bluuebunny/crossref_metadata_2025_split huggingface dataset:
AUTACOIDS AND CONTROL OF HUMAN PLACENTAL BLOOD FLOW
Authors: Boura A. L. A. , Walters W. A. W. , Read M. A. , Leitch I. M. 
Published: June 2007

SUMMARY1. Humans have a haemochorial, villous placenta. Uterine blood passes through maternal sinuses, bathing placental villi through which fetal blood circulates. Blood flow through each circulation is high and vascular resistance low. This haemodynamic situation is essential for efficient placental function.2. The low placental vascular resistance is due to a lack of nervous influences together with pregnancy‐induced changes promoting vasodilatation. Increases occur in output of the vasodilators prostacyclin and nitric oxide and also in membrane sodium pump activity.3. Many autacoids are present in umbilical blood. Fetal vessels of the placenta develop intense vasoconstriction in the presence of some autacoids, such as thromboxane A2 and prostaglandins F2α and E2, and respond weakly to others, such as angiotensin II and 5‐hydroxytryptamine. Nevertheless, vasodilator influences predominate.4. The diseases of pre‐eclampsia and fetal growth retardation are associated with reduced output of nitric oxide and prostacyclin and with increased production of thromboxane A2 and endothelin‐1. These changes promote vasoconstriction, increased vascular sensitivity to vasoconstrictor stimuli, platelet aggregation and intravascular coagulation, retarding blood flow and feto‐placental growth.5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in pre‐eclampsia and fetal growth retardation. Improved drug therapy is likely as knowledge increases of the importance of autacoids in normal placental function and in the changes that occur during disease.
THERAPEUTIC RESTORATION OF ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLAEMIC SUBJECTS: EFFECT OF FISH OILS
Authors: Chin Jaye P. F. , Dart Anthony M. 
Published: June 2007

SUMMARY1. Endothelial dysfunction, evidenced as an impaired response to acetylcholine, is well documented in hypercholesterolaemic subjects. We examined the ability of dietary supplementation with fish oils to restore endothelial function in forearm resistance vessels in these patients and compared this with restoration by lipid‐lowering therapy.2. Responses of forearm blood flow to acetylcholine (4.6, 9.25, 18.5 and 37 μg/min) and sodium nitroprusside (200, 400, 800 and 1600 ng/min) were obtained using forearm venous occlusion plethysmography in nine hypercholesterolaemic and seven age‐matched control subjects. The dose—response curve to acetylcholine was significantly blunted in hypercholesterolaemic subjects when compared with controls (P<0.001). Responses to sodium nitroprusside were not different between the two groups (P= 0.37).3. Lipid‐lowering therapy decreased total plasma cholesterol levels by 33% and significantly augmented the responses to acetylcholine (P = 0.001) but not to sodium nitroprusside in the hypercholesterolaemic subjects.4. Dietary supplementation with fish oils had no effect on either total or low density lipoprotein‐cholesterol but significantly augmented the responses to acetylcholine (P= 0.011) in hypercholesterolaemic subjects. Responses to sodium nitroprusside were not altered (P= 0.94).5. This study shows that endothelium‐dependent relaxation is impaired in subjects with high cholesterol levels and that this impairment can be reversed by lowering low density lipoproteins (LDL) cholesterol levels. In addition, we demonstrate that restoration of endothelial function can occur without changes in LDL levels, by dietary supplementation with fish oils.
LONG‐TERM CLENBUTEROL ADMINISTRATION ALTERS THE ISOMETRIC CONTRACTILE PROPERTIES OF SKELETAL MUSCLE FROM NORMAL AND DYSTROPHIN‐DEFICIENT MDX MICE
Authors: Hayes Alan , Williams David A. 
Published: June 2007

SUMMARY1. This study was designed to establish whether long‐term treatment with the powerful anabolic agent clenbuterol has beneficial effects on dystrophin‐deficient skeletal muscle function.2. Normal (C57BL/10) and dystrophic (mdx) mice were administered clenbuterol (2 mg/kg per day) for 15 weeks. At 20 weeks of age, the extensor digitorum longus (EDL) and soleus muscles were removed, and their contractile and histochemical properties analysed.3. Absolute and relative muscle masses were larger (P<0.001) in mdx compared to C57BL/10 mice. These larger muscles produced larger absolute forces (P<0.01) in the soleus of mdx mice compared to normal mice. Relative tetanic force was also larger (P<0.05) in the soleus of mdx mice. In contrast, the absolute tetanic tension of the EDL was reduced (P<0.01) in mdx mice compared to C57BL/10 mice, and both relative twitch and tetanic tensions were also lower (P<0.001) in mdx mice.4. Clenbuterol increased the lean muscle mass in both normal (10%, P<0.05 and 20%, P<0.01 for the EDL and soleus, respectively) and dystrophic (7%, P<0.05 and 11%, P<0.01) groups. Twitch contraction times were significantly faster in both the EDL (P<0.001) and soleus (P<0.01) muscles following clenbuterol administration, supported by fibre‐type transitions towards fast‐twitch fibres. Relative force levels of the soleus muscle of both C57BL/10 (40%, P<0.01) and rndx (20%, P<0.01) mice were increased significantly following clenbuterol treatment. No changes in the absolute or relative forces of the EDL muscles were observed in response to clenbuterol administration.5. Clenbuterol was thus able to increase the force output of a slow‐twitch, mixed (hence humanlike) muscle but not fast‐twitch muscle from mdx mice. The results lend tentative support to the potential role of clenbuterol as an anabolic agent in the treatment of muscle wasting diseases.
ANGIOTENSIN RECEPTORS IN CARDIOVASCULAR DISEASES
Authors: Brown Lindsay , Sernia Conrad 
Published: June 2007

SUMMARY1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix.2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases.3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density.4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density.5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists.6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients.7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype‐selective agonists and antagonists to treat particular forms of cardiovascular diseases.
KYNURENIC ACID, AN ENDOGENOUS GLUTAMATE ANTAGONIST, IN SHR AND WKY RATS: POSSIBLE ROLE IN CENTRAL BLOOD PRESSURE REGULATION
Authors: Kapoor Vimal , Kapoor Ranjna , Chalmers John 
Published: June 2007

SUMMARY1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro‐dissected regions of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar‐Kyoto rats: WKY).2. Of the brain regions examined the highest kynurenine aminotransferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activity.3. All samples from SHR showed greatly reduced kynurenine aminotransferase activity compared to WKY. These reductions were most pronounced in the medulla and spinal cord, approximately 45–55%, and lowest in the cerebellum and olfactory bulbs, approximately 25–30%.4. The kynurenic acid content of the rostral and caudal medulla as well as the spinal cord was also significantly lower in SHR.5. These results suggest that there may be a deficiency in the kynurenic acid content and kynurenine aminotransferase activity in the SHR.6. Given the accumulating evidence of the importance of medullary glutamatergic pathways in the control of blood pressure, as well as the higher sensitivity of cardiovascular neurons of SHR to applied glutamate, it seems possible that endogenous kynurenic acid in the brain may play a role in the control of blood pressure and the pathogenesis of experimental hypertension in the SHR.
COMPARISON OF SALT SENSITIVITY OF MALE AND FEMALE F2 PROGENY FROM CROSSES BETWEEN WHY AND SHRSP RATS
Authors: Nara Yasuo , Ikeda Katsumi , Nabika Toru , Sawamura Makoto , Mano Masayuki , Endo Jiro , Yamori Yukio 
Published: June 2007

SUMMARY1. The present study compared the salt sensitivity of male and female F2 progeny obtained from crosses between Wistar‐Kyoto/Izumo rats and stroke‐prone spontaneously hypertensive rats (SHRSP A3b/ Izm) after salt loading for 7 months.2. Average systolic blood pressure in male F2 progeny was 10 mmHg higher than that of female F2 progeny at 5 months without salt loading.3. The blood pressure in male F2 progeny was raised significantly 2 months after salt loading, but there was no further significant change in blood pressure even though salt loading was continued for 5 months.4. In female F2 progeny, however, a significant change in systolic blood pressure was observed 1 month after salt loading and there was a further significant rise in blood pressure over 6 months.5. Angiotensin I‐converting enzyme and RR 1023 loci were strongly linked to systolic and diastolic blood pressures in the male but not the female F2 progeny after salt loading for 7 months.6. We therefore speculate that the hormonal difference between sexes might influence salt sensitivity in the SHRSP.
GENES OF STRESS IN EXPERIMENTAL HYPERTENSION
Authors: Hamet P. , Sun Y. L. , Malo D. , Kong D. , Křen V. , Pravenec M. , Kuneš J. , Dumas P. , Richard L. , Gagnon F. , Tremblay J. 
Published: June 2007

SUMMARY1. A significant portion of blood pressure variance is modified by the environment.2. The present report summarizes evidence that: (i) the environmental response is genetically determined; (ii) various stressors can evoke a differential response in hypertensive animals and constitute its intermediate phenotypes; (iii) the response to heat stress can be assigned to a single ‘thermosensitivity’ locus; (iv) candidate genes of susceptibility to environmental stresses are member(s) of the heat stress gene (HSP) gene families; (v) a restriction fragment length polymorphism ofhsp70 and a single base mutation in the 3′‐untranslated region of hsp27 are associated with hypertension in recombinant inbred strains.3. In conclusion, HSP gene variants may be causative in susceptibility to hypertension.
MOLECULAR GENETICS OF THE SA GENE
Authors: Iwai Naoharu , Inagami Tadashi , Kinoshita Masahiko 
Published: June 2007

SUMMARY1. We have recently identified a candidate gene for rat genetic hypertension, termed Sa, by identifying an mRN A species that shows markedly higher expression in the kidneys of spontaneously hypertensive rats (SHR) than in those of Wistar‐Kyoto rats (WKY).2. Subsequent genetic co‐segregation analyses by ourselves and others indicated that the Sa gene locus did indeed influence blood pressure. Moreover, in a preliminary association study, we found an association of a polymorphism of the human Sa gene with essential hypertension.3. Further studies to identify functions of the Sa gene products are required before reaching a definite conclusion.
FREQUENCIES OF VARIANTS OF CANDIDATE GENES IN DIFFERENT AGE GROUPS OF HYPERTENSIVES
Authors: Zee Robert Y. L. , Bennett Craig L. , Schrader Andrew P. , Morris Brian J. 
Published: June 2007

SUMMARY1. In severe, familial hypertension, we have reported that the proportion of patients homozygous for the deletion allele of an insertion/deletion polymorphism of the angiotensin I‐converting enzyme gene is markedly decreased in older age groups, suggesting that this genotype is associated with increased risk of premature death. The aim of the present study was to examine the relationship with age, of variants of other genes that encode proteins having an influence on the cardiovascular system.2. Genotypes of 13 different variants at 12 relevant genetic loci were determined by either Southern blotting, followed by hybridization probing, or polymerase chain reaction techniques, as appropriate, using genomic DNA extracted from blood leukocytes. Genotype numbers were then assigned to the age categories of < 50, 50–59 and ≥60 years.3. Polymorphisms at the atrial natriuretic factor, antithrombin III, renin, angiotensinogen, neuropeptide‐Y Y1 receptor, insulin, α2‐adrenoceptor, β1‐adrenoceptor, growth hormone, low density lipoprotein receptor, insulin receptor and renal kallikrein gene loci were found to display similar allele frequencies in each age group of hypertensives, as well as in normotensive controls.4. In conclusion, we were unable to detect any difference with age for a range of variants of genes whose products have cardiovascular significance, suggesting that, like most polymorphisms, they carry no selective survival advantage or disadvantage in the hypertensive and normotensive population groups studied.
LYSOSOMAL IRON ACCUMULATION AND TUBULAR DAMAGE IN RAT PUROMYCIN NEPHROSIS AND AGEING
Authors: Harris David C. H. , Tay Ching , Nankivell Brian J. 
Published: June 2007

SUMMARY1. Energy dispersive X‐ray spectrometry was used to examine the relationship between proteinuria and increased urinary iron excretion, and structural and functional damage in puromycin nephrosis.2. After 11–12 days rats treated with puromycin (10 mg/100g, i.v.i.) had greater proteinuria (211.6 ± 35.7 mg/day, mean ± s.e.m.) and urinary iron excretion (15.4 ± 2.2 μg/day) than salinetreated controls (14.5 ± 1.4 mg/day and 1.1 ± 0.2 μg/day, respectively, both P<0.001).3. On day 13, mean lysosomal iron concentration of proximal tubular cells (306.6 ± 64.5 vs 11.9 ± 8.6 mg%, P<0.001), and proximal tubular cell damage assessed semi‐quantitively (1.17 ± 0.10 vs 0.62 ± 0.10, P<0.001) were higher and creatinine clearance (0.15 ± 0.01 vs 0.29 ± 0.02 mL/min perg kidney weight, P<0.001) lower than in control rats.4. At days 35, 60 and 360 there were no differences in any of the measured parameters between rats treated with puromycin or saline, and in both groups proteinuria, tissue damage and lysosomal iron concentration increased with time.5. Lysosomal iron accumulation was the only independent predictor of both functional and structural damage.6. In conclusion, the apparent association between proteinuria and tubulo‐interstitial damage in puromycin nephrosis, and with ageing, is best explained by factors associated with accumulation of iron within lysosomes of proximal tubule cells.
TRANSPLANTATION STUDIES OF THE ROLE OF THE KIDNEY IN LONG‐TERM BLOOD PRESSURE REDUCTION FOLLOWING BRIEF ACE INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Harrap Stephen B. , Wang Bao‐Zhong , MacLellan Donald G. 
Published: June 2007

SUMMARY1. Brief treatment with angiotensin‐converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure associated with a relatively selective reduction in renal vascular resistance.2. To study the possible role of the kidney in this long‐term hypotensive effect, we transplanted kidneys from untreated SHR into SHR that had been treated with perindopril (3 mg/kg per day) between 6 and 10 weeks of age and also transplanted kidneys from perindopril‐pretreated SHR into untreated SHR. After transplantation, the remaining native kidney was removed so that only donor kidneys remained.3. Untreated SHR that received kidneys from perindopril‐pretreated SHR showed an initial fall in blood pressure followed by a rapid increase in pressure, weight loss and early death.4. The transplantation of kidneys from control SHR into perindopril‐pretreated SHR resulted in a rise in blood pressure that obviated the long‐term reduction seen normally in these animals.5. Kidneys from perindopril‐pretreated SHR may be susceptible to the high blood pressure in untreated SHR.6. The blood pressure increase in perindopril‐pretreated SHR that accompanies substitution of the native kidneys by kidneys from untreated SHR further supports the hypothesis that the kidney is responsible for the long‐term pressure effects following ACE inhibition in young SHR.
EFFECT OF TRANSFORMING GROWTH FACTOR‐β1 ON PLATELET‐DERIVED GROWTH FACTOR RECEPTOR BINDING AND GENE EXPRESSION IN VASCULAR SMOOTH MUSCLE CELLS FROM SHR AND WKY RATS
Authors: Agrotis Alex , Saltis John , Bobik Alex 
Published: June 2007

SUMMARY1. This study examined the effects of transforming growth factor‐βl (TGF‐β1) on platelet‐derived growth factor‐BB (PDGF‐BB)‐stimulated DNA synthesis, [125I]‐PDGF‐BB receptor binding and PDGF‐β receptor mRNA expression in vascular smooth muscle cells (VSMC) isolated from Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).2. TGF‐β1 inhibited by 40% DNA synthesis stimulated by PDGF‐BB in VSMC from WKY rats but potentiated by 20% growth factor‐stimulated DNA synthesis in VSMC from the SHR.3. Since the difference in effect of TGF‐β1 could not be attributed to differential regulation of [125I]‐PDGF‐BB binding activity and PDGF‐β receptor mRNA expression, it is suggested that alterations in intracellular signalling pathways may account for the differential effects of TGF‐β1 on PDGF‐BB‐stimulated DNA synthesis in VSMC from SHR and WKY rats.
AUGMENTATION OF BARORECEPTOR REFLEX FUNCTION BY ORAL CALCIUM SUPPLEMENTATION IN ESSENTIAL HYPERTENSION
Authors: Dazai Yasunobu , Iwata Takeru , Hiwada Kunio 
Published: June 2007

SUMMARY1. We studied the effect of oral calcium supplementation (1.0 g/day) for 1 week on baroreceptor reflex function and the lability of blood pressure in association with the changes in autonomic nervous activity in 14 hospitalized patients with mild to moderate essential hypertension (nine males and five females, mean age of 56 ± 11.2 (s.d.) years).2. Baroreceptor reflex sensitivity (BRS) was determined by the change in R‐R intervals in response to the pressor response induced by phenylephrine injection. We measured coefficient of variation of R‐R interval (CVr‐r) and urinary excretion of catecholamines to evaluate the mechanism of change in BRS. We also used coefficient of variation of blood pressure (CVBP) and error of single cosinor analysis as parameters for lability of 24‐h blood pressure.3. The means of 24‐h systolic and diastolic blood pressures showed no significant changes after calcium supplementation for 1 week. BRS and CVR‐R were significantly increased by calcium supplementation. Daily excretions of norepinephrine and epinephrine corrected by creatinine were unchanged. Both CVbp and error of 24‐h systolic blood pressure showed a significant decrease after calcium treatment.4. These results indicate that oral calcium supplementation augments baroreceptor reflex function, in part through an enhancement of parasympathetic nervous activity, resulting in reduction of the lability of blood pressure in patients with mild to moderate essential hypertension.
INTERACTIONS BETWEEN 5‐HYDROXYTRYPTAMINE, NORADRENALINE AND THE THROMBOXANE‐A2 MIMETIC U44069 IN THE MARMOSET ISOLATED AORTA
Authors: Dyer S. M. , Bexis S. , Mano M. T. , de la Lande I. S. , Frewin D. B. , Head R. J. 
Published: June 2007

SUMMARY1. The effects of 5‐hydroxytryptamine (5‐HT) in the absence and presence of noradrenaline (NA) or the thromboxane‐A2 mimetic, U44069, were investigated in ring preparations of marmoset aorta.2. 5‐HT (0.001‐10 μmol/L) produced little or no contractile response in preparations at basal tone. When the tone was elevated to 50% of maximum with NA the predominant response to 5‐HT was relaxation. The 5‐HT2 receptor antagonist LY53857 (0.1 μmol/L) unmasked a contractile response to low concentrations of 5‐HT (0.01 ‐ 1.0 μmol/L) and reduced relaxation to high concentrations of 5‐HT (1.0‐10 μmol/L) in vessels precontracted with NA.3. In U44069‐contracted vessels, 5‐HT was contractile in the range 0.01‐1 μmol/L and relaxant in concentrations of 6.0‐10.0 μmol/L. Ketanserin (1.0 μmol/L) had no effect on the contraction or relaxation to 5‐HT.4. The relaxant response to 5‐HT was not significantly diminished in endothelium‐impaired arteries.5. In conclusion, 5‐HT exerts complex inhibitory and excitatory actions on the marmoset aorta. The inhibitory actions are not endothelium‐dependent and the excitatory actions do not appear to involve the 5‐HT2 receptor.
RENAL EXTRACTION OF ATRIAL NATRIURETIC PEPTIDE IN UNILATERAL RENAL ARTERY STENOSIS
Authors: Tunny Terry J. , Gordon Richard D. , Klemm Shelley A. , Stowasser Michael , Finn Wendy L. 
Published: June 2007

SUMMARY1. Elevated peripheral atrial natriuretic peptide (ANP) levels were observed in 12 patients with unilateral renal artery stenosis (U‐RAS).2. Renal extraction of ANP was higher across the affected than the unaffected kidney in U‐RAS, provided the glomerular filtration rate in the affected kidney was not severely reduced (> 12 mL/min). As ANP is a high clearance compound, reduced flow on the affected side may result in increased renal extraction of ANP.3. When glomerular filtration rate (GFR) in the affected kidney was severely reduced (<12 mL/min), renal extraction of ANP was also reduced, possibly contributing to increased circulating ANP levels in this subgroup.4. Overall, renal extraction of ANP was inversely correlated to peripheral ANP levels in patients with U‐RAS. This might be explained by progressive sodium retention as GFR falls leading to volume expansion and increased ANP secretion.
AN ASSOCIATION OF PRIMARY ALDOSTERONISM AND ADRENALINE‐SECRETING PHAEOCHROMOCYTOMA
Authors: Gordon Richard D. , Bachmann Anthony W. , Klemm Shelley A. , Tunny Terry J. , Stowasser Michael , Storie William J. , Rutherford John C. 
Published: June 2007

SUMMARY1. Two patients with adrenaline‐only secreting phaeochromocytomas and primary aldosteronism were studied.2. Urinary adrenaline levels were raised and plasma adrenaline was not suppressed normally following administration of clonidine. Plasma aldosterone to plasma renin activity ratios were repeatedly elevated.3. Both had large intra‐adrenal phaeochromocytomas visible on computerized tomography (CT) scanning. Surrounding adrenal cortical tissue contained an adenoma in one and nodular hyperplasia in the other.4. Following removal of the adrenal gland containing the phaeochromocytoma, plasma and urinary adrenaline levels, and plasma aldosterone to plasma renin activity ratios returned to normal.5. Adrenaline‐only secreting phaeochromocytomas and primary aldosteronism have been rarely diagnosed even as separate entities, but reliable screening tests are now available.6. Simultaneous presence of these two conditions of hormone excess is probably a chance occurrence. Alternatively, there may be a genetic predisposition to endocrine dysplasia, or an interaction between the contiguous medullary and cortical tissues, particularly after the normal architecture has been disturbed by an enlarging phaeochromocytoma.