bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF ANAESTHETICS AND TRAUMA ON STIMULATED GASTRIC ACID SECRETION IN CHRONIC FISTULA DOGS
Authors: Bastaki SMA , Waton NG 
Published: June 2007

SUMMARY1. The present study was undertaken to determine whether various anaesthetic agents affect canine gastric acid secretion independently of other experimental variables.2. Acid secretory output was determined in dogs with chronic fistulae, by administering sedating doses of anaesthetics commonly used for studying gastric secretory mechanisms in laboratory animals.3. The anaesthetic agents inhibited gastric acid secretion. As the inhibitory effect of the mixture of anaesthetics was pronounced, an attempt was made to study the effect of each individual anaesthetic agent separately.4. Acetopromazine was given to sedate dogs. Although it has a long duration of action, it only had a transient inhibitory action on gastric acid secretion of 15–30 min duration. Moreover the drug reduced pentagastrin‐stimulated secretion, but had no effect on histamine‐stimulated secretion.5. Thiopentone sodium given with acetopromazine produced a mild inhibitory effect on histamine‐stimulated secretion for 45 min, but produced a more pronounced and sustained inhibitory effect on pentagastrin‐stimulated secretion.6. Trilene significantly inhibited both histamine‐ and pentagastrin‐stimulated secretion. The effect on the latter was more pronounced and sustained.7. Trauma had no significant effect on histamine‐stimulated secretion, but showed a slight inhibitory effect on pentagastrin‐stimulated secretion.8. Experiments to study gastric secretory mechanisms and antisecretory drugs should take account of the potential inhibitory effects of anaesthetics. Where possible, studies in conscious dogs with gastric fistulae are preferable to experiments on anaesthetized animals.
ANGIOTENSIN CONVERTING ENZYME INHIBITION IN THE POSTNATAL RAT RESULTS IN DECREASED CELL PROLIFERATION IN THE RENAL OUTER MEDULLA
Authors: McCausland Jane E , Ryan Graeme B , Alcorn Daine 
Published: June 2007

SUMMARY1. Chronic angiotensin converting enzyme (ACE) inhibition or AT1 antagonism during postnatal development in the rat has been shown to cause renal tubular and vascular damage, particularly in the outer medulla.2. The effects of ACE inhibition were investigated at a stage of development before the renal outer medulla is fully established.3. Sprague‐Dawley rat pups were given daily i.p. injections of either enalapril or saline from days 3–10. At day 11, kidneys were perfusion‐fixed for either electron microscopy or immunocytochemistry. Sections were incubated in proliferating cell nuclear antigen (PCNA) antisera and the avidin‐biotin immunoperoxidase method was used to detect an immunoreactive product, indicative of proliferating cells.4. Following enalapril treatment, the normal structural arrangement of the outer medulla was disrupted compared with controls. Cell proliferation (PCNA‐positive cells) in the medullary rays was reduced in enalapril‐treated kidneys compared with control kidneys.5. Thus, angiotensin II appears to be essential for normal tubular and vascular growth in postnatal renal development in the rat.
EFFECTS OF ANTIHYPERTENSIVE DRUGS ON CORONARY ARTERY DISEASE RISK: A META‐ANALYSIS
Authors: Howes LG , Lykos D. , Rennie GC 
Published: June 2007

SUMMARY1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical significance of these effects and the extent to which they persist during long‐term therapy is uncertain.2. We performed a meta‐analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a β‐blocker with β2‐adrenoceptor intrinsic sympathomimetic activity), enalapril, nifedipine and doxazosin on plasma cholesterol, low density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C), triglycerides and blood pressure (BP).3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations.4. While there were no differences in antihypertensive efficacy between the drugs, atenolol significantly (P > 0.05) reduced HDL‐C and increased total cholesterol, LDL‐C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine.5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 years for celiprolol).6. The improvement in Framingham equation point scores (systolic BP formula) was significantly (P > 0.05) less for atenolol (− 0.54; confidence intervals (CI) − 0.29–0.78) than for celiprolol (−1.69; CI −0.68 ‐2.70), doxazosin (−1.67; CI −1.11–2.23), enalapril (−1.43; CI 0.23–3.07) and nifedipine (−1.91; CI −1.22–2.59). Similar results were obtained for the Framingham diastolic BP formula.7. These results suggest that the adverse effects of atenolol on plasma lipids do not improve with prolonged therapy and are theoretically great enough to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect plasma lipids. However it must be emphasized that these are theoretical effects. In order to determine the actual differences between these drugs on CAD end points, studies using these end points are required.
PCR‐SSCP ANALYSIS OF THE PROMOTER REGION OF THE RENIN GENE IN PATIENTS WITH ALDOSTERONE‐PRODUCING ADENOMAS
Authors: Ballantine DM , Klemm SA , Tunny TJ , Stowasser M. , Gordon RD 
Published: June 2007

SUMMARYAldosterone‐producing adenomas (APA) of the adrenal gland may be responsive or un‐responsive to the renin‐angiotensin system.2. We have described increased expression of renin mRNA in angiotensin‐responsive aldosterone‐producing adenomas (AII‐R‐APA) compared with angiotensin‐un‐responsive aldosterone‐producing adenomas (AII‐U‐APA) and significantly different allelic frequencies of the BglI, TaqI and HinfI restriction fragment length polymorphisms of the renin gene between the two groups.3. An area including the 5’ flanking region—500 bp from exon 1, exon 1 and intron A contained no gross insertions or deletions when studied by a long polymerase chain reaction technique.4. In the present study, polymerase chain reaction‐single strand conformation polymorphism analysis (PCR‐SSCP) revealed no single base pair alteration in the proximal promoter region (—600 bp to transcription start) of the renin gene in patients with APA (either AII‐U‐APA or AII‐R‐APA) when compared with normal subjects.5. Therefore, mutations in this regulatory region do not appear to explain the different levels of renin gene expression observed in these two subtypes of APA.
GENETIC VARIANTS OF PROTEINS FROM THE RENIN ANGIOTENSIN SYSTEM ARE ASSOCIATED WITH PRESSURE LOAD CARDIAC HYPERTROPHY
Authors: Wong KK , Summers KM , Burstow DJ , West MJ 
Published: June 2007

SUMMARY1. The relationship between the angiotensinogen (AGT) T174M, angiotensin converting enzyme (ACE) insertion/deletion (I/D) and the angiotensin II type 1 receptor (AT1) genetic markers and left ventricular hypertrophy was examined in normal subjects and those with aortic stenosis.2. Subjects with aortic stenosis had higher left ventricular systolic pressure and relative wall thickness (RWT) compared with normal. However, within aortic stenosis subjects, left ventricular RWT did not correlate with left ventricular systolic pressure or with aortic valve area.3. In subjects with aortic stenosis, left ventricular RWT was higher in those with ACE DD (P<0.05) or AGT T174M (P<0.06) compared with those with the ACE II or ID genotype or AGT TT174 genotype. No relationship was observed with any of the AT1 alleles. The ACE and AGT genetic markers independently predicted left ventricular RWT in aortic stenosis. No association was observed between these genotypes and left ventricular RWT in normal subjects.4. The data suggest that the AGT T174M and ACE I/D genotypes may act together to influence the degree of hypertrophy in subjects with aortic stenosis.5. In patients with aortic stenosis, genetic variants of proteins from the renin angiotensin system may be at least as important as left ventricular systolic pressure in determining the degree of left ventricular hypertrophy and could therefore explain the clinical variation observed in the progression to cardiac dysfunction.
PRODUCTION OF 18‐OXO‐CORTISOL IN SUBTYPES OF PRIMARY ALDOSTERONISM
Authors: Stowasser Michael , Bachmann Anthony W , Tunny Terry J , Gordon Richard D 
Published: June 2007

SUMMARY1. In familial hyperaldosteronism type I (FH‐I), expression of an adrenocorticotropic hormone (ACTH)‐dependent hybrid 11β‐hydroxylase/aldosterone synthase gene causes excessive ‘hybrid steroid’ (18‐hydroxy‐ and 18‐oxo‐cortisol) production. In order to study the mechanism of elevated ‘hybrid steroid’ levels in angiotensin‐unresponsive (AII‐U) aldosterone‐producing adenoma (APA), we compared responses of 24 h urinary 18‐oxo‐cortisol, aldosterone and cortisol to dexamethasone (0.5 mg q6h for 4 days) in 11 FH‐I patients, 11 patients with AII‐U APA, 11 patients with AII‐responsive (AII‐R) APA and 10 patients with bilateral adrenal hyperplasia (BAH).2. Consistent, marked suppression (by at least 60%) of 18‐oxo‐cortisol levels by dexamethasone was seen in all groups except AII‐U APA. Aldosterone levels were consistently suppressed to undetectable levels only in FH‐I. Cortisol levels were suppressed to undetectable levels in all patients except two with AII‐U APA.3. Production of both 18‐oxo‐cortisol and aldosterone (and occasionally cortisol) in AII‐U APA appears relatively ACTH‐independent, consistent with a common mechanism involved in the formation of these two steroids from their respective precursors, which differs from that in FH‐I.4. In AII‐R APA and BAH, 18‐oxo‐cortisol production appears markedly ACTH‐dependent, but aldosterone production is not.
α1‐ANTITRYPSIN DEFICIENCY ALLELES AND BLOOD PRESSURE IN AN AUSTRALIAN POPULATION
Authors: Huggard PR , West MJ , Summers KM 
Published: June 2007

SUMMARY1. Two deficiency alleles of α1‐antitrypsin (AAT) called S and Z have been previously associated with lower blood pressure levels.2. A sample of Australian hypertensive and normotensive subjects was investigated with respect to these alleles.3. No association of blood pressure levels with these AAT alleles was found in our study sample.
NON‐INVASIVE ASSESSMENT OF BAROREFLEX SENSITIVITY AND RELATION TO MEASURES OF HEART RATE VARIABILITY IN MAN
Authors: Pellizzer A‐M , Kamen PW , Jackman G. , Brazzale D. , Krum H. 
Published: June 2007

SUMMARY1. We have developed a simple noninvasive method to assess the spontaneous baroreflex (BRS; reflex heart rate response to change in systemic blood pressure) in man. The BRS is impaired in many cardiovascular disorders and is known to be of major prognostic significance; however, the invasive nature of traditional BRS assessment has thus far limited its clinical application.2. Sixteen healthy subjects (7M, 9F; age 28 ± 3 years) were studied at baseline and during stepwise i.v. infusion of phenylephrine and bolus i.v. dosing of nitroprusside. Invasive BRS was derived from linear regression of the change in systolic blood pressure (SBP) and RR interval from baseline following these perturbations. Noninvasive BRS was derived from approximately 1500 gated beat‐to‐beat SBP and RR interval data points acquired by Finapres BP and continuous ECG monitoring. Slopes were derived from linear regression of three consecutive baroreflex‐mediated data points (following a phase shift of one RR interval from its accompanying SBP value) and were averaged to determine BRS. Correlations between invasive and noninvasive BRS measures were found to be highly significant (r = 0.78; P= 0.0009; slope = 0.87).3. Significant correlations between noninvasively determined BRS and heart rate variability derived measures of autonomic activity (24h standard deviation of normal RR intervals, root mean square of successive RR intervals, low frequency and high frequency power) were also observed (r = 0.79–0.83; P= 0.003–0.008).4. These results support the validity of this noninvasive method of measurement of BRS in man and of a parasympathetic contribution to spontaneous baroreflex.
Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: HUMAN TYPE‐1 ANGIOTENSIN II (AT1) RECEPTOR GENE STRUCTURE AND FUNCTION
Authors: Curnow Kathleen M 
Published: June 2007

SUMMARY

The type‐1 angiotensin II (AngII) receptors, designated AT1, mediate most of the biological actions of the peptide hormone AngII. They are the most recent drug target for the treatment of hypertension and cardiac failure and basic research is now focusing on the mechanisms that regulate their expression.
In humans there is a single AT1 gene. It encodes a 47 kb pre‐mRNA containing five exons, with the previously described AT1 open reading frame (ORF) on exon 5. Alternative splicing results in the production of mature mRNA that are translated at different efficiencies and encode two receptor isoforms. The inclusion of exon 2 markedly inhibits translation of the downstream ORF, both in vitro and in vivo. Nonetheless, this exon is present in up to one‐half of AT1 mRNA in all tissues studied.
Transcripts containing exon 3 spliced to exon 5 encode a receptor with an amino‐terminal extension of 32 amino acids and represent up to one‐third of total AT1 mRNA in each tissue examined. In vitro, these latter transcripts are translated to produce a longer receptor and, in transfected cells, they encode a functional AT1 receptor with ligand‐binding and signalling properties similar to those of the short isoform.
Exon 4 is of minor significance as it is rarely spliced into AT1 mRNA.
These data indicate that, in addition to characterizing factors that modulate AT1 promoter activity and RNA stability, it is important to analyse the splicing patterns of this gene when studying the regulation of its expression.
EFFECTS OF ONE‐CLIP, ONE‐KIDNEY HYPERTENSION IN CHRONICALLY CATHETERIZED PREGNANT EWES
Authors: Lumbers ER , Burrell JH , Stevens AD , Weir BA 
Published: June 2007

SUMMARY1. Hypertension secondary to renal disease was studied in non‐pregnant and pregnant ewes to determine whether there were any changes in arterial pressure and the distribution of cardiac output and, in particular, whether uteroplacental blood flow was affected.2. In six non‐pregnant, chronically catheterized, uninephrec‐tomized ewes, a reduction in renal blood flow (RBF) to 40–50% of control caused hypertension within 3 h. This was maintained for as long as RBF was reduced (72 h) and returned to control 24 h after the occluder around the renal artery was released. When this experiment was repeated in 16 uninephrectomized pregnant ewes (118–134 days gestation) hypertension occurred within 3 h and was sustained for as long as RBF was reduced (between 24 and 72 h). Arterial pressure returned to control within 24–72 h of restoring RBF.3. Compared with non‐pregnant ewes, pregnant ewes had similar arterial pressures, higher cardiac outputs (CO; P < 0.001) and heart rates (HR; P < 0.001), lower total peripheral resistances (TPR; P < 0.001) and similar blood flows to brain, ovary, pancreas, kidney and spleen. Splenic vascular resistance (VR) was greater (P= 0.006), gut blood flow was greater (P < 0.05) and gut VR was less (P < 0.05). Myoendometrial blood flow/g was greater (P < 0.005) and myoendometrial VR was less (P= 0.006).4. In pregnant sheep with renal clip hypertension, there was no change in CO and HR, but TPR increased (P < 0.01), as did plasma renin activity. Gut, brain, pancreatic and myoendometrial VR were increased as long as RBF was reduced; in addition, myoendometrial VR remained high for the rest of the experiment. Placental blood flow was unchanged at 3h; 24–72 h later it was reduced (P < 0.05) and remained low. Placental VR was increased 24–72 h after RBF was restored when ewes were again normotensive.5. Thus, one‐clip, one‐kidney renal hypertension in the pregnant ewe was due to increased TPR associated with a fall in uteroplacental blood flow that persisted even when RBF was restored and ewes were normotensive. This reduction in uteroplacental blood flow could account for the high foetal morbidity and mortality that occurs in pregnant women with renovascular hypertension.
RENIN, PRORENIN, AND RENIN GENE EXPRESSION IN RATS WITH ACUTE NEPHROTIC SYNDROME
Authors: Ibarra‐Rubio Maria Elena , V Margarita Ramos , Correa‐Rotter Ricardo , Pedraza‐Chaverri Jose 
Published: June 2007

SUMMARY1. The concentration of total, active and inactive renin was analysed in plasma, urine and kidney from control (C), pair‐fed (PF) and nephrotic (NS) rats, as well as renin mRNA levels in kidney, liver and brain.2. Nephrotic syndrome were induced by a single subcutaneous injection of puromycin aminonucleoside (PAN) and determinations were made 6 days after PAN injection.3. Plasma total renin did not change, active renin increased in NS rats with respect to PF and C groups and in PF rats with respect to C. In contrast, the inactive renin percentage decreased in NS rats with respect to PF and C groups and in PF animals with respect to C. Total, active and inactive renal renin content did not change and active and inactive renin were significantly excreted by urine with no changes in the prorenin percentage with respect to C and PF groups.4. In both NS and PF groups, renin mRNA levels did not change in any of the tissues studied. In another group of rats, kidney renin mRNA levels were measured on days 1, 3, 5 and 7 after PAN injection and no time‐course changes in its expression were found.5. These results suggest that renin gene expression is not altered in acute nephrotic syndrome and that plasma renin concentration is regulated at the translational or post‐translational level in this experimental model.
DIURNAL EFFECTS OF FLUOXETINE AND NALOXONE ON THE HUMAN HYPOTHALAMIC‐PITUITARY‐ADRENAL AXIS
Authors: Torpy DJ , Grice JE , Hockings GI , Walters MM , Crosbie GV , Jackson RV 
Published: June 2007

SUMMARY1. Central serotonergic pathways are hypothesized to be involved in the stimulation of hypothalamic adrenocorticotropic hormone (ACTH) secretagogue release by both circadian‐ and stress‐induced mechanisms. We aimed to investigate this hypothesis by measuring the effect of the highly specific serotonin re‐uptake inhibitor fluoxetine (FX) on ACTH and Cortisol release in the morning and in the afternoon in humans, both by itself and in combination with the opioid antagonist naloxone (Nal). Naloxone causes ACTH release in humans by removing an endogenous inhibitory opioid tone on central noradrenergic pathways stimulatory to hypothalamic corticotropin‐releasing hormone (CRH) secretion. Serotonergic agents may act directly or indirectly through these central noradrenergic pathways and, if so, would be expected to be additive to or synergistic with Nal in causing ACTH and Cortisol release.2. Oral FX (40 mg) was given at approximately 07.00 or 11.00 h, either alone or with intravenous Nal 3 h later, to normal human volunteers. Plasma ACTH and Cortisol levels were measured for 5 h after FX dosing.3. Fluoxetine produced a small but non‐significant increase in Nal‐stiimilated ACTH and Cortisol release in both morning and afternoon studies. Naloxone alone did not cause different ACTH and Cortisol responses in the morning and afternoon.4. These results suggest that serotonergic pathways are not major regulators of the hypothalamic‐pituitary‐adrenal axis in humans or that FX has counteracting acute inhibitory effects on the axis, such as inhibition of hypothalamic arginine vasopressin secretion, which has been demonstrated in chronic animal studies.
EFFECTS OF 17P‐OESTRADIOL ON VASCULAR RESPONSES IN THE IN SITU BLOOD‐PERFUSED MESENTERY OF WISTAR‐KYOTO RATS
Authors: Chu ZM , Beilin LJ 
Published: June 2007

SUMMARY1. To determine whether endogenous oestrogen plays a role in pregnancy induced decreased vascular reactivity we have examined the effects of 173‐oestradiol on vasoconstrictor responses to various stimuli using an in situ blood‐perfused mesenteric vascular preparation in Wistar‐Kyoto (WKY) rats.2. Daily administration of 17β‐oestradiol (500 μg/kg, s.c.) for 15 days significantly enhanced mesenteric vasoconstrictor responses to noradrenaline (NA), without affecting responses to the electrical stimulation of sympathetic nerves (ES) and angiotensin II (AngII).3. Nitric oxide (NO) synthesis inhibition by nitro‐L‐arginine methyl ester (L‐NAME; 100 mg/kg, i.v.) significantly potentiated mesenteric vasoconstrictor responses to all stimuli in both 173‐oestradiol‐treated and control animals. The difference in NA responses between groups was diminished following NO synthesis inhibition.4. These findings do not support the hypothesis that increased endogenous oestrogen plays a role in decreased mesenteric vascular reactivity in pregnancy. However, responses to oestrogen may be dose‐dependent and enhancement of vasoconstrictor responses to NA may be relevant to oral contraceptive‐induced hypertension.
ALTERATIONS OF CARDIAC α‐ADRENOCEPTOR SUBTYPES IN HYPOTHYROID RATS
Authors: Zhang Youyi , Xu Kaiming , Han Chide 
Published: June 2007

SUMMARY1. Alterations in the cardiac ai‐adrenoceptor and its subtypes in hypothyroid rats were studied by radioligand binding assays and reverse transcription‐polymerase chain reaction (RT‐PCR). Hypothyroidism was created by feeding rats with 0.2% 2‐thiouraciI solution instead of daily drinking water for 20 days.2. The density of cardiac α1‐adrenoceptors (Bmax) was increased from 67.5 ± 4.3 fmol/mg in control rats to 81.1 ± 7.2 fmol/mg (P < 0.05) in hypothyroid rats.3. Compared with control rats, in hypothyroid rats the percentages of high‐affinity sites for (+)‐niguldipine and 5‐methyl‐urapidil were increased from 13.8 ± 5.6 and 31.9 ± 6.3%, respectively, to 24.9 ± 73 and 45.5 ± 2.4%, respectively (both P < 0.05), while those for BMY7378 were decreased from 37.2 ± 8.9 to 23.8 ± 8.4% (P < 0.05), respectively. The percentage of high‐affinity sites for WB4101 was not significantly different in control and hypothyroid rats (43.3 ± 9.1 and 39.4 ± 3.6%, respectively).4. Reverse transcription‐PCR experiments revealed that the steady state levels of mRNA for otiA‐ and am‐adrenoceptors were increased, while those for ctiD‐adrenoceptor were decreased in the hearts of hypothyroid rats.5. The concentration‐contraction response curves for noradrenaline in the presence of a β‐adrenoceptor antagonist in control and hypothyroid rats showed that the maximal response was reduced from 344 ± 58 to 200 ± 23 mg, respectively (P < 0.05).6. The data suggest that in hypothyroid rats the total number of cardiac ai‐adrenoceptors is increased. The change is subtype‐selective, with levels of ctiA‐ and am‐adrenoceptors being increased and levels of aiD‐adrenoceptors being reduced. Furthermore, the positive inotropic response mediated by a i‐adrenoceptors is reduced in hypothyroid rats.
A LOW DOSE OF STREPTOZOTOCIN PREVENTS KAINIC ACID‐INDUCED SEIZURES AND LETHAL EFFECTS IN THE RAT
Authors: Kim Hyoung‐Chun , Im Doo‐Hyun , Jhoo Wang‐Kee , Kim Chin , Wie Myung‐Bok 
Published: June 2007

SUMMARY1. The effect of streptozotocin (STZ), a nitric oxide (NO) donor, on kainic acid (KA)‐induced neurotoxicity was examined in Sprague‐Dawley rats.2. The administration of KA (8mg/kg, i.p.) produced significant neurotoxicity accompanied with increased immuno‐reactivity for Fos‐related antigen in the rat hippocampus.3. Pretreatment with STZ (15mg/kg, i.m.) significantly blocked the neurotoxicity induced by KA.4. Thus, the neuroprotective effect of STZ may, at least in part, reflect the role of NO in inhibiting seizures.