bluuebunny/crossref_metadata_2025 huggingface dataset:
METHOD OF MEASURING LIQUID JUNCTION POTENTIALS IN SMALL (NANOLITRE) DROPLETS OF BIOLOGICAL FLUIDS
Authors: Sugo E. , Györy A. Z.
Published: June 2007

1. A method is described which allows the determination of liquid junction potentials between biological fluid samples of less than 1 nL with a reproducibility of 10%. This was achieved by use of a micro‐method and the use of 3% agarose added to the electrolyte in the measuring electrodes.

2. Validation was performed with a modified flowing boundary method and the system was also tested using a solution containing divalent ions. Liquid junction potential between surface fluid from rat kidneys and harvested renal proximal tubular fluids was‐0.62 ± 0.11 mV (mean ± s.d., n= 66).
ACTIONS OF SOME AUTACOIDS AND PEPTIDES, INCLUDING RELAXIN, ON COSTO‐UTERINE MUSCLE FROM RATS
Authors: Fox D. , Handberg G. M. , Hartley M. L. , Monagle J. , Pennefather J. N.
Published: June 2007

1. The actions of angiotensin II, bradykinin, oxytocin, arginine vasopressin, relaxin, serotonin and the prostaglandins E2 and F2α were examined on preparations of costo‐uterine muscle from stilboestrol‐treated rats.

2. All the agonists, except relaxin, when used in concentrations which contract the rat uterus, also produced contractions of costo‐uterine muscles. Concentration‐response curves were steep and maximal responses to the agonists were comparable. The negative log molar EC50 values were: serotonin, 6.5; angiotensin II, 8.8; bradykinin, 8.4; PGE2, 8.3; PGF2α, 7.1. The EC50 values (units/L) for oxytocin and vasopressin were 4.4 and 2.7 respectively.

3. Indomethacin (2.8 or 5 μmol/L) did not decrease the contractile effects of the peptides or serotonin. The effects of serotonin were reduced, but not reversed, by methysergide (0.94 μmol/L).

4. Porcine relaxin inhibited field stimulation‐induced contractions of costouterine muscle and uterine horns from immature rats pretreated with oestradiol cypionate and from stilboestrol‐treated mature rats. It was much less potent, and its effects were less clearly concentration‐related, on costo‐uterine muscle.

5. The inhibitory effects of relaxin on the uterus were unaffected by propranolol (1 μmol/L), confirming that on this tissue relaxin acts independently of the release of catecholamines. Progesterone (30 μmol/L) was also without effect on the action of relaxin on the uterus.

6. These results taken together indicate that the costo‐uterine muscle of the rat: (i) contracts in response to serotonin and the peptides angiotensin II, arginine vasopressin, bradykinin and oxytocin independently of the release of the contractile prostaglandins F2α and E2; and (ii) in contrast to the uterus, may lack a significant population of receptors for relaxin. These differences from the whole uterine horn of this species may reflect the absence of endometrial tissue, and/or of sensitivity of the smooth muscle cells of the costo‐uterine muscle to oestrogen.
RENAL HYPER‐RESPONSIVENESS TO BLOOD VOLUME EXPANSION IN BRATTLEBORO RATS IS NOT RELATED TO PLASMA ANF IMMUNOREACTIVITY
Authors: Palluk Rainer , Veress Anthony T. , Sonnenberg Harald
Published: June 2007

1. Anaesthetized homozygous Brattleboro (DI) rats were used to study the renal response to iso‐oncotic blood volume expansion.

2. With the same degree of hypervolaemia DI rats had exaggerated diuresis, natriuresis, and chloriuresis, but not kaliuresis, compared with heterozygous control rats. This increased excretion resulted in negative water balance by the end of the experiment in DI rats, whereas the controls showed restoration of normal balance. The control rats retained significant amounts of sodium and chloride, the Brattleboro rats, however, did not.

3. The lithium clearance method was used to localize the defect in sodium reabsorption. As judged from this method, there was a significantly lower sodium reabsorption in the proximal tubules as well as in the distal parts of the nephron of DI rats.

4. Plasma immunoreactivity of atrial natriuretic factor (ANF) was not different between groups before volume expansion. ANF levels rose and fell similarly in both groups during and after the iso‐oncotic infusion.

5. Our results demonstrate that DI rats respond to acute hypervolaemia with an exaggerated diuresis and saluresis. The mechanism of the increased salt excretion may involve inhibition of sodium transport in the proximal tubules as well as in the distal parts of the nephron. These transport defects are not dependent on differing plasma ANF levels.
WHOLE BLOOD AGGREGATION AND PLASMA LYSO‐PAF RELATED TO SMOKING AND ATHEROSCLEROSIS
Authors: Sturm Marian J. , Strophair Julie M. , Kendrew Phillip J. , Vandongen Robert , Beilin Lawrence J. , Taylor Roger R.
Published: June 2007

1. Aggregation of diluted whole blood (impedance method) and thromboxane B2 production during aggregation were measured in cigarette smokers and non‐smokers, aged 41–68 years, with (n= 14) and without (n= 15) major symptomatic peripheral vascular disease. The plasma level of the lyso derivative of platelet activating factor (lyso‐PAF) was also measured using a bioassay with 14C‐serotonin labelled rabbit platelets, after extraction and acetylation to active PAF.

2. Aggregation to ADP and collagen was significantly less in non‐smokers without vascular disease (n= 8) than in the other three groups (P < 0.01; ANOVA). Thromboxane B2 production was not significantly different between the groups. There was no significant difference in plasma lyso‐PAF between groups. No change was found in any variable after smokers smoked two cigarettes.

3. In these older age subjects, both vascular disease and the smoking habit were associated with greater whole blood aggregation. However, current smoking and the smoking of two cigarettes did not affect aggregation in subjects with vascular disease and plasma lyso‐PAF levels were not consistently related to either smoking or vascular disease.
EFFECTS OF ATRIAL NATRIURETIC FACTOR ON CYCLIC GMP CONTENT IN THE RAT AORTIC SMOOTH MUSCLE: STUDIES ON THE ROLE OF MEMBRANE Na+,K+‐ATPase
Authors: Hegde Sharath S. , DeFeo Maria L. , Jandhyala Bhagavan S.
Published: June 2007

1. These studies were conducted to determine whether preservation of the functional integrity of the membrane, Na+,K+‐stimulated ATPase is essential for the atrial natriuretic factor (r‐ANF‐8–33) to enhance guanosine 3′,5′‐monophosphate (cGMP) content in the rat aortic smooth muscle. In freshly dissected rat aortic tissues, levels of cGMP were estimated using radioimmunoassay.

2. ANF (0.1 μmol/L in Krebs‐Henseleit media) produced significant elevation in cGMP levels in the aortic smooth muscle when compared with that incubated in the control media, whereas suppression of Na+‐pump with ouabain (1.0 mmol/L) and/or K+‐free media did not produce any significant changes in the basal cGMP level; these two experimental manoeuvres did not prevent enhancement of cGMP by ANF.

3. Incubation of the tissues in the media containing ouabain plus vasoconstrictor concentrations of norepinephrine (0.3 μmol/L) also did not alter basal cGMP levels and did not prevent the ability of ANF to elevate cGMP.

4. These studies demonstrate that the antagonism by ouabain, of vasorelaxant effects of ANF (as reported in the literature) are not due to the prevention of the ability of ANF to enhance cGMP levels in the arterial smooth muscle. It is proposed that such an antagonism may be related to the actions of ouabain and ANF on diverse, and perhaps independent, mechanisms which affect Ca2+‐fluxes across the cell membrane.
COMPARISON OF THE VASCULAR AND GLOMERULAR CHANGES IN AORTIC‐LIGATURE AND DOCA‐SALT HYPERTENSION
Authors: Hewitson Tim , Kamitsuji Hidekazu , Whitworth Judith A. , Kincaid‐Smith Priscilla
Published: June 2007

1. Animals and histology from two previous investigations were used to test the hypothesis that a similar elevation in blood pressure may result in a different sequence of pathological changes in different experimental models of hypertension, DOCA‐salt and aortic‐ligature hypertension.

2. To assess differences in morphological parameters, individual animals in the two groups were paired (n= 12) for the same level of blood pressure at sacrifice.

3. Vascular damage was significantly less in the DOCA‐salt group (P < 0.01). Glomerular lesions however were more severe in the DOCA‐salt group. In rats with aortic‐ligature hypertension significantly fewer glomeruli had fibrinoid and/or crescents than in DOCA‐salt rats (P < 0.001). There were fewer glomeruli with epithelial cell droplets (ECD) and fewer ECD per glomerulus in aortic‐ligature when compared with DOCA‐salt hypertension (P < 0.001, P < 0.001, respectively).

4. This study highlights the significance of factors other than blood pressure per se in producing vessel and glomerular lesions in experimental hypertension.
A METHOD FOR EXAMINING TURNOVER AND SYNTHESIS OF PALMITATE‐CONTAINING BRAIN LIPIDS IN VIVO
Authors: Robinson Peter J. , Rapoport Stanley I.
Published: June 2007

1. A theoretical three compartment model is presented which gives the rate of incorporation of plasma palmitate into brain, Jpalm, in terms of turnover and synthesis of palmitate‐containing lipids, de novo synthesis of palmitate from acetate, and recycling of palmitate within lipids.

2. Jpalm equals 4 h brain radioactivity following intravenous injection of [U‐14C]‐palmitate (determined with quantitative autoradiography), divided by integrated plasma specific activity of palmitate. Jpalm follows the time course of brain lipid synthesis during development of the rat, but is age‐invariant in the adult.

3. At 1–7 days after 5 min of bilateral carotid occlusion in the awake gerbil, intravascular [14C]‐palmitate incorporation is reduced in the CA1 pyramidal layer of the hippocampus, consistent with delayed neuronal death, but is elevated in the CA3 and CA4 pyramidal layers and dentate gyrus, suggesting synthesis of new membrane during recovery from the ischaemic insult.

4. Several weeks after unilateral destruction of the cochlea in 11 day old rats, incorporation of [14C]‐palmitate from plasma into appropriate central auditory regions is reduced, corresponding to reduced cell size and altered morphology.

5. [14C]‐palmitate incorporation into the left hypoglossal nucleus is increased during and following axonal regeneration (up to 23% compared with control side) following transection of the left hypoglossal nerve in Fischer‐344 rats, whereas incorporation is decreased 6–7% when regeneration is prevented. Time courses of incorporation in both cases correspond to histological changes.

6. The results show that the palmitate method can be used to examine regional turnover and synthesis of brain lipids following injury, sensory deprivation, development, regeneration and ageing.
NIFEDIPINE IN CORTICOSTEROID‐DEPENDENT ASTHMA: PRELIMINARY STUDY
Authors: Al‐Waili Noori S.
Published: June 2007

1. To test whether nifedipine reduces corticosteroid requirements of patients with asthma, a 16‐week double‐blind crossover trial comparing nifedipine with placebo was performed.

2. Eight females and seven males with corticosteroid‐dependent asthma were studied, ranging in age between 20 and 65 years (mean = 45 years).

3. Results showed that in 12 of 15 patients, nifedipine caused significant reduction in corticosteroid requirements when compared with placebo (P < 0.01). No side‐effects were reported apart from mild headache and leg oedema observed in a few patients receiving nifedipine.

4. It could be concluded that nifedipine has a steroid‐sparing effect in steroid‐dependent asthma.
INTERRELATIONSHIP BETWEEN CORTISOL AND ATRIAL NATRIURETIC FACTOR IN THE IMMATURE OVINE FETUS
Authors: Wintour E. Marelyn , Cooper Elizabeth , McDougall John G. , Shine Peter F. , Towstoless Michelle K.
Published: June 2007

1. In chronically cannulated ovine fetuses (100–130 days of gestation) the infusion of cortisol (86.7 ± 15 μg/h for 4 h) or human atrial natriuretic factor (ANF; 4.4 μg for 2 h) resulted in highly significant increases in the excretion of sodium, chloride, potassium and water.

2. Cortisol had no significant effect on fetal plasma ANF concentrations. All values are mean and s.e.m. Plasma immunoreactive ANF was 53 ± 5 and 67.3 ± 13 pmol/L in the 4 h saline infused fetuses, and 51.3 ± 14.3 and 74 ± 13.3 pmol/L in cortisol‐infused fetuses (n= 7). A separate group of fetuses received 2 h infusions of saline or hANF (4.4 ug/h), and plasma IR‐ANF values were measured (n= 3). The values, at 0, 60, 90 and 120 min were, respectively, 19.7 ± 3, 17.3 ± 0.7, 18.7 ± 3.7 and 20.7 ± 3.7 pmol/L in the saline infused group, and 25.3 ± 5.3, 80.7 ± 32.3, 123.3 ± 4.3 and 100 ± 15 pmol/L in the ANF‐infused fetuses.

3. Blood cortisol concentrations, in fetuses infused for 4 h with 0.9% NaCl, were 3.1 ± 0.8 nmol/L (n= 7); in fetuses infused with 0.9% NaCl for 2 h were 3.6 ± 1 nmol/L (n= 3); in fetuses infused for 4 h with cortisol were 19.9 ± 1.9 nmol/L (n= 7); and in fetuses infused with hANF for 2 h were 6.0 ± 3.0 nmol/L (n= 5).

4. There was no effect of fetal hANF infusion on maternal or fetal blood aldosterone concentrations.

5. The conclusion of this study was that cortisol and ANF cause natriuresis and diuresis in the immature ovine kidneys by independent mechanisms.
STUDY OF THE INHIBITORY EFFECT OF LEAD ACETATE ON DUODENAL CONTRACTILITY IN RAT
Authors: Karmakar N. , Anand S.
Published: June 2007

1. Abdominal colic and constipation are symptoms of lead poisoning in man, but mechanisms of these effects are not yet fully understood. In this study the effect of lead acetate on contractility of rat duodenum was determined in vivo in 70 rats.

2. Rats were orally dosed with 44 mg/kg per day lead as 53 mmol/L lead acetate, for 4 weeks. Motility of the duodenum was recorded with an electrical impedance probe.

3. A significant decrease in the amplitude of contraction waves in case of treated rats was observed compared with controls which received an equal volume of saline. The number of contractions increased from 26 per min in controls to 33 per min in treated rats. Gastrointestinal transit rate decreased by 64% and 69% after 9 and 15 days of lead exposure, respectively.
EFFECT OF SOME DRUGS ACTING AT THE CENTRAL‐TYPE BENZODIAZEPINE RECEPTORS ON BLOOD GLUCOSE IN MICE
Authors: Najim Rafid A. , Al‐Essa Luay Y. , Al‐Jawad Faruk H.
Published: June 2007

1. The effects of some drugs acting at the central‐type benzodiazepines receptors on blood glucose levels in mice were studied.

2. Clonazepam, injected intraperitoneally in doses of 0.625–5 mg, produced a dose‐dependent increase in blood glucose 30 min after administration.

3. The hyperglycaemic effect of clonazepam (2.5 mg/kg, i.p.) was dose‐dependently reduced by Ro 15–1788 (10–40 mg/kg, i.v.), a benzodiazepine antagonist.

4. Ro 5–3663, a GABA antagonist which may act at the picrotoxinin site, produced a significant increase in blood glucose (5 or 10 mg/kg, i.p.); however, when given together with clonazepam (2.5 mg/kg, i.p.) attenuation of the hyperglycaemic effect was observed.

5. Pk 8165, a partial agonist, lacked an effect on blood glucose over the dose range of 5–20 mg/kg, i.p. but caused a slight increase in blood glucose in a dose of 40 mg/kg, i.p.
FACILITATION OF NORADRENALINE RELEASE BY ISOPRENALINE IN RAT ISOLATED ATRIA DOES NOT INVOLVE ANGIOTENSIN II FORMATION
Authors: Mian M. A. , Majewski H. , Rand M. J.
Published: June 2007

1. Rat isolated atria were incubated with 3H‐noradrenaline and the intramural sympathetic nerves were stimulated at 2 Hz for 60 s. The stimulation‐induced (SI) efflux of radioactivity was used as an index of release of transmitter noradrenaline.

2. Isoprenaline (0.1 μmol/L) alone did not increase noradrenaline release. Cocaine (30 μmol/L) produced a 73% increase in the stimulation‐induced release of noradrenaline. In the presence of cocaine, isoprenaline enhanced noradrenaline release by 22%.

3. In the presence of cocaine, both angiotensin I (0.3 μmol/L) and angiotensin II (0.3. μmol/L) produced almost two‐fold enhancements in the SI release of noradrenaline.

4. Captopril (5 μmol/L) blocked the facilitatory effect of angiotensin I on nor‐adrenaline release but did not alter that of isoprenaline.

5. Saralasin (0.1 μmol/L) reduced the facilitatory effect of angiotensin II on noradrenaline release but did not alter that of isoprenaline.

6. The findings indicate that the facilitation of noradrenaline release by isoprenaline in rat atria is not mediated by local formation of angiotensin II.
ELIMINATION OF DIFLUNISAL AS ITS ACYL GLUCURONIDE, PHENOLIC GLUCURONIDE AND SULFATE CONJUGATES IN BILE‐EXTERIORIZED AND INTACT RATS
Authors: Dickinson Ronald G. , King Andrew R. , Verbeeck Roger K.
Published: June 2007

1. The disposition of diflunisal (DF) was investigated in both bile‐exteriorized and intact rats given 10 and 100 mg/kg doses intravenously (i.v.).

2. In addition to the phenolic glucuronide (DPG) and acyl glucuronide (DAG) conjugates, the sulfate conjugate (DS) was found to be a major metabolite. The glucuronides were excreted preferentially in bile, whereas DS was excreted almost exclusively in urine.

3. In bile‐exteriorized animals, recoveries of DPG, DAG and DS in bile were 12.2%, 23.8%, 0.4%, respectively, and in urine, 10.3%, 5.6% and 15.2%, respectively, at the 10 mg/kg dose; and in bile, 11.3%, 41.6% and 1.0% respectively, and urine 2.9%, 1.1% and 17.0%, respectively, at the 100 mg/kg dose.

4. Total plasma clearance of DF and formation clearance of DF to DPG were reduced at the higher dose, suggesting saturation of this glucuronidation pathway. Formation clearances of DF to DAG and DS were little affected by the dose change.

5. Considerable enterohepatic recirculation of DF was apparent from the prolongation of DF and its conjugates in plasma of rats with an intact bile flow into the gut. The net metabolic effect of such cycling was enhancement of overall DS formation, from 15.6% and 18.0% of the 10 and 100 mg/kg doses, respectively, in bile‐exteriorized rats to 28.5% and 42.1% of the doses respectively, in the intact animals.
REGIONAL DISTRIBUTION OF THE CARDIAC OUTPUT AND RENAL RESPONSES TO ATRIAL ATRIURETIC PEPTIDE INFUSION IN RABBITS WITH CONGESTIVE HEART FAILURE
Authors: Langton David , Jover Bernard F. , Trigg Lisbeth , Fullerton Meryl , Blake Duncan W. , McGrath Barry P.
Published: June 2007

1. A biventricular, low‐output congestive cardiomyopathy was induced in 19 rabbits by administering adriamycin (16 mg/kg). The effects of SaL‐rat atrial natriuretic peptide (ANP) infused at 0.1, 0.2 and 0.4 μg/kg per min, were then examined in terms of (i) central haemodynamics (ii) regional blood flow (iii) renal function and (iv) plasma norepinephrine and plasma renin.

2. In this dose range, ANP produced progressive and significant falls in stroke volume, cardiac output and mean arterial pressure, owing to a fall in venous return. The heart rate response to this was blunted.

3. Using radiolabelled microspheres, significant falls in the perfusion of cutaneous, gastrointestinal and musculoskeletal tissues were observed, due to reduced vascular conductances in these beds. These changes were accompanied by activation of the sympathetic nervous system as evidenced by a progressive rise in plasma norepinephrine. A significant increase in plasma renin was only observed with the highest infusion of ANP.

4. Renal blood flow was maintained in the face of a falling mean arterial pressure and cardiac output, but diuretic and natriuretic effects were absent.

5. It was concluded that the dominant influence of ANP infusion in this model of heart failure appeared to be a reduction in cardiac preload with detrimental overall haemodynamic consequences.
EFFECTS OF NEUROPEPTIDE Y ON BAROREFLEX CONTROL OF HEART RATE AND MYOCARDIAL CONTRACTILITY IN CONSCIOUS RABBITS
Authors: Minson R. B. , McRitchie R. J. , Chalmers J. P.
Published: June 2007

1. The effects of intravenous (i.v.) neuropeptide Y (NPY, 10 μg/kg bolus) on the stimulus‐response curves relating changes in heart period (HP) and in peak left ventricular (LV) dP/dt to acute changes in mean arterial pressure (MAP) were determined in conscious, normotensive rabbits.

2. The relationship between increases and decreases in MAP and the subsequent changes in HP were represented by a sigmoid‐shaped curve described by a logistic function. Following NPY administration there was a baroreflex‐dependent increase in the maximum slope (sensitivity) at the midpoint of this MAP‐HP curve from 7.0 ± 0.5 to 10.6 ± 1.3 ms/mmHg (P<0.05). NPY caused an upward shift in the whole curve which reflected the NPY‐induced bradycardia and was independent of baroreflexes.

3. The relationship between increases in MAP and decreases in peak LV dP/dt was determined during fixed‐rate atrial pacing to prevent the effects of the accompanying bradycardia. Increases in MAP and the corresponding reductions in peak LV dP/dt were represented by an exponential function.

The slope of the curve, measured at its origin 5–15 min after NPY administration, was reduced from −0.9 ± 0.2 to −0.4 ± 0.1 units (P<0.05).

4. The effects of NPY are consistent with an action on efferent connections of the arterial baroreceptor reflex, mediated through a reduction in cardiac β‐adrenergic tone. They would also be explained through actions on the afferent or central neural connections of the baroreflex.
CONTRACTILE RESPONSES TO α1‐ADRENOCEPTOR STIMULATION DURING MATURATION IN THE AORTA OF THE NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RAT: RELATION TO STRUCTURE
Authors: Sudhir Krishnankutty , Angus James A.
Published: June 2007

1. The significantly greater rise in blood pressure during the first 20 weeks of life in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar‐Kyoto rats (WKY) may be related to increased vasoconstrictor responses caused by enhanced transmitter release or post‐junctional receptor changes.

2. The reactivity of rat isolated aorta to post‐junctional α1‐adrenoceptor stimulation by methoxamine and to transmural sympathetic nerve stimulation was studied in ring segments suspended at equivalent transmural pressures in organ baths.

3. Wall stress in the SHR aorta was significantly higher at 4 weeks, but lower at 9 and 20 weeks when compared with the WKY aorta, a possible adaptation to the higher pressures seen in the SHR at the latter ages.

4. The sensitivity (location of EC50) to methoxamine was similar at all ages in both strains, but the SHR aortae at 9 and 20 weeks generated higher maximal contractile force to this agent compared with the WKY aorta.

5. The increase in force to methoxamine parallelled the medial hypertrophy of the SHR aorta, determined from computerized morphometric analysis.

6. There was an enhanced response to transmural field stimulation in the SHR aortae at 9 weeks, that was not accounted for by medial hypertrophy or altered neuronal uptake of noradrenaline.

7. These studies suggest that enhanced maximal contractile force in the SHR aorta to α1‐adrenoceptor stimulation is accounted for by medial hypertrophy. However, there is an additional enhanced reactivity at 9 weeks in response to nerve stimulation in the SHR aorta that may be related to increased innervation density.
DAILY VARIATION IN INFLUENCE OF LITHIUM ON SERUM CALCIUM CONCENTRATION: A PRELIMINARY REPORT
Authors: Fujimura Akio , Ohashi Kyo‐ichi , Ebihara Akio
Published: June 2007

1. One millilitre of 5% glucose (vehicle, n= 10) or 1 mL solution of lithium chloride (LiCl) (0.5 or 2.0 mmol/kg per day, n= 10 for each) was injected intraperitoneally in Wistar rats at 10:00 or 22:00 h for 6 days. Blood samples for ionized and total calcium were taken on day 7.

2. Mild elevations in ionized, but not non‐ionized (total‐ionized) calcium were observed following LiCl treatment in both administration times.

3. The increment in ionized calcium was greater when LiCl was injected at 22:00 h than when it was given at 10:00 h.

4. These data indicate that: (1) the influence of lithium on calcium metabolism varies with its administration time; and (2) mild hypercalcaemia induced by the agent mainly depends on the elevation in the ionized fraction of calcium.
EFFECTS OF CHRONIC CONVERTING ENZYME INHIBITION ON THE VASCULAR RENIN‐ANGIOTENSIN SYSTEM
Authors: Saito Hiroshi , Nakamaru Mitsuaki , Rakugi Hiromi , Mikami Hiroshi , Ogihara Toshio , Inagami Tadashi
Published: June 2007

1. The effects of chronic oral administration of inhibitors of angiotensin converting enzyme (ACE) on the vascular renin–angiotensin system were studied.

2. Male Sprague‐Dawley rats were treated orally with five ACE inhibitors, captopril, enalapril, ramipril, cilazapril and CS‐622 (10 mg/kg per day), for periods of 1–2 weeks. Their mesenteric arteries were then isolated and perfused in vitro with Krebs'‐Ringer solution, and the angiotensin II (AII) released into the perfusate was measured under unstimulated and isoproterenol‐stimulated conditions. The vascular renin activity was also determined after treatments with ACE inhibitors.

3. Treatment with captopril for 1 week suppressed the isoproterenol‐stimulated increase in All release, but had little effect on the baseline release. Oral treatment with captopril for 2 weeks or with other ACE inhibitors for 1 week markedly inhibited both the unstimulated and stimulated release of AII from the mesenteric vasculature.

4. Both the vascular renin activity and the plasma renin activity increased on captopril treatment, but their changes with time were different.

5. These results indicate that virtually complete inhibition of the vascular renin–angiotensin system can be achieved after prolonged treatment with ACE inhibitors, and suggest that the chronic antihypertensive action of ACE inhibitors is not solely due to inhibition of the plasma renin–angiotensin system.
INTRACEREBROVENTRICULAR INFUSIONS OF INSULIN INCREASE VASOPRESSIN RELEASE IN RATS
Authors: Nishimura Masato , Takahashi Hakuo , Matsusawa Makoto , Ikegaki Iwao , Nakanishi Tadashi , Hirabayashi Masami , Yoshimura Manabu
Published: June 2007

1. The role of cerebral insulin or insulin‐like immunoreactive substance (ILI) on arginine–vasopressin (AVP) release using rats was investigated. Feeding rats with a high salt diet for 4 weeks significantly decreased the contents of ILI in both the hypothalamus and pituitary gland. Intracerebroventricular infusions of insulin (4 and 40 μg/min for 30 min) increased plasma AVP concentrations dose‐dependently without hypoglycaemia, but decreased hypothalamic and pituitary contents of AVP.

2. These results indicate that ILI in the brain may play a role in the secretion of AVP, and that this mechanism could be operated to control a water–sodium balance.
DOES VERAPAMIL LIMIT MYOCARDIAL INFARCT SIZE IN A HEART DEFICIENT IN XANTHINE OXIDASE?
Authors: Adachi Takeo , Miura Tetsuji , Noto Tetsuya , Ooiwa Hitoshi , Ogawa Takashi , Tsuchida Akihito , Iwamoto Toshihiro , Goto Mahiko , Iimura Osamu
Published: June 2007

1. The delay of ischaemic myocardial necrosis by verapamil has been reported in the dog heart, which contains a high level of xanthine oxidase, a potential source of cytotoxic free radicals. To test whether the retardation of ischaemic myocyte death by verapamil is not an isolated phenomenon in the xanthine oxidase rich heart, we assessed the effect of verapamil in the rabbit heart, which lacks xanthine oxidase.

2. Verapamil (200 μg/kg, i.v. bolus plus 40 μg/kg per min) was administered in a group of rabbits (n= 5) to test the haemodynamic response to this agent. The heart rate, blood pressure and left ventricular dp/dt max were reduced by 11, 25 and 57%, respectively, and the plasma concentration of verapamil was maintained at 300–400 ng/mL during the infusion.

3. In other groups of rabbits, the effect of the same dosage of verapamil on the size of myocardial infarct after 20 or 30 min ischaemia and 72 h reperfusion was examined. The verapamil was administered for 45 min, starting 15 min prior to ischaemia. The percentage of area at risk infarcted (%I/AAR) was 15.2±3.9% in the 20 min ischaemia control group and 15.4±4.5% in the 20 min ischaemia verapamil group, 49.1±3.4% in the 30 min ischaemia control group and 41.2±3.3% in the 30 min ischaemia verapamil group. The %I/AAR was significantly smaller in the 20 min ischaemia control groups and 15.4±4.5% in the 20 min ischaemia there was no difference in %I/AAR between the control and verapamil treated animals in either the 20 or the 30 min ischaemia groups.

4. These results suggest that verapamil does not delay the transition from reversible to irreversible myocardial injury during coronary occlusion in the rabbit, which like the human, lacks myocardial xanthine oxidase.
EFFECTS OF HALOTHANE, KETAMINE, PROPOFOL AND ALFENTANIL ANAESTHESIA ON CIRCULATORY CONTROL IN RABBITS
Authors: Van Leeuwen Andrew F. , Evans Roger G. , Ludbrook John
Published: June 2007

1. We have made a within‐rabbit comparison of the effects of four general anaesthetic regimens on the haemodynamic response to acute reduction in central blood volume and on baroreflex control of heart rate.

2. Acute haemorrhage was simulated by gradually inflating a cuff on the inferior vena cava in order to cause cardiac output to fall at a constant rate of 8.5%/min while the responses of systemic vascular resistance, arterial pressure and heart rate were measured. The full range of the baroreceptor–heart rate reflex was elicited by inflating aortic and vena caval cuffs. These indices of circulatory control were repeatedly measured within five protocols, to which each rabbit was exposed in randomized order.

3. In each protocol the rabbit was first studied unanaesthetized. Then a small dose of thiopentone sodium was given (16 mg/kg). In the four main protocols the rabbit was then intubated and ventilated, first with 100% oxygen and then with 50% nitrous oxide, during administration of one of four anaesthetic agents. These were halothane (2.0 and 2.5%), ketamine (2.5 mg/kg per min), propofol (0.83 and 1.25 mg/kg per min) and alfentanil (2.5 and 3.33 μg/kg per min). In a sham protocol the effects of 100% oxygen, then those of 50 and 75% nitrous oxide, were studied while the rabbit remained conscious.

4. In unanaesthetized rabbits, in the presence or absence of nitrous oxide, the normal biphasic haemodynamic response to simulated haemorrhage occurred. The first, vasoconstrictor, phase was attenuated by halothane, ketamine and propofol, so that arterial pressure fell more steeply than normal. Not only was the vasoconstrictor phase unaffected by alfentanil but it was extended, so that arterial pressure remained at a normal level even when cardiac output had fallen by 59%. This effect of alfentanil appeared to be mediated centrally, since it could be reproduced by injecting small doses (1.5–7.5 μg) into the fourth ventricle. All four anaesthetic agents and nitrous oxide attenuated the baroreceptor control of heart rate. The effect was least with nitrous oxide and alfentanil, greatest with halothane.
LACK OF EFFECT OF GRANULOCYTE‐MACROPHAGE COLONY STIMULATING FACTOR ON THE RAT AORTA OR HUMAN SAPHENOUS VEIN
Authors: Watabe T. , Moulds R. F. W.
Published: June 2007

1. In order to assess whether the observed hypotensive response in some patients given human granulocyte‐macrophage colony stimulating factor (GM‐CSF) is caused by a direct vascular effect of the GM‐CSF, the effects of mouse and human GM‐CSF were examined in rat aortic rings and human saphenous veins respectively.

2. No effects of GM‐CSF were observed, either in the presence or absence of endothelium, on responses to the α‐adrenoceptor agonist phenylephrine.

3. These data suggest that GM‐CSF does not have direct effects on either vascular endothelium or smooth muscle, and that a direct vascular effect of GM‐CSF is not the explanation for the observed clinical response.
THE EFFECT OF PRAZOSIN THERAPY ON PLATELET ACTIVATION IN ESSENTIAL HYPERTENSION
Authors: Okrucká A. , Pechán J. , Mikulecký M.
Published: June 2007

1. Plasma levels of β‐thromboglobulin, initial and total platelet aggregation (induced by adrenaline or adenosine diphosphate [ADP]) were determined in 26 normotensive subjects and 26 patients with untreated essential hypertension. Groups of 18 essential hypertensive patients and 18 age‐ and sex‐matched normotensives were compared.

2. After 7 days of treatment with prazosin in a dose of 2–8 mg daily the above measures were repeated in 18 essential hypertensive patients. A significant increase in plasma levels of β‐thromboglobulin, initial and total adrenaline‐induced as well as ADP‐induced platelet aggregation was found in hypertensives. Prazosin restored the mean arterial blood pressure in hypertensives to normal, but it had no significant influence either on increased β‐thromboglobulin levels or on initial and total aggregability.

3. The results confirm increased platelet aggregation and in vivo platelet activation in patients with essential hypertension; however there is a discrepancy with previous reports about those results obtained after prazosin therapy. The results suggest that increased platelet aggregation and in vivo activation need not be restored to normal after effective antihypertensive therapy alone. They give reason for the combination of antihypertensive together with anti‐aggregatory therapy in essential hypertension.
SODIUM INTAKE MODULATES RENAL VASCULAR REACTIVITY TO ENDOTHELIN‐1 IN DAHL RATS
Authors: Grossman Ehud , Hoffman Aaron , Keiser Harry R.
Published: June 2007

1. The systemic and renal haemodynamic responses to endothelin‐1 (ET1) were evaluated and compared to Angiotensin II (AII) in anaesthetized Dahl salt‐sensitive (DS) and salt‐resistant (DR) rats on either low (0.1% NaCl in diet) or high (8% NaCl in diet) salt intake.

2. Baseline mean arterial pressure on low salt diet was similar in both strains, while on high salt diet it was 73 ± 4 mmHg in DR rats and 119 ± 8 mmHg in DS rats (P<0.05). Baseline renal blood flow (RBF) and renal vascular resistance (RVR) were similar in all groups.

3. AII in bolus injection induced a short, dose‐dependent increase in blood pressure and renal vascular resistance and a fall in renal blood flow. The maximal pressure increase was significantly greater in DS rats on high salt diet than that in each of the other groups (P<0.05). The fall in renal blood flow and the increase in renal vascular resistance were attenuated in both strains on low salt diet.

4. ET1 induced an initial decrease followed by a prolonged increase in blood pressure; both phases were similar in all groups. However, renal vascular reactivity to ET1 was markedly modulated by salt intake. On low salt diet, following a bolus injection of ET1 (1 nmol/kg), RBF decreased by 34% in DR and by 20% in DS rats, while on high salt diet RBF decreased by 34% in DR and by 80% in DS rats (P<0.05 high vs low salt). RVR increased only by 98% and 72% on low salt diet in DR and DS rats, respectively (P<0.05 vs baseline), whereas on high salt diet RVR increased by 584% and 554% in DR and DS rats respectively (P<0.05 high vs low salt).

5. It is concluded that DS rats are not hypersensitive to ET1 as they are to other pressor agents, and that salt intake, rather than blood pressure, modulates substantially the renal vascular reactivity to ET1.
SELECTIVE DEPRESSION OF MAXIMUM RATE OF DEPOLARIZATION OF GUINEA‐PIG VENTRICULAR ACTION POTENTIALS BY AMIODARONE AND LIGNOCAINE IN SIMULATED ISCHAEMIA: COMPARISON WITH ENCAINIDE
Authors: Campbell Terence J. , Hemsworth Paul D.
Published: June 2007

1. Standard microelectrode techniques were used to record intracellular action potentials from guinea‐pig ventricular myocardium superfused with either control physiological saline (pH 7.5; pO2 500 mmHg; [K+] 5.6 mmol/L) or ‘simulated ischaemic’ solution (pH 6.4; pO2 90 mmHg; [K+] 11.2 mmol/L).

2. The effects on action potential parameters of therapeutic concentrations of lignocaine, amiodarone and encainide were studied under both conditions.

3. Simulated ischaemia, in the absence of drugs, produced marked reductions in resting potential (‐ 86.6 ± 2.3 to ‐ 64.7 ± 3.5 mV), maximum rate of depolarization (V̇max; 263 ± 66 to 106 ± 36 V/s) and action potential duration (164 ± 24 to 97 ± 26 ms). No drug produced any additional effect on resting potential.

4. All three drugs produced enhanced depression of Vmax in ischaemia compared to control conditions (class I effect). This was much more marked for lignocaine and amiodarone (inactivated channel blockers) than for encainide (open channel blocker).

5. In addition the prolongation of action potential duration seen with acute exposure to amiodarone (174 ± 12 to 192 ± 17 ms; class III effect) was abolished under simulated ischaemic conditions.

6. It is concluded that lignocaine and amiodarone exert greater selectivity for ischaemic tissue than does encainide and that amiodarone may function primarily as a class I agent under ischaemic conditions.
EFFECTS OF ENDOTHELIAL CELL REMOVAL ON α‐ADRENOCEPTOR‐MEDIATED RESPONSES OF AORTAE OF PREGNANT RATS
Authors: Jansakul C. , King R. G. , Boura A. L. A.
Published: June 2007

1. The possibility that changes in sensitivity of the aorta occurring during pregnancy in the rat are due to changes in uptake mechanisms, α‐ and/or β‐adrenoceptor‐mediated responses was investigated.

2. Thoracic aortic rings from 20 day pregnant rats showed increased sensitivity to the constrictor effects of phenylephrine, with increased maximum responses when compared with those from non‐pregnant animals. Removal of endothelium caused leftward shifts of the log concentration‐response curves with further increases in maxima to the same extent in rings of both non‐pregnant and 20 day pregnant rats.

3. Propranolol, β‐oestradiol, and nisoxetine did not significantly alter the CR‐curves to phenylephrine of endothelium‐intact or denuded thoracic aortic rings obtained from either non‐pregnant or 20 day pregnant rats.

4. BHT‐920 failed to cause marked constriction of endothelium‐intact rings. After removal of endothelium, significant constrictor responses to BHT‐920 occurred which were of similar magnitude for rings from both non‐pregnant and 20 day pregnant rats.

5. Relaxant responses to BHT‐920 of endothelium‐intact rings preconstricted with phenylephrine were not significantly different between those from non‐pregnant and 20 day pregnant rats. Removal of endothelium resulted in rightward shifts of the curves together with decreased maximum responses.

6. These results support earlier suggestions that the endothelium plays a role in controlling vascular reactivity to phenylephrine. The increased maximum response of thoracic aortic rings to phenylephrine seen during pregnancy does not appear to be due to marked changes in amine uptake mechanisms or β‐ or α2‐adrenoceptor‐mediated responses.
SUPPRESSOR CALCIUM INFUSION RAISES PLASMA ATRIAL NATRIURETIC PEPTIDE CONCENTRATIONS IN HUMANS
Authors: Finn Wendy L. , Tunny Terry J. , Klemm Shelley A. , Thompson Robyn E. , Gordon Richard D.
Published: June 2007

1. Calcium was infused in normal subjects in subpressor dosage to examine the effects of raised calcium levels on atrial natriuretic peptide (ANP) concentrations.

2. Calcium infusion progressively raised serum ionized and total calcium concentrations significantly, without raising mean arterial pressure or heart rate.

3. Plasma ANP concentrations increased significantly by 5 min of infusion and increased further by 15 min (approximately 40%) to levels which were maintained to 60 min.

4. Urinary sodium excretion increased by 140% during calcium infusion.

5. Calcium may affect secretory as well as contractile functions of the atrial myocyte.
BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN‐ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY
Authors: Klemm Shelley A. , Gordon Richard D. , Tunny Terry J. , Finn Wendy L.
Published: June 2007

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets.

2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction.

3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure.

4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet.

5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.
VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS
Authors: Langton David , Way Diana , Trigg Lisbeth , Blake Duncan , McGrath Barry
Published: June 2007

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve.

2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF.

3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed.

4. Renal sympathectomy ablated these changes in RBF during exercise.

5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.
HYPERLIPIDAEMIA INCREASES ALBUMINURIA IN HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Cooper M. E. , Vranes D. A. , Panagiotopoulos S. , Allen T. J. , Goodall I. , Jerums G.
Published: June 2007

1. The effects of a high cholesterol diet on urinary albumin excretion were examined in spontaneously hypertensive (SHR) and Wistar‐Kyoto (WKY) rats over 36 weeks.

2. Cholesterol feeding resulted in an increase in total‐cholesterol and a decrease in HDL‐cholesterol without influencing triglyceride levels in both strains.

3. Urinary albumin excretion was significantly elevated in cholesterol‐fed SHR and WKY rats.

4. These results suggest that hyperlipidaemia may be important in acceleration of experimental nephropathy.
EFFECT OF FISH OIL FEEDING ON BLOOD PRESSURE AND VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yin K. , Chu Z. M. , Beilin L. J.
Published: June 2007

1. To examine possible antihypertensive mechanisms of fish oil feeding, we have studied vascular reactivity of aortic rings and blood pressure of spontaneously hypertensive rats (SHR).

2. SHR were fed a synthetic diet supplemented with either (10% by weight) ‘Max EPA’ fish oil or hydrogenated coconut oil (saturated fat) for 4 weeks.

3. Mean systolic blood pressure of fish oil fed rats was 9 mmHg lower than saturated fat fed controls.

4. Aortic rings of control SHR had a biphasic response to acetylcholine (ACh), relaxing at lower concentrations but contracting at concentrations higher than 3X10‐7 mol/L. No such contractions were seen in tissues of fish oil fed rats. The contractions were abolished by indomethacin, suggesting that they were caused by a cyclo‐oxygenase product.

5. Tissue analysis showed that both aortic and serum generation of thromboxane B2 (TxB2) was approximately three times less in fish oil fed rats than in control tissues.

6. These results indicate that the lowering of blood pressure in fish oil fed SHR could in part be due to decrease in production of thromboxane (TxA2), a potent vasoconstrictor, hence influencing vascular tone and compliance of the aorta.
MECHANISMS OF THE EFFECTS OF ENDOTHELIN ON RESPONSES TO NORADRENALINE AND SYMPATHETIC NERVE STIMULATION
Authors: Wong‐Dusting H. K. , La M. , Rand M. J.
Published: June 2007

1. The effects of endothelin (0.1–1 nmol/L) and the phorbol ester, phorbol 12‐myristate 13‐acetate (PMA, 0.1–100 nmol/L) have been studied on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline in the rabbit isolated ear artery.

2. Endothelin (0.1 nmol/L) significantly enhanced the biphasic response of the arteries to a prolonged period of sympathetic nerve stimulation (2 Hz for 60 s). Both the component of the response attributable to mobilization of intracellular calcium (phasic response) and the component due to the influx of extracellular calcium (tonic response) were enhanced.

3. PMA (0.1 and 0.3 nmol/L), which activates protein kinase C, enhanced vasoconstrictor responses to noradrenaline but a higher concentration of PMA (100 nmol/L) inhibited responses to noradrenaline.

4. It is concluded that the enhancement of responses to sympathetic nerve stimulation and noradrenaline produced by endothelin may be due to facilitation of the influx of extracellular calcium and to the activation of protein kinase C.
REDUCED V1 VASOPRESSIN BINDING IN THE RAT NUCLEUS SOLITARII AFTER NODOSE GANGLIONECTOMY
Authors: Phillips P. A. , Widdop R. E. , Chai S‐Y. , Kelly J. , Mooser V. , Trinder D. , Johnston C. I.
Published: June 2007

1. Anaesthetized male Sprague‐Dawley rats underwent unilateral nodose ganglionectomy or sham operation.

2. One week later hindbrain V1 vasopressin binding site density was assessed by in vitro autoradiography with the selective V1 antagonist radiolgand [125I] [d(CH2)5, Sar7]AVP.

3. Specific binding was observed in the nodose ganglion, nucleus tractus solitarius (NTS), area postrema, and inferior olive. Only binding in the medial subnucleus of the NTS was reduced by ipsilateral nodose ganglionectomy.

4. These findings are consistent with V1 vasopressin receptors occurring pre‐synaptically on vagal primary viscerosensory afferent fibres.

5. Such receptors may be involved in the effect of AVP on blood pressure and/or the baroreflex.
HAEMODYNAMIC EFFECT OF ENDOTHELIN, A NOVEL POTENT VASOCONSTRICTOR IN DOGS
Authors: Otsuka Atsuhiro , Mikami Hiroshi , Katahira Katsutoshi , Tsunetoshi Takeshi , Kohara Katsuhiko , Minamitani Kaori , Moriguchi Atsushi , Ogihara Toshio
Published: June 2007

1. The effects of endothelin (40 and 400 pmol/kg, intravenous (i.v.), a novel vasoconstrictor, on haemodynamics were evaluated in normal dogs and dogs treated with hexamethonium.

2. The lower dose of endothelin caused no significant changes in mean blood pressure (MBP), heart rate (HR), cardiac output (CO), or total peripheral resistance (TPR) in normal dogs. In dogs treated with hexamethonium MBP decreased transiently associated with decrease in TPR.

3. In both dogs, the higher dose of endothelin caused MBP increase with CO increase in an early phase, and with TPR increase in a later phase. In normal dogs, the CO decreased 60 min after endothelin, but in dogs treated with hexamethonium the decrease in CO was not significant.

4. Electrocardiograms showed ST changes and arrhythmias.

5. Thus, endothelin has dual effects on both the vasculature and the heart, its effect depending on its dose and the time after its administration: initial vasodilation followed by prolonged vasoconstriction, and cardiostimulation followed by cardiosuppression. The cardiosuppression appears to be mediated in part by a neural mechanism.