vagotomized dogs, intravenous (i.v.) infusion of NT (10‐5 mol/L) at a rate of 0.1 mL/min for 30 min significantly lowered the arterial blood pressure and glomerular filtration rate; these effects were accompanied by pronounced reductions in the urine flow and urinary sodium excretion and marked increases in urine osmolality.

3. In the dogs with vagi intact, i.v. infusions of NT failed to produce any alterations in the blood pressure; however, renal effects of NT were essentially identical to those observed in the vagotomized dogs.

4. Infusions of NT (10‐6 mol/L) and/or NT‐metabolites NT1‐8 and NT8‐13 (10‐5 mol/L) directly into the renal artery failed to produce any significant alterations in the urine flow. Antidiuretic effects of i.v. NT were not prevented by acute renal denervation, adrenalectomy, or pretreatment of the animals with naloxone. However, morphine pretreatment completely abolished the hypotensive and antidiuretic effects of NT.

5. It is proposed that i.v. infusion of NT rapidly facilitates the secretion of an endogenous substance possessing potent antidiuretic properties and opiate mechanisms are involved in mediating such an effect. Although it appears unlikely, a role for vasopressin cannot be ruled out.