bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADRENAL TRANSITIONAL ZONE STEROIDS, 18‐OXO AND 18‐HYDROXYCORTISOL, USEFUL IN THE DIAGNOSIS OF PRIMARY ALDOSTERONISM, ARE ACTH‐DEPENDENT
Authors: Hamlet Stephen M. , Gordon Richard D. , Gomez‐Sanchez Celso E. , Tunny Terry J. , Klemm Shelley A. 
Published: June 2007

SUMMARY1. The adrenal cortical ‘hybrid’ steroids 18‐oxocortisol (18‐OF) and 18‐hydroxy‐cortisol (18‐OHF) are elevated in patients with typical angiotensin‐unresponsive aldosterone‐producing adenoma (AII‐unresponsive APA) and fall to normal following surgical removal of the adrenal containing the tumour. Since 18‐OF was six times the upper limit of normal pre‐operatively, the tumour was the site of overproduction of hybrid steroids.2. The failure of angiotensin‐responsive APA to overproduce the hybrid steroids may be linked to their more ‘normal’ production of cortisol, which falls significantly on removal of the tumours.3. Hybrid steroid levels were also normal in patients with idiopathic hyperplasia of the adrenals (IHA) and in low renin essential hypertension.4. In All‐responsive APA, glucocorticoid‐suppressible hyperaldosteronism (GSH) and IHA, the hybrid steroids showed brisk responses to stimulation by ACTH and suppression by dexamethasone of endogenous ACTH.5. Long‐term suppression by dexamethasone of hybrid steroids in GSH is consistent with ACTH dependence, rather than angiotensin dependence.6. Studies of the regulation of hybrid steroid secretion in various categories of hypertension will further define the biosynthetic distinctiveness which is already useful diagnostically.
THREE Alu REPEATED SEQUENCES ASSOCIATED WITH A HUMAN GLANDULAR KALLIKREIN GENE
Authors: Schedlich Lynette J. , Morris Brian J. 
Published: June 2007

SUMMARY1. Recently the complete primary structure of a human glandular kallikrein gene, hGK‐1, was reported. The present paper presents further structural information.2. Associated with the gene were three Alu repeated sequences: one in the second intron and two approximately 0.4 kb and 1.2 kb upstream.3. The 5′ non‐coding and 5′ flanking DNA was highly homologous to that in the mouse genes.4. Different polyadenylation signals are used in different human kallikrein genes.
HIGH SALT DIET DECREASES LONGEVITY IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Di Nicolantonio R. , Silvapulle M. J. , Spargo S. , Morgan T. O. 
Published: June 2007

SUMMARY1. Blood pressure, body weight and mortality rate were examined in female spontaneously hypertensive rats (SHR) of the Okamoto strain maintained on a lifelong high (5% NaCl w/w) or low (0.1% NaCl w/w) salt diet.2. A high salt diet increased mortality and decreased body weight in SHR, but failed to significantly alter blood pressure up to 24 months of age.3. Hence, a low salt diet does not appear to be a long‐term risk factor and may protect the SHR from cardiovascular accidents.
THE EFFECT OF DIETARY FISH OIL AND LONG‐TERM SALT LOADING ON BLOOD PRESSURE AND EICOSANOID METABOLISM IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Croft K. D. , Beilin L. J. , Codde J. , Vandongen R. 
Published: June 2007

SUMMARY1. Dietary suppression of prostanoid synthesis with fish oils has had little effect on blood pressure in models of experimental hypertension in rats. However, a pressor effect of dietary fish oils was observed in spontaneously hypertensive rats (SHR) subject to 1 week of salt loading.2. Animals were allocated to semisynthetic diets containing either 10% by weight Max EPA fish oil or a control diet of coconut oil, and studied after receiving 1.5% saline for 4 weeks.3. Within the first week of salt loading, SHR‐fed fish oil showed an increase in blood pressure (mean = 9 mmHg) relative to controls. This effect was transient, and after the first week of salt loading there was little difference in blood pressure between the two dietary groups.4. Following dietary treatment there were substantial changes in plasma fatty acid composition with a 48% decrease in arachidonic acid content of fish oil‐fed rats compared with control animals. Rats on the fish oil diet showed a threefold decrease in serum thromboxane generation. Prostacyclin production by incubated segments of aorta was reduced by more than 50% compared with the coconut oil‐fed control group.5. SHR on the fish oil diet showed increased urine volume and sodium excretion, presumably due to increased fluid and salt intake.6. This study shows that dietary suppression of prostacyclin synthesis is associated with only a minor effect on blood pressure in long‐term salt loading of SHR.
AN ANALYSIS OF THE HAEMODYNAMIC EFFECTS OF TOLBUTAMIDE IN CONSCIOUS DOGS
Authors: Lee King C. , Wilson Randall A. , Randall David C. , Altiere Ralph J. , Kiritsy‐Roy Judith A. 
Published: June 2007

SUMMARY1. In conscious chronically instrumented dogs, tolbutamide (5–45 mg/kg) induced significant dose‐related increases in mean arterial pressure and left ventricular enddiastolic pressure.2. Cardiac output was descreased while heart rate, d(LVP)/dt, and regional myocardial performance at the left ventricle were not significantly affected. Computed total peripheral resistance was increased.3. Pretreatment with the a‐antagonist phentolamine (1–1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 μg/kg) was enhanced by pretreatment with tolbutamide (45 mg/kg).4. In an isolated tissue preparation using ring segments of canine femoral arteries, neither tolbutamide nor its major hepatic metabolites (carboxytolbutamide, p‐toluenesulfonamide and p‐toluenesulfonylurea) caused any smooth muscle contraction. However, pretreatment of these tissues with 10–4, 10–3, or 10–2 mol/l tolbutamide potentiated the contractile response to norepinephrine by up to 19% and to phenylephrine by up to 8%.5. It was concluded that the pressor effect of tolbutamide arises by potentiating the a‐adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines.
DIHYDROCYCLOSPORIN D IN SHEEP: HAEMODYNAMIC AND RENAL EFFECTS
Authors: Tresham J. J. , Whitworth J. A. , de Lima J. J. G. , McDougall J. G. , Scoggins B. A. 
Published: June 2007

b1. This study was designed to test the haemodynamic and renal effects in sheep of dihydrocyclosporin D (dCyD), an immunosuppressant agent derived from the fungus Tolypocladium inflatum Gams.2. dCyD was infused for 5 days at 12 mg/kg per day. Mean arterial pressure (MAP) was elevated after 24 h, but thereafter returned to control levels. Heart rate was significantly elevated throughout the infusion and was still high 24 h postinfusion. Cardiac output rose after 5 days, but total peripheral resistance was unchanged during the infusion.3. Glomerular filtration rate, renal blood flow and effective renal plasma flow remained unchanged, although urine sodium excretion rose for the first 48 h.4. Infusion of the castor oil‐based vehicle for cyclosporin, Cremaphore EL, for 5 days in four sheep did not produce any sustained changes in any of the parameters measured.
THE EFFECT OF TRIFLUOPERAZINE ON BRONCHIAL RESPONSIVENESS IN ASTHMA
Authors: Bowden J. J. , Latimer K. M. , Crockett A. J. , Ruffin R. E. 
Published: June 2007

SUMMARY1. The protective effects of oral trifluoperazine (TFP) (7mg) against standardized methacholine and histamine inhalation tests (MIT and HIT) were examined 2 and 22 h post‐treatment in eight stable asthmatics using a randomized double‐blind protocol.2. A preliminary study tested whether a preceding MIT influenced the result of a subsequent HIT.3. The mean baseline forced expiratory volumes in 1 s (FEV1) were similar prior to placebo and TFP. The mean FEV1 values 2 h after ingestion of placebo or TFP were not different from the baseline values.4. TFP did not alter bronchial responsiveness to inhaled methacholine or histamine 2 h postingestion, but at 22 h the PC20 methacholine was greater than placebo, while PC20 histamine did not change. This change in methacholine responsiveness was not clinically significant.5. There was a correlation between geometric mean provocative concentration of histamine to cause 20% fall in FEV (PC20H) for HIT performed in isolation ('separate day') and for HIT performed after MIT (‘same day’).6. The effect of inhaled TFP (10 mg/ml, nebulized for 5 min) was examined single‐blind and placebo‐controlled in a separate group of six stable asthmatics.7. Inhaled TFP had a bronchoconstrictor effect in all six asthmatics. The mean fall in FEV1 was 36.4% after inhaled TFP and 2.1% after saline.8. In the asthmatics studied, ingested TFP exhibited a weak anticholinergic effect 22 h pest‐treatment, but a brisk spontaneously self reverting bronchoconstrictor response was invariably seen when TFP was inhaled.
CALMODULIN‐ANTAGONIST DRUGS AND PORCINE MALIGNANT HYPERPYREXIA
Authors: Collins S. P. , White M. D. , Denborough M. A. 
Published: June 2007

SUMMARY1. Landrace swine were identified as malignant hyperpyrexia susceptible (MHS) or control by the contracture responses of gracilis muscle fibre bundles to 3% halothane, 2 mmol/l caffeine and 80 mmol/l KCI. The effects of calmodulin‐antagonist drugs on the contractile behaviour of control and MHS preparations were investigated in vitro.2. Calmodulin‐antagonists at micromolar concentrations induced contracture in both control and MHS muscle. Pretreatment of MHS muscle with calmodulin‐antagonist drugs potentiated its response to halothane and caffeine.3. These results suggest that calmodulin‐antagonist drugs cause an increase in myoplasmic Ca2+ concentration in both control and MHS muscle.
CARDIOVASCULAR RESPONSE TO EMOTIONAL STRESS AND SPONTANEOUS BLOOD PRESSURE VARIABILITY IN GENETICALLY HYPERTENSIVE RATS OF THE LYON STRAIN
Authors: Julien C. , Cerutti C. , Kandza P. , Barres C. , Su D. , Vincent M. , Sassard J. 
Published: June 2007

SUMMARY1. Intra‐aortic blood pressure (BP) was continuously recorded in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of the Lyon strains under basal conditions and during aversive stimulation (a jet of air for 20 min). Rats were studied when 5 and 14 weeks old.2. The 24 h standard deviation (i.e., variability) of diastolic BP was significantly greater in LH rats of both ages than in LN and LL control rats.3. In response to the stressor, LH rats showed larger increases in BP than age‐matched controls.4. The BP variability was related to the BP responses to stress in the whole series of rats.5. It is concluded that the spontaneous BP variability and the BP responses to an experimental stressor rely upon a common regulatory mechanism in rats and that an increased lability of diastolic BP is a primary characteristic of Lyon hypertensive rats.
CALMODULIN‐INDEPENDENT STIMULATION OF RENIN RELEASE BY EXPOSURE OF RAT KIDNEY CORTICAL SLICES TO CALCIUM
Authors: Matsumura Y. , Koyama Y. , Shinyama H. , Uriu T. , Ichihara T. , Morimoto S. 
Published: June 2007

SUMMARY1. Effects of calcium‐interacting agents on the calcium‐induced stimulation of renin release from kidney cortical slices pretreated with calcium‐free medium were examined.2. The exposure of calcium to the slices pretreated with calcium‐free medium enhanced the release of renin, followed by a decreased response in the release. The amount of lactate dehydrogenase released from the slices did not correlate with that of renin.3. High potassium depolarization significantly potentiated the decreased response of renin release, with no influence on the stimulation of the release by exposure to calcium.4. The decrease in renin release was attenuated by calcium‐interacting agents, such as nifedipine, TMB‐8 and W‐7, but these agents were without effect on the stimulation of the release by exposure to calcium.5. Thus, the calcium‐calmodulin system apparently is not involved in the increased response of renin release following exposure to calcium.
COMPARISON OF THE ACTIVITY OF CIRCULAR AND LONGITUDINAL MYOMETRIUM FROM PREGNANT RATS: CO‐ORDINATION BETWEEN MUSCLE LAYERS
Authors: Tomiyasu B. A. , Chen C. J. , Marshall J. M. 
Published: June 2007

SUMMARY1. Contractions and electrical activity were recorded from isolated segments of longitudinal (L) and circular (C) myometrium from rats on gestation days 16–17 and 21 before and during parturition.2. The segments were arranged so that the activity of the two layers could be monitored simultaneously and independently.3. Out of the 15 preparations from days 16–17, 13 showed no co‐ordination of activity between the layers. In the other two preparations a large contraction of C occasionally initiated a contraction of L. Surgical separation of the layers disrupted the co‐ordination and L then developed its independent rhythm.4. On day 21 before delivery, eight of 10 preparations exhibited 1:1 co‐ordination of activity between the two layers, but C did not consistently pace L. The pacing shifted from one layer to the other several times during an experiment.5. During parturition there was a 1:1 co‐ordination of activity in all 10 preparations examined. In nine of these L initiated the activity of the C. Surgical separation of the layers disrupted the co‐ordination and C developed its independent rhythm. In one the pacing shifted from one layer to the other several times during the experiment.6. In all cases where co‐ordination between the layers was observed it was myogenic and apparently related to the spread of action potentials between the two muscles.
ARRHYTHMOGENIC EFFECT OF FORSKOLIN IN THE ISOLATED PERFUSED RAT HEART: INFLUENCE OF NIFEDIPINE REDUCTION OF EXTERNAL CALCIUM
Authors: Huang X. D. , Wong T. M. 
Published: June 2007

SUMMARY1. This study investigated first the effects of forskolin on cardiac rhythm, and second the roles of calcium in cardiac arrhythmogenesis by cAMP.2. Two series of experiments were performed. In the first series, forskolin was administered into the isolated perfused rat heart. In the second series, forskolin administration was preceded by administration of nifedipine, a calcium channel blocker, or infusion of a low concentration calcium solution. In both experiments, the myocardial cAMP level and electrocardiogram were determined.3. It was found that forskolin increased cAMP level as well as inducing arrhythmia. Pretreatment with nifedipine or a reduction of external calcium, that either maintained or further enhancd the forskolin‐induced increase in the cAMP level, abolished the forskolin‐induced arrhythmia.4. The results of the present study support the hypothesis that myocardial cAMP mediates cardiac arrhythmia, and provide evidence that calcium is essential in arrhythmia mediated by cAMP.
ADRENOCORTICAL STEROID REQUIREMENTS FOR INITIATION OF ACTH‐DEPENDENT HYPERTENSION IN SHEEP
Authors: Spence Campbell D. , Coghlan John P. , Denton Derek A. , Mills Eric H. , Whitworth Judith A. , Scoggins Bruce A. 
Published: June 2007

SUMMARY1. Previous studies demonstrated that the combined infusion of cortisol (F), aldosterone (ALDO), deoxycorticosterone (DOC), corticosterone (B), 11‐deoxycortisol (S), 17α‐hydroxyprogesterone (17αOHP) and 17α, 20α‐dihydroxy‐4‐pregnane‐3‐one (17α20αOHP), at rates equivalent to their production during adrenocorticotrophic hormone (ACTH) treatment, reproduced the pressor and metabolic responses to ACTH administration in sheep.2. This study examined which of these adrenocortical steroids were necessary for the initiation of the hypertension produced by these steroids in sheep.3. Infusion of F, ALDO, 17αOHP and 17α20αOHP together, increased MAP by 19 mmHg, similar to both complete steroid cocktail (+25 mmHg) or ACTH administration (+ 21 mmHg). Infusion of F, 17αOHP and 17α20αOHP increased MAP by +7 mmHg. Infusion of ALDO, 17αOHP and 17α20αOHP had no effect on MAP. Thus F and ALDO were essential for the pressor effects of the steroid infusion.4. To determine the role of glucocorticoid activity in the MAP rise, prednisolone, a non‐pressor glucocorticoid, was substituted for cortisol. Combined prednisolone, ALDO, 17αOHP and 17α20αOHP infusion did not raise blood pressure. This suggested that the mineralocorticoid component rather than glucocorticoid component of cortisol's activity was involved in the pressor response.5. Aldosterone (7 μg/h) was substituted for cortisol, giving a total of 10 μg/h aldosterone. High dose ALDO (10 μg/h), 17αOHP and 17α20αOHP infusion raised blood pressure by 18 mmHg. Thus, the essential role of cortisol appeared to be due to its occupancy of mineralocorticoid receptors, rather than glucocorticoid receptors.6. Given that ACTH produces a transient initial increase in aldosterone secretion of up to 10 μg/h, it appears that aldosterone and not cortisol is essential for the pressor effects of ACTH.7. Hypertension resulting from the combined steroid infusion in the sheep appears to be produced by a mechanism which involves a complex interaction between ALDO, F, 17αOHP and 17α20αOHP. Therefore, the putative ‘hypertensinogenic’ receptor may be multivalent with binding sites for F, ALDO and 17α20αOHP, or is a site of single interactive receptors for these steroids and that F exerts its permissive action by occupying the same site as ALDO on the hypertensinogenic receptors.
MATERNOFETAL TRANSFER OF PHENYTOIN, p‐HYDROXY‐PHENYTOIN AND p‐HYDROXY‐PHENYTOIN‐GLUCURONIDE IN THE PERFUSED HUMAN PLACENTA
Authors: Dickinson R. G. , Fowler D. W. , Kluck R. M. 
Published: June 2007

SUMMARY1. Transplacental transfer of the anti‐epileptic agent phenytoin (PHT), its phase I metabolite, p‐hydroxy‐phenytoin (p‐OH‐PHT), and its phase II conjugate p‐OH‐PHT‐glucuronide, was studied in term placental lobules perfused single pass in both maternal and fetal circuits.2. Ratios of clearance of PHT, p‐OH‐PHT and p‐OH‐PHT‐glucuronide to clearance of antipyrine were 1.08 ± 0.03, 0.52 ± 0.02 and 0.12 ± 0.01 (mean and s.e.m.), respectively.3. Transfer was positively correlated with lipophilicity as measured by the apparent partition coefficient determined between octanol and pH 7.4 buffer.
INHIBITION OF SYMPATHETIC NEUROTRANSMISSION BY THE OPIOID δ‐RECEPTOR AGONIST DAMA IN THE PITHED RAT
Authors: Wong‐Dusting Helen , Rand Michael J. 
Published: June 2007

SUMMARY1. The effects of [d‐Ala2, Met5]enkephalinamide (DAMA), an analogue of [Met5]‐enkephalin that acts selectively on opioid receptors of the 8‐subtype, were studied on pressor responses elicited by sympathetic stimulation in pithed rats.2. Intravenous injections of bolus doses of 0.1 mg/kg and 0.3 mg/kg of DAMA did not affect either the basal blood pressure or pressor responses to noradrenaline.3. Pressor responses elicited either by electrical stimulation of the spinal sympathetic outflow or by stimulation of sympathetic ganglion cells with the muscarinic agonist McN‐A‐343 were reduced by DAMA.4. Naloxone (1 mg/kg + 0.5 mg/kg per h) had no significant effect on the basal blood pressure or on pressor responses to spinal sympathetic stimulation, but antagonised the inhibitory effect of DAMA.5. These results indicate that activation of opioid 8‐receptors on sympathetic vasomotor nerve terminals can inhibit noradrenergic neurotransmission.
STUDIES ON THE BIPHASIC RELAXANT CURVE OF GLYCERYLTRINITRATE IN RAT AORTA: ROLE OF GTN METABOLITES
Authors: Malta Errol 
Published: June 2007

SUMMARY1. The present study has examined the possibility that one or more metabolites of glyceryltrinitrate (GTN) (i.e. glyceryl‐1,2‐ and ‐1,3‐dinitrate and glyceryl‐1‐ and ‐2‐mononitrate) may be responsible for the second phase of the biphasic relaxant curve to GTN in phenylephrine‐contracted rings of rat aorta.2. The IC50 values for the two phases of the GTN curve were 0.1 μmol/L and 12 μmol/L with the initial phase eliciting 60% of the total relaxation response. The curves for glyceryl‐1,2‐ and ‐1,3‐dinitrate were monophasic with IC50 values of 248 μmol/L and 110 μmol/L, respectively. The mononitrate metabolites elicited relaxant effects at concentrations ≥ 1 mmol/L.3. The induction of tolerance to GTN or pretreatment with oxyhaemoglobin (5 μmol/L) resulted in a monophasic GTN curve with IC50 values of 16 μmol/L and 18 μmol/L respectively suggesting selective abolition of responses to low concentrations of GTN with little effect on responses to high concentrations of GTN. The relaxant effects of the ‐1,2‐ and ‐1,3‐ dinitrates, like that to GTN, were essentially unaltered by GTN tolerance or oxyhaemoglobin.4. Thus while the relaxant effects of the dinitrate metabolites possess similar properties to that of the second phase of relaxation to GTN, a role for these metabolites is unlikely since their IC50 values are 9–20‐fold greater than that for the second phase of relaxation to GTN. Whether these differences are due to the 8–10‐fold lower lipophilicity of the dinitrates as compared with the parent compound requires further study.
SYNERGISTIC POTENTIATION BY CAPTOPRIL AND PROPRANOLOL OF BRADYKININ‐INDUCED BRONCHOCONSTRICTION IN THE GUINEA‐PIG
Authors: Lau W. A. K. , Rechtman M. P. , Boura A. L. A. , King R. G. 
Published: June 2007

SUMMARY1. Captopril (30 or 100 μg/kg intravenous (i.v.)) in anaesthetized artificially ventilated guinea‐pigs potentiated bronchoconstrictor responses to bradykinin, but not those to histamine or the thromboxane A2‐mimetic U46619.2. Propranolol (5 mg/kg, i.v.) potentiated bradykinin‐induced bronchoconstriction. The potentiated responses were further augmented by captopril.3. The captopril‐potentiated responses to bradykinin were inhibited during cyclo‐oxygenase inhibition with indomethacin. Bronchoconstrictor responses to bradykinin, but not those to histamine or U46619, were reduced after thromboxane synthase inhibition with dazoxiben. The thromboxane A2 antagonist AH23848 inhibited bronchoconstrictor responses to bradykinin, arachidonic acid or U46619 whereas it did not affect those to histamine.4. A kininase I inhibitor dl‐2‐mercaptomethyl‐3‐guanidinoethyl thiopropanoic acid caused no change in bronchoconstriction caused by bradykinin and did not alter the potentiated responses occurring after captopril.5. Thus, confirmation has been obtained that bradykinin causes bronchoconstriction in the guinea‐pig indirectly, by release of eicosanoids. Thromboxane A2 is likely to be the major eicosanoid released, since the bronchoconstrictor effect of bradykinin was blocked by indomethacin, dazoxiben and AH23848. The intensity of the bronchoconstriction appears dependent on sympathetic influences mediated by β‐adrenoceptors. Kininase I, in contrast to kininase II apparently has little role in terminating the effects of bradykinin in the lung.
EFFECTS OF ADENOSINE ANTAGONISM AND β‐BLOCKADE DURING LOW‐FLOW ISCHAEMIA IN RAT HEART
Authors: Headrick J. P. , Willis R. J. 
Published: June 2007

SUMMARY1. The effects of adenosine antagonism (8‐phenyltheophylline) and β‐blockade (1‐propranolol) were examined during low‐flow ischaemia (0.5 mL/min per g for 20 min) in rat heart.2. Myocardial adenosine release, heart rate, and left ventricular developed pressure were monitored to determine whether endogenous adenosine affected ischaemic function directly, and/or via interaction with endogenous catecholamines.3. Adenosine release increased more than 10‐fold during low‐flow ischaemia. Release displayed a phasic pattern, with maximal release occurring at 10 min. Ischaemia produced bradycardia (—180 beats/min) which was reduced by 8‐phenyltheophylline infusion (P < 0.001, n= 10). Adenosine antagonism also significantly increased left ventricular developed pressure in the initial 5 min of ischaemia (P < 0.001, n= 10).4. β‐blockade alone was without effect in ischaemic hearts, however, β‐blockade significantly reduced the initial increases in heart rate and developed pressure observed during infusion of 8‐phenyltheophylline (P < 0.001, n= 10). The effect of β‐blockade was transient, occurring in the initial 5–6 min of ischaemia.5. The data indicate that endogenous adenosine directly mediates > 30% of the bradycardia associated with low‐flow ischaemia, and that endogenous adenosine inhibits the release and/or the effects of endogenous catecholamines produced during the initial 5–6 min of ischaemia.