bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANGIOTENSIN‐RESPONSIVEALDOSTERONE‐PRODUCING ADENOMAS: POSTOPERATIVE DISAPPEARANCE OF ALDOSTERONE RESPONSE TO ANGIOTENSIN
Authors: Tunny Terry J. , Klemm Shelley A. , Stowasser Michael , Gordon Richard D. 
Published: June 2007

SUMMARY1. Nineteen out of 47 patients (40%) with confirmed unilateral aldosterone‐producing adenoma (APA) were responsive to low‐dose angiotensin II infusion (AH‐R), as defined by an increase in plasma aldosterone concentration of >50% over basal at 2 ng/kg per min for 60 min.2. Seven to ten days after unilateral adrenalectomy, aldosterone was no longer responsive to angiotensin infusion in AII‐R APA (100%, n = 17). Therefore, angiotensin responsiveness resides within the adenoma in AII‐R APA.3. The upright posture test for the differentiation of adenoma from hyperplasia was unreliable for the AII‐R APA (26%), but generally reliable in the angiotensin‐unresponsive subtype, (AH‐U APA, 96%).4. The reported predominance of females in APA was seen in AII‐U APA (68%), but was reversed in AII‐R APA (37%).
ENALAPRILAT RESTORES SENSITIVITY OF BAROREFLEX CONTROL OF RENAL AND TOTAL NORADRENALINE SPILLOVER IN HEART FAILURE RABBIT
Authors: Noshiro Takao , Way Diana , Miura Yukio , McCrath Barry P. 
Published: June 2007

SUMMARY1. The acute effect of an angiotensin converting enzyme inhibitor (ACEI), enalaprilat, on baroreflex‐mediated changes in renal and total NA spillover rate in conscious rabbits with doxorubicin‐induced cardiomyopathic congestive heart failure (CHF) were investigated under resting conditions and in response to changes in arterial pressure induced by sodium nitroprusside and phenylephrine infusions.2. Six saline‐treated (N group) and 11 doxorubicin‐treated rabbits (1 mg/kg administered i.v. twice weekly) were studied after 4 and 6 weeks treatment. Five CHF rabbits received saline (C group) and six enalaprilat infusion (ACEI group).3. After 4 weeks of doxorubicin, mean arterial pressure (MAP)‐renal noradrenaline (NA) spillover and MAP‐total NA spillover curves did not change during enalaprilat infusion.4. After 6 weeks, the C group showed blunted MAP‐renal NA spillover and MAP‐total NA spillover curves. In the ACEI group, however, both curves returned toward those seen in the N group (slope of MAP‐renal NA curve: from 0.27 to 1.80 ng/min per mmHg, MAP‐total NA curve: from 1.61 to 3.59 ng/min per mmHg).5. Results of this study indicate that enalaprilat enhances baroreflex control of renal and total NA spillover in rabbits with CHF and further support the view that activation of the renin‐angiotensin system contributes significantly to the attenuated baroreflex responses in CHF.
METABOLIC STUDIES OF URIDINE IN RATS WITH DOCA‐SALT HYPERTENSION AND ON HIGH SODIUM DIET
Authors: Hasnain Quloobul , Macdonald Graham 
Published: June 2007

SUMMARY1. The steady‐state metabolic clearance and calculated secretion rate of the pyrimidine nucleoside uridine were studied by equilibrium infusion in normal rats, rats on a high sodium diet, rats made hypertensive by subcutaneous injection of deoxycorticosterone acetate (DOCA), unilateral nephrectomy and high sodium drinking fluid, and two control groups of rats for the hypertensive group.2. Basal plasma uridine concentration in DOCA‐salt hypertension rats was found to be significantly reduced to 3.99 ± 0.31 pmol/L (mean ± s.e.m.) compared with control rats (11.98 ±1.64 μmol/L). Metabolic clearance (MCR) in DOCA‐salt hypertensive rats was significantly raised (200.54±10.77 mL/kg per min) compared with control rats (65.17 ± 1.99 mL/kg per min). No difference was found in plasma uridine concentration and MCR among the other two control groups and high sodium diet rats. Calculated secretion rate was unchanged in all animals. No significant differences were found between different groups of rats in blood pressure responses to uridine.3. The raised metabolic clearance and reduced plasma uridine concentration in DOCA‐salt hypertension may be consistent with increased intracellular transport and phosphorylation of uridine to the physiologically active compound uridine monophosphate (UMP) which would lead to arteriolar constriction, hypertension and natriuresis. The results contrast with those in humans with extracellular fluid (ECF) expansion from endstage renal failure and rats with one‐kidney, one‐clip (1K1C) hypertension but are not due to the pharmacological effects of deoxycorticosterone. The difference may be due to the haemodynamic consequences of reduced renal perfusion pressure or reduced renal mass compared with DOCA‐salt model.
THE INTRARENAL SITE OF CALCITONIN GENE‐RELATED PEPTIDE DEGRADATION IN THE ISOLATED PERFUSED RAT KIDNEY
Authors: Rubinstein C. , Fletcher D. R. , Shulkes A. 
Published: June 2007

SUMMARY1. Calcitonin gene‐related peptide (CGRP) is a potent vaso‐active 37 amino acid peptide, typically elevated in plasma from patients with medullary thyroid cancer (MTC), but undetectable in the plasma of normal subjects.2. The kidney is a major site for the clearance of exogenously infused CGRP but the intrarenal site of this clearance is unknown. Extra‐organ clearance is also significant for CGRP, and whereas the site and mechanism of this degradation remain uncertain, the vasculature has been postulated as the most likely site.3. The isolated perfused rat kidney (IPRK) was studied to (i) localize the intrarenal site of CGRP clearance and (ii) determine the contribution of the renal vasculature to the clearance of CGRP. The half‐life of CGRP in the filtering IPRK was 63.9 ± 4.5 min, whereas blocking of filtration by elevation of the perfusate osmolarity abolished the degradation. This suggests that (i) renal CGRP degradation occurs after glomerular filtration with intratubular metabolism and (ii) that there is no active CGRP degradation in the (glomerular) capillary endothelium.4. These results do not support the theory that renal vascular endothelium plays a major active role in CGRP degradation.
HAEMODYNAMIC AND HUMORAL CONSEQUENCES OF CHRONIC INFUSION OF VASOPRESSIN IN CONSCIOUS RATS
Authors: Tsuchihashi Takuya , Takata Yutaka , Nakao Yae , Tominaga Mitsuhiro , Takishita Shuichi , Kobayashi Kazuo , Abe Isao , Fujishima Masatoshi 
Published: June 2007

SUMMARY1. To determine the long‐term haemodynamic and humoral effects of arginine vasopressin (AVP), a chronic intravenous infusion of AVP was performed in conscious Wistar normotensive rats.2. AVP (1, 10, 50 or 100 ng/h) or saline as a vehicle control was infused continuously into the right jugular vein at a rate of 1 μL/h using an osmotic minipump for 7 days.3. As a result, significant elevations of systolic blood pressure were observed in association with increases in plasma AVP concentration. Significant decreases in heart rate were observed during infusion of 100 ng/h of AVP. Mean arterial pressures measured directly on the sixth day of infusion were significantly higher in the rats given 50 ng/h (125 ± 3 mmHg) or 100 ng/h (125 ± 2 mmHg) compared with control rats (117 ± 2 mmHg). Intravenous injection of the V1 antagonist, d(CH2)5Tyr(Me)AVP, significantly reduced the elevated mean arterial pressure induced by 50 or 100 ng/h of AVP (—7 ± 4 and—11 ± 2 mmHg, respectively). Plasma renin and norepinephrine concentrations were not affected by AVP infusion, while plasma epinephrine concentration was lower in the rats given 100 ng/h of AVP. Intravenous infusion of AVP did not alter bodyweight, serum electrolytes or osmolality.4. These results suggest that AVP has a long‐term pressor effect which is attributable to its vasoconstrictor action in conscious rats.
THE INHIBITORY EFFECT OF SA3443, A NOVEL CYCLIC DISULFIDE COMPOUND, ON ALPHA‐NAPHTHYL ISOTHIOCYANATE‐INDUCED INTRAHEPATIC CHOLESTASIS IN RATS
Authors: Tanaka M. , Nakata K. , Mita S. 
Published: June 2007

SUMMARY1. We investigated the effect of SA3443, a novel cyclic disulfide compound, on alpha‐naphthyl isothiocyanate (ANIT)‐induced intrahepatic cholestasis in rats.2. SA3443 given orally at doses of 100 or 300 mg/kg, three times at 4h intervals, dosedependently suppressed the elevation of serum total bilirubin, alkaline phosphatase activity and transaminase activities induced by administration of ANIT (80 mg/kg) 3 h before the second dosages of SA3443.3. SA3443 also significantly inhibited the reduction of bile flow in the ANIT‐treated rats.4. These findings indicated that SA3443 had a markedly inhibitory effect on ANIT‐induced intrahepatic cholestasis in rats.
USE OF A COMPUTERIZED POSTURAL SWAY MEASUREMENT SYSTEM FOR ASSESSING WORKERS EXPOSED TO MANGANESE
Authors: Chia S. E. , Goh J. , Lee G. , Foo S. C. , Gan S. L. , Bose K. , Jeyaratnam J. 
Published: June 2007

SUMMARY1. Computerized postural sway measurement systems have been used recently in human physiology and pharmacology for determining postural stability, but their applicability for the assessment of the effects of exposure to neurotoxic agents is lacking.2. We have examined the feasibility of using a computerized postural sway measurement system to assess the postural sway parameters of manganese exposed workers compared with a control group.3. Sway parameter data were collected using a kislter multicomponent measuring platform (Type 9281B) connected to vicon motion analysis system for 13 exposed and 16 control subjects.4. Significant differences in several of the sway parameters (Px, Py—mean distance (mm), from the centre of the platform along the X‐axis [anterior‐posterior movement] and Y‐axis [lateral movement], respectively) between the exposed and control groups were observed even after adjustment for possible confounders. Computerized postural sway measurement system may be a useful method of assessing workers exposed to neurotoxic agents affecting posture.
RELEASE OF A SUBSTANCE FROM THE HUMAN PLACENTA HAVING DIGOXIN‐LIKE IMMUNOREACTIVITY
Authors: Grande A. Di , Boura A. L. A. , Read M. A. , Malatino L. S. , Walters W. A. W. 
Published: June 2007

SUMMARY1. The human placental lobule, perfused with a constant flow (5 mL/min) of Krebs’ solution after delivery at term, released into the fetal perfusate a digoxin‐like substance, as measured by a fluorescence polarization immunoassay.2. Initially the venous concentration was 360 ± 66.7 pmol/ L digoxin equivalents. This level did not change significantly during fetal vasoconstriction induced by prostaglandin F2α infusion and persisted for the duration of the experiment (1.5–2h).3. Infusion into the fetal circulation of Fab fragments of sheep antibodies to digoxin caused vasodilatation, indicated by a fall in perfusion pressure.4. Thus a digoxin‐like immunoreactive substance, previously reported to be present in the placenta, is released into the fetal circulation and may play a role in placental control of fetal vascular tone.
CARDIAC BAROREFLEXES AND HYPERTENSION
Authors: Head Geoffrey A. 
Published: June 2007

SUMMARY1. The role of cardiac reflexes in baroreflex control mechanisms and the changes that occur in chronic hypertension is reviewed. The rapid resetting properties of the arterial baroreceptors ensures its role in short‐term rather than long‐term control of blood pressure.2. In hypertensive humans and animals, the baroreceptor‐heart rate reflex has diminished sensitivity due mainly to reduced maximum capacity of the cardiac vagal component rather than a change to the sympathetic.3. The development of this vagal deficit in spontaneously hypertensive rats (SHR) coincides with the onset of cardiac hypertrophy rather than vascular hypertrophy. A combination of chronic perindopril treatment regimens in young and older SHR showed that the vagal deficit was better correlated with the degree of cardiac hypertrophy than with other variables such as blood pressure, hypertension or indices of vascular hypertrophy. Similar results have been shown for renovascular hypertension in rats.4. The bradycardia produced by electrical stimulation of the vagus in urethane anaesthetized young SHR was enhanced compared to Wistar‐Kyoto rats (WKY) while responses observed in adult SHR and WKY were similar, suggesting that the vagal deficit in hypertensive rats is not due to a defect in the efferent arm of the baroreflex.5. The association of the vagal deficit with cardiac hypertrophy, but not with the vagal efferent pathways, suggests an important role for cardiac afferents in hypertension in mediating the baroreflex deficit.6. A diminished baroreflex and also a reduced heart rate variability is an independent risk factor for sudden death following myocardial infarction. Thus, antihypertensive therapy, which more effectively reduces cardiac hypertrophy, should have a desirable effect on baroreceptor reflexes and therefore in reducing blood pressure variability.
ION CHANNEL MODULATORS AS POTENTIAL POSITIVE INOTROPIC COMPOUNDS FOR TREATMENT OF HEART FAILURE
Authors: Doggrell Sheila , Hoey Andrew , Brown Lindsay 
Published: June 2007

SUMMARY1. Current positive inotropy therapy of heart failure is associated with major problems: digoxin and the phosphodiesterase inhibitors can cause life‐threatening toxicity while β‐adrenoceptor agonists become less effective inotropic compounds as heart failure progresses. A new approach to positive inotropy is ion channel modulation.2. An increased influx of Na+ during the cardiac action potential, as measured with DPI 201–106 and BDF 9148 which increase the probability of the open state of the Na+ channel, will increase force of contraction.3. Activation of L‐type Ca2+ channels with Bay K 8644 will increase influx of Ca2+ and increase the force of contraction. However the Ca2+ channel activators developed to date have little potential for the treatment of heart failure as they are vasoconstrictors.4. Blocking cardiac K+ channels is a possible mechanism of positive inotropy. Terikalant inhibits the inward rectifying K+ channel, tedisamil inhibits the transient outward K+ channel and dofetilide is one of the newly developed inhibitors of the slow delayed outward rectifying K+ channel. All these drugs prolong the cardiac action potential to increase Ca2+ entry and force of contraction.5. Thus drugs which increase Na+ influx or block K+ channels represent exciting possibilities for positive inotropy and the potential of these compounds for the treatment of heart failure needs to be fully evaluated.
SODIUM LOADS ENHANCE THE NATRIURETIC RESPONSES TO ATRIAL NATRIURETIC PEPTIDE AND NEUTRAL ENDOPEPTIDASE INHIBITORS IN CONSCIOUS CYNOMOLGUS MONKEYS
Authors: Seymour Andrea A. , Asaad Magdi M. , Abboa‐Offei Benoni , Smith Patricia L. , Rogers W. Lynn 
Published: June 2007

SUMMARY1. The effects of sodium supplements on the renal responses to human atrial natriuretic peptide (hANP 99–126) and to the selective inhibitors of neutral endopeptidase 3.4.24.11 (NEP) SQ 28 603 and candoxatrilat were determined in conscious monkeys.2. When the monkeys’ diet was changed from 0.55% sodium to 1.1% sodium, the natriuretic response to 100 μmol/kg intravenous of SQ 28603 increased from 665 ± 64 to 1015 ± 224 μEq/3h. An acute oral load of 25 mEq sodium significantly increased the natriuresis stimulated by 300 pmol/kg, P.o., of SQ 28603 from 700 ± 332 μEq/3h in normal monkeys to 2437 ± 841 μEq/3h. Therefore, the non‐human primate model was appropriate for investigating the effects of sodium loads on the urinary ANP and cGMP responses to exogenous ANP in the presence and absence of NEP inhibitors.3. Graded intravenous infusions of saline increased basal urine volume and excretion of sodium and ANP. Salt supplements enhanced the diuretic, natriuretic and ANP responses to 0.3 nmol/kg intravenous of hANP 99–126 in monkeys treated with vehicle or 10 μmol/kg intravenous of candoxatrilat. The sodium and ANP excretions stimulated by hANP 99–126 were positively correlated with each other and with the calculated intravenous sodium load in the presence or absence of candoxatrilat.4. SQ 28 603 and candoxatrilat (0.3 to 10 μmol/kg intravenous) each produced significant, dose‐related potentiation of the natriuretic, cGMP and ANP responses to 0.3 nmol/kg intravenous of hANP 99–126 in monkeys receiving 5 mL/kg + 0.2 mL/min saline. In addition, the highest dose of SQ 28 603 produced significant depressor activity.5. In conclusion, the increased natriuretic activity of hANP 99–126 in sodium loaded monkeys was mediated, in part, by increased ANP delivery to the guanylate cyclase linked ANP receptors in the distal renal tubules.
THE EFFECTS OF CENTRAL ADMINISTRATION OF ω‐CONOTOXIN GVIA ON CARDIOVASCULAR PARAMETERS AND AUTONOMIC REFLEXES IN CONSCIOUS RABBITS
Authors: Whorlow Sarah L. , Angus James A. , Wright Christine E. 
Published: June 2007

SUMMARY1. The effects of central administration of ω‐conotoxin GVIA (ω‐CTX), an N‐type calcium channel blocker, were examined in conscious rabbits implanted with lateral intracerebroventricular (i.c.v.) cannulae.2. Experiments were performed over 4 consecutive days. On day 1, the baroreceptor heart rate (induced by glyceryl trinitrate and phenylephrine) and Bezold‐Jarisch like (elicited by serotonin) reflexes were measured before (0 h) and 2 h after central administration of ω‐CTX (3 or 30 pmol/ kg, i.c.v.) or vehicle. On days 2–4, resting parameters and reflexes were again monitored but no further ω‐CTX was administered.3. No change in heart rate (HR) was observed in any rabbit treatment group during the experimental period. In the vehicle (n= 6) and ω‐CTX 3 pmol/kg (n = 6) groups, small falls in mean arterial pressure (MAP) of 6 ± 2 and 10 ± 3 mmHg, respectively, occurred between 0 and 24 h; MAP then remained stable. Baroreceptor‐heart rate reflex curve parameters did not change in either of these groups during the 4 day period.4. Following administration of w‐CTX 30 pmol/kg (n = 7), MAP decreased progressively and by 48 h had fallen by 19 ± 4 mmHg. Also at 48 h, a 20% decrease in HR range of the baroreceptor‐heart rate reflex curve was seen without any change in the lower HR plateau from the 0 h control. This indicates that there was an attenuation of the sympathetically mediated upper component of the curve while the vagally mediated component was unaffected.5. The Bezold‐Jarisch like reflex‐induced bradycardia, mediated by the efferent vagus nerve, was unaffected by i.c.v. administration of vehicle or either dose of ω‐CTX.6. Therefore, central administration of ω‐CTX resulted in a slowly developing hypotensive response consistent with a sympatholytic action while vagally mediated reflexes were unaffected.
HIGH FISH OIL DIET INCREASES OXIDATIVE STRESS POTENTIAL IN MAMMARY GLAND OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Mehta R. S. , Gunnett C. A. , Harris S. R. , Bunce O. R. , Hartle D. K. 
Published: June 2007

SUMMARY1. The purpose of this study was to determine whether high ω‐3 (19% menhaden oil, 1% corn oil) or high ω‐6 (20% corn oil) fatty acid diets would decrease expression of hypertension in the female spontaneously hypertensive rat (SHR), promote tumourigenesis in the rat 7,12‐dimethyl‐benz[a]anthracene (DMBA) model of mammary cancer or increase the susceptibility of the mammary gland to lipid peroxidation. A group of rats on a 5% corn oil diet served as the low fat control group.2. We found that the high ω‐3 and high ω‐6 fatty acid diets did not significantly decrease mean arterial pressure. Marked differences occurred between the effects of ω‐3 and ω‐6 high fatty acid diets on baseline oxidation, auto‐oxidation and iron‐ascorbate catalyzed oxidation. The ω‐3 diet showed 675% increase in basal oxidation, a 2624% increase in auto‐oxidation and a 4244% increase in iron‐ascorbate catalyzed oxidation compared to the ω‐6 diet in mammary tissue homogenates. Although all rats were given 5 mg DMBA (i.g.), no mammary tumours were observed in any of the dietary groups.3. We conclude that: (i) high polyunsaturated fatty acid diets do not decrease blood pressure in the female SHR; (ii) high fish oil diet markedly increases oxidative potential in the mammary gland; and (iii) the female SHR is resistant to DMBA‐induced tumourigenesis.
GENETICS OF PRIMARY ALDOSTERONISM
Authors: Gordon Richard D. , Klemm Shelley A. , Tunny Terry J. , Stowasser Michael 
Published: June 2007

SUMMARY1. In 1991 we described a familial variety of primary hyperaldosteronism which was not glucocorticoid‐suppressible and was associated with adenoma formation, and called it familial hyperaldosteronism type II (FH‐II) in order to distinguish it from the glucocorticoid‐suppressible variety described in 1966, familial hyperaldosteronism type I (FH‐I).2. In 1992 the genetic basis of FH‐I was clarified by description of a hybrid gene.3. Primary aldosteronism due to bilateral adrenocortical hyperplasia or to aldosterone‐producing tumour can be part of the multiple endocrine neoplasia type I syndrome (MEN I), in which loss of heterozygosity has been described on chromosome 11q13. Loss of heterozygosity at the MEN I locus was found in five of 26 aldosterone‐producing tumours from our series (by Japanese collaborators). These included two with adrenal cancer and two with FH‐II.4. We recently described an association of aldosterone responsiveness of aldosterone‐producing adenomas with renin gene restriction fragment length polymorphisms, suggesting a possible role for renin genotype and intra‐adrenal renin gene expression in the development and biochemical expression of some aldosterone‐producing tumours.5. We found abnormal karyotypes in 13 of 32 benign aldosterone‐producing adenomas.
P‐GLYCOPROTEIN EXPRESSION IN CLASSICAL MULTI‐DRUG RESISTANT LEUKAEMIA CELLS DOES NOT CORRELATE WITH ENHANCED CHLORIDE CHANNEL ACTIVITY
Authors: Wang Xueyong , Wall Dominic M. , Parkin John D. , Zalcberg John R. , Kemm Robert E. 
Published: June 2007

SUMMARY1. P‐glycoprotein (Pgp) is an ATP‐dependent drug efflux pump responsible for classical multi‐drug resistance (MDR).2. Pgp is part of a supergene family of membrane transport proteins that includes the cystic fibrosis gene product.3. Transfection of cells with the MDRl gene has been previously shown to generate volume‐regulated chloride channel activity in association with Pgp expression.4. We have used whole‐cell patch clamping to examine the drug‐sensitive T lymphoblastic cell line CEM‐CCRF and its classical MDR derivative CEM/VLB100. The results suggest that expression of Pgp is not associated with increased chloride channel activity in this multi‐drug resistant cell line.5. We were unable to confirm previously reported results in MDRl transfected cell lines that suggested that Pgp was associated with the presence of volume‐regulated chloride channels.
RAT AORTIC SMOOTH MUSCLE CELLS EXPRESSING CHARYBDOTOXIN‐SENSITIVE POTASSIUM CHANNELS EXHIBIT ENHANCED PROLIFERATIVE RESPONSES
Authors: Neylon Craig B. , Avdonin Pavel V. , Larsen Michelle A. , Bobik Alex 
Published: June 2007

SUMMARY1. The relationship between the expression of potassium (K+) channels and the growth properties of cultured vascular smooth muscle cells was examined.2. Two groups of cells having different proliferative rates were cultured from the Wistar‐Kyoto rat aorta. One group of cells, derived from early passages (3–3, proliferated with a cell doubling time of 2.41 days. A second group of cells, derived from late passages (> 12), proliferated at a higher rate (cell doubling time, 0.61 days).3. Exposure of the early passaged cells to endothelin‐1 (0.1 pmol/L) induced membrane depolarization. In contrast, exposure of the late passage cells to endothelin‐1 (0.1 pmol/L) evoked a rapid hyperpolarization. The hyperpolarization in the late passage cells was blocked by charybdotoxin (20 nmol/L), an inhibitor of the large‐conductance Calcium (Ca)‐activated K+ channel.4. The authors conclude that rapidly proliferating vascular smooth muscle cells express enhanced activity of Ca‐activated K+ channels causing marked alterations in the electrical properties of the cells. It is therefore suggested that the reported increase in Ca‐activated K+ channel activity in the aortae of hypertensive rats is likely to be associated with the increased proliferative ability of the vascular smooth muscle cells.