bluuebunny/crossref_metadata_2025 huggingface dataset:
METHODOLOGICAL EVALUATION OF INDIRECT CALORIMETRY DATA IN LEAN AND OBESE RATS
Authors: Rafecas Immaculada , Esteve Montserrat , Fernández‐López José‐Antonio , Remesar Xavier , Alemany Marià
Published: June 2007

1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60‐day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry.

2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters.

3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry.

4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance.

5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry or direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one‐fifth of total energy produced in the three rat stocks.

6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/ degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked pattern.

7. The results obtained indicate that lean and obese rats can be studied using the same indirect calorimetry formulae provided that there is an adequate measure of protein oxidation and the composition of diet does not differ.
THE ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR, PERINDOPRIL, PREVENTS CARDIAC HYPERTROPHY IN LOW‐RENIN HYPERTENSIVE RATS
Authors: Nakamura Fumiaki , Nagano Masahiro , Higaki Jitsuo , Higashimori Koichi , Morishita Ryuichi , Mikami Hiroshi , Ogihara Toshio
Published: June 2007

1. To examine whether an angiotensin‐converting enzyme (ACE) inhibitor prevents left ventricular (LV) hypertrophy even in low‐renin hypertension, we studied the effect of the administration of perindopril on cardiac hypertrophy induced by partial renal ablation in hypertensive rats.

2. Rats that had undergone partial nephrectomy were randomly divided into four groups that received the following as drinking water: Group A, tap water; Group B, 1% sodium chloride (NaCl); Group C, NaCl + perindopril 3 mg/ kg per day; and Group D, NaCl + perindopril 1 mg/ kg per day. Plasma renin activity (PRA), angiotensin‐II (AII) concentration and cardiac tissue AII were measured.

3. Supplementation of NaCl following nephrectomy increased the blood pressure and cardiac weight compared with rats that had undergone nephrectomy alone (P<0.05). Treatment with perindopril (3 mg/kg per day) did not affect the blood pressure and plasma AII but inhibited the increase of cardiac weight (P<0.05). Left ventricular AII was decreased in cases of reduced renal mass hypertension, but was not changed by treatment with perindopril.

4. These results demonstrate that perindopril may be able to prevent LV hypertrophy even in low‐renin hypertension, which was not mediated by a reduction of blood pressure or suppression of the circulating and cardiac renin‐angiotensin systems. Other mechanisms of ACE inhibitors may contribute to the cardioprotective effects.
THE INHIBITION OF NITRIC OXIDE‐MEDIATED RELAXATIONS IN RAT AORTA AND ANOCOCCYGEUS MUSCLE BY DIPHENYLENE IODONIUM
Authors: Rand M. J. , Li C. G.
Published: June 2007

1. The effects of diphenylene iodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate‐dependent oxidases (which generate superoxide anions), were studied on nitric oxide (NO)‐mediated responses in isolated preparations of the rat aorta and anococcygeus muscle.

2. In aortic rings, the endothelium‐dependent relaxant action of acetylcholine was reduced by DPI (0.3–10 μmol/L) in a concentration‐dependent manner and abolished by the NO synthase (NOS) inhibitor L‐nitro‐NG‐arginine methylester (l‐NAME; 100 μmol/L). Relaxations induced by sodium nitroprusside (SNP) or NO were not affected by DPI or l‐NAME.

3. In anococcygeus muscles, DPI (0.3–10 μmol/ L) as well as l‐NAME (5–100 μmol/L) produced concentration‐dependent reductions of relaxations produced by nitrergic nerve stimulation. Relaxations induced by NO and SNP were not affected by either DPI or l‐NAME. l‐Arginine (1 mmol/L) prevented the reduction of nitrergic relaxations by l‐NAME but not by DPI.

4. Contractions of anococcygeus muscles elicited by exogenous noradrenaline (1 μmol/ L) were not affected or were inhibited by DPI (0.3–10 μmol/L), but the contractions elicited by noradrenergic nerve stimulation were significantly enhanced by DPI and l‐NAME. When noradrenergic contractions had already been maximally enhanced by l‐NAME (100 μmol/L), DPI produced no further enhancement. l‐Arginine (1 mmol/L) prevented the enhancement of noradrenergic contractions by l‐NAME but not by DPI.

5. The efflux of radioactivity induced by field stimulation from anococcygeus muscles previously incubated with [3H]‐noradrenaline was not affected by either DPI or l‐NAME.

6. Superoxide dismutase (SOD, 100 U/mL) had no significant effects on noradrenergic contractions, nitrergic relaxations, relaxations induced by NO or the actions of DPI in the rat anococcygeus muscle.

7. The results suggest that the effects of DPI in reducing the NO‐mediated relaxations produced by acetylcholine in rat aortic rings and stimulation of nitrergic nerves in the rat anococcygeus muscle are due to the inhibition of NOS in these tissues. The effects of DPI were not sensitive to l‐arginine, and thus the mechanism of inhibition of NOS differs from that of l‐NAME.
CIRCADIAN VARIATIONS OF BLOOD PRESSURE AND PULSE RATE IN ESSENTIAL HYPERTENSIVES WITH DIABETES MELLITUS
Authors: Matsumura Kiyoshi , Abe Isao , Tsuchihashi Takuya , Kobayashi Kazuo , Fujishima Masatoshi
Published: June 2007

1. The circadian variations of blood pressure and pulse rate in essential hypertensives either with or without diabetes mellitus were studied.

2. Diabetic patients with orthostatic hypotension showed an increase in variability of blood pressure and a decrease in that of pulse rate when assessed by coefficient of variation. Cosinor analysis showed no significant circadian rhythm in both blood pressure and pulse rate in these patients.

3. There were no differences in the circadian variations of blood pressure and pulse rate between essential hypertensives with and without diabetes mellitus unless orthostatic hypotension was present.

4. These results suggest that diabetes mellitus per se does not have any effects on the circadian variations of blood pressure and pulse rate in essential hypertensives unless autonomic neuropathy is present.
NEUROLEPTICS INDUCE PENILE ERECTION IN THE RABBIT
Authors: Naganuma H. , Egashira T. , Fujii I.
Published: June 2007

1. Intramuscular (i.m.) administration of the neuroleptics chlorpromazine, haloperidol and spiperone at doses ranging from 0.1 to 0.4 mg/kg in male rabbits induced a dose‐dependent penile erection.

2. The i.m. administration of the α1‐adrenoceptor antagonists prazosin and bunazosin (0.1–0.4 mg/kg), induced a dose‐dependent penile erection. However, that of the peripheral dopamine receptor antagonist domperidone (0.4–4.0 mg/kg) and the dopamine receptor agonist apomorphine (0.1–1.0 mg/kg) did not. Penile erection was not induced by i.m. injection of chlorpromazine in combination with intrapenile administration of the α1‐adrenoceptor agonist methoxamine.

3. Penile erection was induced by the administration of chlorpromazine (0.25–1.00 mg/body) into the lateral cerebral ventricle. At a low dose, however, the administration of chlorpromazine into the lateral ventricle induced a less notable penile erection than that induced intramuscularly.

4. Penile erection was induced by i.m. injection of the ganglionic blocker hexamethonium (5–20 mg/ kg). When chlorpromazine was given after pretreatment with hexamethonium, penile erection was more notable than that induced by either drug given alone.

5. These results suggest that neuroleptics could act locally in the penile structure to cause penile erection by α1‐adrenoceptor‐blocking actions.
BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION
Authors: Panozzo Maria P. , Fabris Carlo , Basso Daniela , Favero Giuseppe Del , Infantino Aldo , Cecchetto Attilio , Plebani Mario , Naccarato Remo
Published: June 2007

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho‐jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague‐Dawley rats divided into four groups.

2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho‐jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham‐operated rats). Serum and bile samples were then serially collected for 2 h.

3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham‐operated rats.

4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E.

5. In conclusion, bile duct obstruction greatly affects the plasma‐bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho‐jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.
A STUDY ON THE ROLE OF CHOLINERGIC AND GAMMA AMINO BUTYRIC ACID SYSTEMS IN THE ANTI‐NOCICEPTIVE EFFECT OF GOSSYPIN
Authors: Viswanathan S. , Thirugnanasambantham P. , Ramaswamy S. , Bapna J. S.
Published: June 2007

1. The participation of cholinergic and gamma amino butyric acid (GABA) neurotransmitter systems in the anti‐nociceptive effect of gossypin was investigated using pharmacological tools.

2. Physostigmine potentiated its anti‐nociceptive response while atropine failed to modify it significantly.

3. THIP (4,5,6,7‐tetra hydroisoxazolo (5,4‐C) pyridin‐3‐ol) and gossypin treatment produced an additive response while bicuculline attenuated the anti‐nociceptive response of gossypin. Similar observations were recorded for morphine.

4. It is suggested that cholinergic and GABAergic systems play a role in gossypin‐induced anti‐nociception.
INVESTIGATION OF CLASS I ANTI‐ARRHYTHMIC DRUG ACTIONS ON GUINEA‐PIG CARDIAC MITOCHONDRIAL LACTATE DEHYDROGENASE ACTIVITY
Authors: Dzimiri Nduna , Almotrefi Abdulrahman A.
Published: June 2007

1. The effects of the Class I anti‐arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea‐pig heart preparations.

2. All the tested drugs inhibited the enzyme activity in a concentration‐dependent fashion, exhibiting varying profiles in their actions. Lidocaine exhibited inhibitory concentration 20% (IC20) and IC50 values of 0.52 ± 0.02 mmol/L and 25.6 ± 0.5 mmol/ L, procainamide 6.0 ± 0.2 mmol/ L and 108 ± 7.2 mmol/L, phenytoin 3.4 ± 0.06 μmol/L and 0.34 ± 0.02 mmol/L, quinidine 39.2 ± 1.2 μmol/L and 9.8 ± 0.8 mmol/L and tocainide 2.7 ± 0.3 mmol/L and 44.6 ± 2.5 mmol/L.

3. According to the IC50 values, this is the order of their inhibitory potencies: phenytoin > quinidine > lidocaine > tocainide > procainamide. This trend is in general agreement with the lipophilicity rank of the drugs.

4. It is concluded, therefore, that inhibition of mitochondrial lactate dehydrogenase is a property shared by most Class I anti‐arrhythmic drugs which may depend on their lipophilicity and possibly their membrane stabilizing effects.
EFFECTS OF ALDOSE REDUCTASE INHIBITION WITH EPALRESTAT ON DIABETES‐INDUCED CHANGES IN RAT ISOLATED ATRIA
Authors: Booth Richard J. , Hodgson Wayne C.
Published: June 2007

1. Isoprenaline and cardiac responsiveness of isolated atria from 2 and 6 week streptozotocindiabetic rats, and their age‐matched controls, was examined. The effects of chronic administration of epalrestat (40 mg/kg orally, by gavage) on diabetes‐induced changes were also investigated.

2. Spontaneously beating atria, bathed in either normal or high glucose (30 mmol/ L) Krebs’ solution, from both 2 and 6 week diabetic rats beat more slowly and with greater force than atria from control rats. These changes in basal parameters were normalized by 2 weeks of insulin (5 U/day s.c.) treatment but not by 2 or 6 weeks of chronic treatment with epalrestat.

3. Isoprenaline (0.1 nmol‐0.1 μmol/L) produced concentration‐dependent increases in inotropy and chronotropy in atria from both control and diabetic rats.

4. Atria from 2 week diabetic rats displayed decreased sensitivity to the positive inotropic effects of isoprenaline. This change was normalized by chronic insulin treatment but not by chronic epalrestat treatment.

5. Atria from 6 week diabetic rats displayed increased sensitivity to the positive chronotropic effects of isoprenaline which was normalized by epalrestat.

6. These results suggest that changes observed in atria from 2 week diabetic rats may be due to hyperglycaemia per se whereas in atria from 6 week diabetic rats abnormal activity of the polyol pathway may be a contributing factor.
THE EFFECT OF CROMAKALIM ON THE ELECTRICAL PROPERTIES OF AND [86Rb+] EFFLUX FROM NORMAL AND HYPERTROPHIED RAT BLADDER
Authors: Creed K. E. , Malmgren A.
Published: June 2007

1. The activity of smooth muscle strips from normal and hypertrophied rat bladders was compared. The hypertrophied bladders were produced by partially obstructing the urethra 8–13 weeks previously.

2. Spontaneous mechanical activity was more frequent and smaller in amplitude in strips from normal than hypertrophied bladders and was less sensitive to cromakalim, being reversibly abolished by cromakalim at 10−6 mol/L compared with 10−7 mol/L for hypertrophied bladder.

3. The mean resting membrane potentials of smooth muscle cells from normal and hypertrophied rat bladders were ‐47.2 and ‐47.6 mV, respectively. Bursts of spontaneous action potentials, corresponding to the mechanical activity, were seen in some cells.

4. Nifedipine at 10−6 mol/L had no significant effect on the resting membrane potential. Occasional single spikes occurred with increased duration and the afterhyperpolarization was abolished. Cromakalim at 10−5 mol/L produced hyperpolarization of 3–9 mV and, in the continued presence of the drug, occasional singe spikes could be recorded from both normal and hypertrophied bladders.

5. Nifedipine at 10−6 mol/L abolished movement but did not significantly alter [86Rb+] efflux from strips from either normal or hypertrophied bladders. Addition of cromakalim at 5± 10−6 or 5 ± 10−5 mol/L in the presence or absence of nifedipine increased efflux from the normal bladder by 30–40%. In the hypertrophied bladder the efflux increased by about 14% and 28% in the presence of 5 ± 10−6 and 5 ± 10−5 mol/L cromakalim, respectively.

6. No significant differences between electrical properties of normal and hypertrophied bladders were therefore found and we are unable to explain why the mechanical activity of hypertrophied rat bladders was more sensitive to cromakalim than normal bladders.
THE EFFECT OF ATRIAL NATRIURETIC PEPTIDE INFUSION ON RENAL HAEMODYNAMICS AND PLASMA LIPOPROTEINS IN PUROMYCIN AMINONUCLEOSIDE NEPHROSIS IN RATS
Authors: Radin M. Judith , McCune Sylvia A.
Published: June 2007

1. The effect of continuous intravenous administration of 1 UmUg/h atrial natriuretic peptide (ANP) for 4 days was studied in normal male Sprague‐Dawley rats and rats made nephrotic with puromycin aminonucleoside (PA).

2. ANP infusion significantly increased urinary sodium and potassium excretion by 3 days of infusion in control rats but not in PA‐treated rats. ANP infusion significantly increased glomerular filtration rate in PA‐treated rats, while effective renal plasma flow was similarly decreased compared with non‐infused nephrotic rats.

3. Plasma high density lipoproteins (HDL) were significantly decreased and low density lipoproteins (LDL) were increased in PA‐treated rats that received ANP; HDL were increased in normal rats infused with ANP.

4. Competitive binding studies demonstrated a lower density of specific ANP receptors in glomerular membranes from rats injected with PA, while binding affinity was unchanged.

5. Infusion with exogenous ANP did not promote natriuresis in PA nephrosis despite an enhancement of glomerular filtration rate (GFR), thus suggesting that sodium retention in this model is due to a post‐glomerular defect. Plasma lipoprotein composition in both normal and nephrotic rats may be affected by ANP.
EFFECTS OF RESERPINE ON THE CONTENT AND UPTAKE OF DOPAMINE AND NORADRENALINE IN RABBIT ARTERIES
Authors: Okada Keiji , Shinozuka Kazumasa , Shimoura Keiko , Kobayashi Yuta , Hattori Keisuke , Nakase Akira
Published: June 2007

1. Change with time of the content and uptake of dopamine (DA) and noradrenaline (NA) in the renal, superior mesenteric and femoral arteries and abdominal aorta of rabbit after reserpine administration was examined. Endogenous DA and NA were measured by high performance liquid chromatography coupled with electrochemical detector.

2. A single dose of reserpine (3 mg/kg, i.p.) maximally depleted the endogenous DA and NA contents in the four blood vessels 24 h after the administration; the ratios of reductions were 70–90% and approximately 90% of the normal levels, respectively. The DA contents in all four vessels recovered to the normal level within 4 days after reserpine. However, NA content did not recover to the normal levels within 30 days after reserpine except in the mesenteric artery.

3. The activity of dopamine β‐hydroxylase (DBH) significantly increased in all four blood vessels 1 h after reserpine. Although the DBH activity returned to the normal level after 3 days in the mesenteric artery, it returned within 24 h in the other three vessels.

4. [3H]‐Dopamine and [3H]‐NA uptake were almost completely depressed 1 h after reserpine. The [3H]‐NA uptake in four vessels recovered to the normal level 2–14 days after reserpine, and [3H]‐DA uptake recovered after 30–45 days. Thus, the endogenous DA content in blood vessels was completely restored although DA uptake and NA content were still affected.

5. These results suggested that the recovery of stored DA after reserpine was faster than that of stored NA and the recovery of DA uptake after reserpine was slower than NA uptake. This indicates a possibility that a part of DA pool may be different from NA pool in adrenergic nerve terminals in the blood vessels.
CHROMOSOME 17q23: A LOCUS FOR CARDIOVASCULAR DISEASE
Authors: Morris Brian J.
Published: June 2007

1. The gene for dipeptidyl carboxypeptidase 1 (angiotensin I‐converting enzyme, kininase II; DCP1), located on chromosome 17q23, has been implicated in hypertension in rats. In humans associations have been found for the insertion allele of a bi‐allelic insertion/deletion polymorphism of DCP1 with hypertension and the deletion allele with myocardial infarction. Other hypertension studies have, however, failed to find a relationship.

2. Mathematical predictions based on DCP1 association data suggest that high sib‐pair numbers may be needed to achieve statistical significance by this approach, although differences in the severity of hypertension in different study groups could account for the disparate findings.

3. No association was found between DCP1 allele or genotype frequencies and obesity in essential hypertensives.
METABOLISM OF URIDINE IN EXPANDED EXTRACELLULAR VOLUME STATES
Authors: Hasnain Quloobul , Macdonald Graham , Haupert Garner T.
Published: June 2007

1. Uridine and uridine monophosphate (UMP) are natriuretic and a vasopressor in intact rats. In deoxycorticosterone acetate (DOCA)‐salt hypertensive rats metabolic clearance rate (MCR) of uridine is raised and basal plasma uridine diminished, suggesting that metabolism of uridine is linked to changes in extracellular space.

2. Plasma uridine concentration was raised in 38 patients with chronic renal failure compared with age‐ and sex‐matched healthy controls (8.49 μmol/L, 4.37–13.74 μmol/L median, interquartile range, and 2.64 μmol/L 2.51–2.74 μmol/L, respectively, P < 0.001). Plasma uridine was significantly diminished after isotonic fluid removal by ultrafiltration (UF) from 7.25 μmol/L (3.7–11.08) to 5.07 μmol/L (3.3–8.3), P < 0.001, whereas concentration of marker solutes urea and creatinine remained unchanged. During haemodialysis (HD), plasma uridine fell significantly from its pre‐HD level.

3. In an animal model of expanded extracellular space the one‐kidney, one‐clip rat, plasma uridine was significantly higher (20.56±1.19 μmol/L, P < 0.01) and MCR diminished (34.93 ± 3.44 mL/kg per min, P < 0.01) compared with sham‐operated animals (plasma uridine 12.14 ± 1.07 and MCR 53.59 ± 4.11 mL/ kg per min). Uridine or UMP did not inhibit Na+, K+‐ATPase in either of the two assay systems.

4. It was concluded that catabolism of uridine is reduced by extracellular expansion and probably increased by volume reduction by UF. Such a function may be due to the presence of a hypertensive natriuretic factor postulated by Dahl and de Wardener (1980), but would not be consistent with the ouabain‐like factor postulated by other workers in this situation because it has no inhibitory effect on Na+, K+‐ATPase.
STIMULATION OF PHOSPHATIDYLINOSITOL TURNOVER IN ADULT RAT LEFT ATRIA DOES NOT INVOLVE RELEASE OF INOSITOL (1,4,5) TRI SPHOSPHATE
Authors: Anderson Karen E. , Myers Damian , Woodcock Elizabeth A.
Published: June 2007

1. The turnover rate of inositol (1,4,5) tris phosphate (Ins(1,4,5)P3) in noradrenaline‐stimulated adult rat left atria was calculated from changes in specific activity and was found to equal 110 ct/min per mg tissue. In contrast, the isomers of inositol mono‐ and bis phosphates accumulated at a rate of 508 ct/min per mg.

2. Neomycin, which inhibits release of Ins (1,4,5)P3, inhibited the accumulation of inositol phosphates in noradrenaline‐stimulated isolated neonatal cardiomyocytes but did not inhibit accumulation in left atria.

3. These data demonstrate that most of the inositol phosphates which accumulate in adult rat left atria do not derive from Ins (1,4,5) P3.

4. These data are best explained by a model in which noradrenaline stimulation results mainly in the breakdown of phosphatidylinositol(4)mono phosphate (PtIns(4)P1) to inositol(1,4)bis phosphate (Ins(1, 4)P2). Thus, heart tissue avoids the generation of Ins(1,4,5)P3.
SINGLE POINT ESTIMATION OF PLATELET ANGIOTENSIN II RECEPTOR NUMBER MAY NOT BE VALID SCREENING TEST FOR PREGNANCY‐INDUCED HYPERTENSION
Authors: Yang Y. , Pawlak M. A. , Macdonald G. J. , Duggan K. A.
Published: June 2007

1. Quantification of platelet angiotensin II (AII) receptors has been suggested as a screening test for pregnancy‐induced hypertension (PIH). Saturation analysis is too technically demanding to screen the requisite numbers and although a simplified method has been proposed, it has not been validated against saturation. This study sought to compare the two methods.

2. Platelet AII receptor number was determined by saturation analysis and from the specific binding at each of three radioligand concentrations. The two methods were compared by correlation and by plotting their differences against their means to determine limits of agreement.

3. Significant correlations were observed at all three radioligand concentrations; however, none of the regression lines approached the line of equality. There was increasing scatter as receptor number increased and 95% confidence intervals were too large to be clinically useful.

4. From this study it is concluded that the simplified method for estimating platelet AII receptor number is inaccurate and caution is urged in its use as a screening test for PIH.
ALTERED BLOOD PRESSURE, RENAL TUBULAR FUNCTION AND LEVELS OF CIRCULATING INHIBITORS OF Na‐K‐ATPase IN MATURE SHR EXPOSED TO LOW SALT DIET IN THE PERINATAL PERIOD
Authors: Nicolantonio R. Di , Walker L. L. , Harris P. J. , Amhian A. , Adam W. R. , Morgan T. O.
Published: June 2007

1. It has been shown previously that low salt diet, confined to the perinatal period only, reduces blood pressure (BP) and sodium retention in spontaneously hypertensive rat (SHR) offspring at maturity when compared with those given high salt diet.

2. In this study it is shown that such high salt diets are associated with an increased level of circulating Na‐K‐ATPase inhibitor (CINK) activity.

3. Animals given perinatal high salt diet have a significantly greater tubular reabsorptive capacity when compared with those given low salt diet.

4. The finding of a high level of circulating Na‐K‐ATPase inhibitory material in the face of increased renal tubular capacity and blood pressure suggests that while this inhibitory material may play a role in the elevated blood pressure of animals given high salt diet, it cannot cause the elevated rate of fluid reabsorption.
STEREOLOGICAL STUDIES ON MESENTERIC RESISTANCE ARTERY STRUCTURE IN NEW ZEALAND GENETICALLY HYPERTENSIVE AND CONTROL RATS
Authors: Ledingham J. M. , Millar J. A.
Published: June 2007

1. Stereological methods were used to quantitate and compare the structure of mesenteric resistance arteries (MRA) in New Zealand genetically hypertensive (GH) rats aged 4, 10 and 16 weeks and their normotensive control strain (N).

2. Blood pressure (BP) (tail‐cuff and intra‐arterial) were recorded before the vessels were fixed by perfusion and embedded in Technovit Kulzer GmbH D‐6393, Wehrheim, Germany).

3. Media and lumen volumes were measured on transverse sections (TS), by the Cavalieri method, and numbers of smooth muscle (SM) cells were estimated by the optical disector method.

4. There were no significant differences in lumen volume per unit vessel length between GH and age‐matched N groups at any age. However, at 10 and 16 weeks volume in GH groups was 9–10% lower than their respective N groups.

5. Media volume per unit vessel length increased in GH rats at all ages. The media/lumen ratio also increased in GH at all ages.

6. Smooth muscle cell density (SM cell number per unit volume of media) decreased in GH rats at all ages, i.e. there was no evidence of hyperplasia.

7. Blood pressure (tail‐cuff and intra‐arterial) significantly increased in GH rats at 4 weeks of age and also at 10 and 16 weeks.

8. These results show that media volume is increased in GH early in life, is not due to hyperplasia, but may be due to hypertrophy of the SM cells, an increase in the amount of extracellular matrix or a combination of both. However, since hypertension is also present at an early age, structural abnormalities cannot be said to be a primary cause of GH hypertension.
EFFECTS OF ENALAPRILAT ON SYMPATHETIC ACTIVITY AND METABOLISM OF EXERCISING MUSCLES IN RABBIT
Authors: Shimizu Kazumasa , Wang Zhi‐Qin , Way Diana J. , Palmos Jenny , McGrath Barry P.
Published: June 2007

1. To investigate the effects of angiotensin‐converting enzyme inhibition (ACEI) on exercise performance, the following were measured in eight normal rabbits performing graded treadmill exercise during intravenous vehicle saline or enalaprilat infusion: haemodynamics, noradrenaline (NA) spillover, hindlimb oxygen consumption and lactate release.

2. Blood pressure, heart rate (HR), femoral blood flow (FBF), hindlimb lactate release, hindlimb oxygen consumption and hindlimb NA spillover rate were all significantly increased during exercise and the changes during enalaprilat infusion were similar to control responses.

3. At submaximal exercise (6 m/min), ACEI did not significantly alter the responses of hindlimb lactate release, NA spillover rate or oxygen consumption. At the higher exercise load (12 m/min), ACEI reduced hindlimb NA spillover rate (33.1 ± 4.2 vs 61.3 ± 17.1 ng/min) and significantly increased oxygen consumption (241 ± 53.4 vs 133 ± 23.396, P < 0.05). The ratio of hindlimb NA spillover rate to total NA spillover rate was markedly increased during exercise, with similar changes being observed in ACEI and control experiments.

4. This study indicates that acute ACEI has a favourable effect on oxygen utilization in exercising muscle in the normal rabbit. Suppression of local sympathetic activation during exercising stress, as reflected in a reduced NA spillover response, may benefit the microcirculation in exercising muscles.
STRUCTURAL INFLUENCES ON RESISTANCE IN THE HINDLIMB VASCULAR BED OF THE RENAL HYPERTENSIVE RABBIT
Authors: Neilson J. A. , West M. J.
Published: June 2007

1. The contribution of arteriolar structural change to hindlimb vascular resistance was examined in the renal wrap hypertensive rabbit.

2. Haemodynamic variables were recorded at rest and after maximal vascular dilation using sodium nitroprusside and peripheral autonomic effector blockade. In the same animals at the end of experiments, morphometric measurements of hindlimb muscle arterioles were made.

3. Mean arterial pressure (MAP) and hindlimb vascular resistance were elevated in hypertensive animals compared with normotensive animals at rest and after maximal dilation.

4. Lumen area and lumen diameter were reduced whereas wall area and wall area to lumen area ratio were increased in hypertensive animals compared with normotensive animals.

5. In the renal wrap model of hypertension, the reduction in lumen area of arterioles, < 200 pm in diameter, is sufficient to explain the increase in haemodynamic resistance.
EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V1 RECEPTOR ANTAGONIST
Authors: Burrell L. M. , Phillips P. A. , Stephenson J. , Risvanis J. , Hutchins A‐M. , Johnston C. I.
Published: June 2007

1. This paper reports on the in vitro and in vivo characteristics of a non‐peptide vasopressin V1 receptor antagonist 1‐{1‐[4‐(3‐acetylaminopropoxy)benzoyl]‐4‐piperidyl}‐3,4‐dihydro‐2(1H)‐quinolinone (OPC‐21268).

2. OPC‐21268 caused a concentration‐dependent displacement of the selective V1 receptor antagonist radioligand, [125I]‐[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 ± 10‐8, 0.3 mol/L liver and 1.5 ± 10‐8, 0.2 mol/L kidney. OPC‐21268 had little effect on the selective V2 antagonist radioligand [3H]desGly‐NH29‐d(CH2)5[d‐Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10‐4 mol/L).

3. After oral administration to rats, OPC‐21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose‐dependent manner.

4. These studies confirm that OPC‐21268 is a potent non‐peptide, orally effective V1 vasopressin receptor antagonist.
EFFECT OF POSITIVE FAMILY HISTORY OF HYPERTENSION ON THE BLOOD PRESSURE AND CATECHOLAMINE RESPONSES TO A 6 HOUR ADRENALINE INFUSION
Authors: Bachmann Anthony W. , Ballantine Donna M. , Gordon Richard D.
Published: June 2007

1. The effects of 6 h infusions of adrenaline (INF‐A) or dextrose (INF‐D) and of post‐infusion cold pressor test (CPT) were compared in normal subjects, with (FH +) and without (FH ‐) a family history of hypertension.

2. Increased urinary excretion rates suggested facilitated noradrenaline (NA) release during and after INF‐A in both FH + and FH ‐.

3. Urinary adrenaline (U ADR) excretion increased during INF‐A, as expected, and was also slightly higher after INF‐A than INF‐D.

4. The effect of INF‐A on systolic blood pressure (SBP) was greater in FH — than in FH S but diastolic blood pressure (DBP) did not fall as quickly with nocturnal recumbency after INF‐A in FH +.

5. A significantly greater response in plasma NA to CPT was seen in FH + than in FH — after INF‐A. A similar trend was also seen after INF‐D.

6. Increases in DBP due to CPT were higher in FH + than in FH ‐ after both infusions.

7. This study provides evidence of increased noradrenergic activity during and after INF‐A, and also of a difference in response to sympathetic stimulation between FH + and FH ‐.
EFFECTS OF NITRO‐l‐ARGININE ON ENDOTHELIUM‐DEPENDENT RELAXATION OF CANINE CEREBRAL ARTERIES
Authors: Ohta Fumihito , Kobayashi Yuta , Shinozuka Kazumasa , Shimoura Keiko , Hattori Keisuke , Moritake Kouzo
Published: June 2007

1. The effect of NG‐nitro‐l‐arginine (NO2Arg) on the relaxation of canine basilar artery was investigated and compared with those of middle cerebral and femoral arteries.

2. NO2Arg (10−7‐3 × 10−5 mol/L) inhibited the substance‐P (Sub‐P; 10−12‐10−8 mol/L) induced relaxation in the basilar artery precontracted with prostaglandin F2α (PGF2α; 10−5 mol/L) or KCl (10−2 mol/L) in a concentration‐dependent manner and a ratio of the maximum inhibition by NO2Arg (3 × 10−5 mol/L) was more than 90%.

3. The relaxation induced by A23187 (10−9‐3 × 10−6) was also abolished by NO2Arg (3 × 10−5 mol/L), but that by glyceryl trinitrate (GTN; 10−9‐3 × 10−5 mol/L) was not, in the basilar artery precontracted with PGF2α (10−5 mol/L). NG‐nitro‐d‐arginine (NO2ArgD; 3 × 10−5 mol/L) did not affect the relaxation induced by Sub‐P (10−12‐10−8 mol/L).

4. l‐arginine (l‐Arg; 3 × 10−5‐10−4 mol/L) did not inhibit Sub‐P (10−12‐10−8 mol/L) induced relaxation in the basilar artery. Pretreatment of l‐Arg (10−4 mol/L) reversed the relaxation inhibited by NO2Arg (3 × 10−6 mol/L) in the arteries.

5. NO2Arg (3 × 10−5 mol/L) inhibited the Sub‐P (10−12‐10−8 mol/L) induced relaxation in the canine middle cerebral artery as much as in the basilar artery. NO2Arg (3 × 10−5 mol/L) also inhibited Sub‐P (10−12‐10−8 mol/L) induced relaxation in the femoral artery, but the degree of the inhibition was less than that in the basilar artery.

6. These results suggest that the endothelium‐derived relaxing factor (EDRF) of canine basilar artery is mainly l‐Arg derived nitric oxide which may play a more important role in the basilar artery than the femoral artery.
MONOCLONAL ANTIBODIES TO ARGININE VASOPRESSIN RECEPTOR BIND TO LIVER, KIDNEY AND PITUITARY MEMBRANES
Authors: Trinder Deborah , Mooser Vincent , Phillips Paddy A. , Smith A. Ian , Casley David , Johnston Colin I.
Published: June 2007

1. A vasopressin binding protein purified from rat liver membranes was used to immunize Balb/c mice and, subsequently, for the screening of hybrids raised in two different cell fusions.

2. Three hybrids were obtained which secreted monoclonal antibodies (MoAb) that bound to the purified solubilized receptor as detected by an enzyme‐linked immunosorbent assay technique. All three MoAb immunoprecipitated the purified receptor.

3. In addition, the MoAb bound in a concentration‐dependent manner to crude liver, kidney and anterior pituitary membranes, tissues known to contain arginine vasopressin (AVP) receptors but not to cardiac ventricle membranes which lack AVP receptors.

4. However, the binding of [125I]‐[d(CH2)5, Sar7]AVP (a specific radiolabelled V1 antagonist) to the membrane‐bound receptor was not inhibited by these antibodies.

5. These results suggest that MoAb recognize epitopes which are common to rat liver, kidney and anterior pituitary membranes but are not at the ligand binding site.
FIVE YEAR PROSPECTIVE STUDY ON BLOOD PRESSURE AND MAXIMAL OXYGEN UPTAKE
Authors: Sawada Susumu , Tanaka Hiroaki , Funakoshi Mitu , Shindo Munehiro , Kono Suminori , Ishiko Toshihiro
Published: June 2007

1. The relationship between physical fitness (maximal oxygen uptake Vo2max) and incidence of hypertension was investigated through a prospective study for a total of 16525 human‐years of observation.

2. This study involved 3305 Japanese males whose blood pressure (BP) was normal when they received their first physical examination before the age of 50. They were monitored from 1983 to 1988. The BP of 425 subjects was diagnosed as hypertension in the fifth year.

3. Fitness levels were divided into quintiles according to Vo2max levels, and were compared with the changes of BP and relative risk of hypertension after adjustment for age, initial percentage of body fat (PFAT), initial BP, alcohol consumption, cigarette smoking status and familial history of hypertension. The increase in BP of subjects in the least fit group was higher than in any other group. Relative risk was calculated using a multiple logistic regression and was 1.9 × higher in the least fit group compared with the fittest group.

4. The subjects were classified into three groups: the improved Vo2max group, the deteriorated Vo2max group and the unchanged Vo2max group. The increase in BP of the improved Vo2max group was significantly lower than the other two groups after adjustment for changes in PFAT, age, initial PFAT, initial BP, fitness level, alcohol consumption, cigarette smoking status and familial history of hypertension.

5. It is concluded that low Vo2max level is related to higher incidence of hypertension. An improved Vo2max would therefore be able to prevent hypertension.
ANTI‐ARRHYTHMIC EFFECTS OF A NEW CALCIUM ANTAGONIST, MONOTEPIL, AJ‐2615, IN EXPERIMENTAL ARRHYTHMIC MODELS
Authors: Yamamoto T. , Hosoki K. , Karasawa T.
Published: June 2007

1. To characterize the anti‐arrhythmic properties of a new calcium antagonist, monotepil, AJ‐2615, the preventive effects of AJ‐2615 were compared with those of the existing calcium antagonists, diltiazem and verapamil, in experimental models of arrhythmia.

2. AJ‐2615 (0.1–3.0 mg/kg, i.v.) suppressed ventricular arrhythmias induced by adrenaline (10 μg/kg, i.v.) in rats. AJ‐2615 (0.1 mg/kg per min for 2 min, i.v.) also suppressed atrial tachycardia induced by aconitine (0.01% aconitine solution) in rats.

3. In these activities, AJ‐2615 was comparable to or more potent than diltiazem and verapamil which are widely used for the treatment of arrhythmia.

4. In pro‐arrhythmic activity, AJ‐2615 was less potent than diltiazem and verapamil.

5. These results suggest that AJ‐2615 would be a safer anti‐arrhythmic agent, with less proarrhythmic liability than diltiazem and verapamil.
CHARACTERISTIC LOCALIZATION OF α1‐ and α2‐ADRENOCEPTORS IN THE HUMAN KIDNEY
Authors: Minamisawa Kohsuke , Umemura Satoshi , Hirawa Nobuhito , Hayashi Shuichi , Toya Yoshiyuki , Ishikawa Yoshihiro , Yasuda Gen , Ishii Masao
Published: June 2007

1. The localization of α‐adrenoceptors in the plasma membranes of human kidney were investigated by radioligand binding, using an α1‐antagonist, [3H]‐bunazosin, and an α2‐antagonist, [3H]‐rauwolscine.

2. Both the maximum binding (Bmax) and dissociation constant (Kd) of [3H]‐bunazosin were greater in the cortex than in the medulla. The Bmax of [3H]‐rauwolscine in the medulla was greater than in the cortex.

3. Thus, α1‐adrenoceptors appeared to be localized predominantly in the cortex, while the α2‐adrenoceptors were mainly present in the medulla of the human kidney.
ATRIAL AND BRAIN NATRIURETIC PEPTIDE RESPONSE TO EXERCISE IN PATIENTS WITH ISCHAEMIC HEART DISEASE
Authors: Nicholson Sarah , Richards Mark , Espiner Eric , Nicholls Gary , Yandle Tim
Published: June 2007

1. The response of venous plasma natriuretic peptides (atrial natriuretic peptide, ANP, and brain natriuretic peptide, BNP) plasma cyclic guanosine monophosphate (cGMP) and vasoactive hormones to dynamic exercise has been studied in 16 subjects undergoing diagnostic exercise tolerance for ischaemic heart disease (IHD), and in five healthy control subjects.

2. In patients with IHD, plasma ANP increased 3‐fold (mean 16 ± 2.5 pmol/L pre‐exercise, 51 ± 11 pmol/L after exercise, P<0.01). Increase in plasma BNP (10.5 ± 1.6 pmol/L pre‐exercise, 13 ± 2 pmol/ L after exercise, P<0.01) was proportionately much less than ANP but more sustained. In exercising normal subjects, plasma ANP levels doubled (P<0.01) but there was no significant change in plasma BNP levels.

3. In patients with IHD, there was a significant correlation between levels of plasma ANP and BNP before exercise (r = 0.97, P<0.001) as well as during exercise (r= 0.79, P<0.001).

4. Hormone responses in patients with positive exercise tests did not differ significantly from those with negative tests.

5. Although resting levels of plasma ANP and BNP in IHD are correlated, the findings indicate different mechanisms of secretion. The low BNP/ ANP ratio in response to acute dynamic exercise presumably reflects the predominance of ANP in pre‐secretory atrial stores.
SHEEP HYPOTHALAMUS CONTAINS A NON‐ANGIOTENSIN LIGAND FOR TYPE 1 AND TYPE 2 ANGIOTENSIN II RECEPTORS
Authors: Blasioli Julie , Kladis Athena , Clarke Iain J. , Campbell Duncan J.
Published: June 2007

1. The aim of this study was to determine whether the brain contains an alternative ligand for angiotensin II (AII) receptors.

2. A radioreceptor assay based upon bovine cerebellar membranes (Type 2 AII receptors) was used to monitor the partial purification of an AII‐like material from sheep hypothalami.

3. This material displaces 125I‐[Sar1, Ala8I‐AII from both type 1 (rat adrenal capsuIar membranes) and Type 2 AII receptors in a manner parallel to that of AIL It has a size of ∼30000 Da, is strongly cationic, is stable to boiling but is destroyed by trypsin. It is not recognized by AII antisera.

4. These data provide direct evidence for a non‐angiotensin endogenous ligand for brain AII receptors. This novel ligand may play a role in the regulation of blood pressure and other actions mediated by brain AII receptors.
DEMONSTRATION OF DEFECTIVE GLUCOSE UPTAKE AND STORAGE IN ERYTHROCYTES FROM NON‐INSULIN DEPENDENT DIABETIC PATIENTS AND EFFECTS OF METFORMIN
Authors: Yoa René G. , Rapin Jean R. , Wiernsperger Nicolas F. , Martinand Albert , Belleville Ivan
Published: June 2007

1. Red blood cells can store glucose and may thus participate in blood glucose homeostasis. We investigated if a defect in this process exists in non‐insulin dependent diabetes (NIDD).

2. Blood was obtained in fasting conditions from 10 normal and 10 newly diagnosed NIDD patients (before and after 4 weeks Metformin therapy). Washed erythrocytes were resuspended in media containing various glucose concentrations (4.4, 6.6, 8.8 and 13.2 mmol/L). Total glucose uptake was calculated as the sum of the measurements of lactate as well as free glucose, the latter being determined before and after addition of amyloglucosidase to the pellet.

3. Cells from diabetics showed a pronounced reduction in glucose uptake, particularly in their capacity to store glucose as glycogen (reactive to amyloglucosidase). Metformin treatment almost normalized glycogen levels, whereas lactate declined concomitantly in the pellet.

4. Our data demonstrate that a defect in glucose uptake exists in erythrocytes from NIDD patients, affecting both free and stored glucose, and that this defect is reversed by Metformin treatment, indicating that this drug can increase glycogen levels even in insulin‐insensitive cells.

5. Thus, in view of their total mass, erythrocytes may be important in the impaired glucose homeostasis in NIDD, in particular in marked hyperglycaemia such as after a meal.
INTRALYMPHOCYTIC FREE CALCIUM AND MAGNESIUM IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND EFFECTS OF BLOOD PRESSURE AND VARIOUS ANTIHYPERTENSIVE AGENTS
Authors: Adachi Minoru , Nara Yasuo , Mano Masayuki , Ikeda Katumi , Horie Ryoichi , Yamori Yukio
Published: June 2007

1. Free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured in peripheral lymphocytes from stroke‐prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar‐Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents‐treated SHRSP, and from secondary hypertensive WKY.

2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i.

3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin‐converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i.

4. After 40‐day administration of NG‐nitro‐l‐arginine (l‐NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the l‐NNA treated and non‐treated groups.

5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of divalent cation handling.
PHARMACOLOGICAL ACTIONS OF THE COENZYMES NAD(H) AND NADP(H) ON THE RAT ANOCOCCYGEUS MUSCLE
Authors: Najbar A. , Li C. G. , Rand M. J.
Published: June 2007

1. The pharmacological actions of the oxidized and reduced forms of nicotinamide‐adenosine dinucleotide (NAD, NADH) and nicotinamide‐adenosine dinucleotide phosphate (NADP, NADPH) were studied on rat isolated anococcygeus muscles.

2. The actions of the two nucleotides were different, but there were no apparent qualitative differences between the oxidized and reduced forms of each.

3. In fully relaxed anococcygeus muscles, NADP(H) produced transient contractions that were subject to desensitization, but NAD(H) had no effect.

4. NADP(H) slightly enhanced contractions elicited by noradrenergic nerve stimulation. In contrast, noradrenergic contractions were inhibited by NAD(H). NADH reduced the stimulation‐induced release of noradrenaline, but enhanced contractions elicited by exogenous noradrenaline.

5. In anococcygeus muscles partly contracted with guanethidine, NAD(H) produced a further sustained increase in tone; in contrast, NADP(H) mainly produced transient relaxations to which there was immediate desensitization.

6. Relaxations of anococcygeus muscle elicited by nitrergic nerve stimulation were not affected by NAD. In contrast, NADP(H) reduced them.

7. The actions of NAD(H) were generally the same as those of adenosine and can be attributed to activation of P1‐purinoceptors since they were blocked by the selective antagonist 8‐sulphophenyl‐theophylline.

8. The actions of NADP resembled those of the P2‐purinoceptor agonist ATP to some extent, but there were some differences. As suggested by others, NADP may act on a unique receptor.