bluuebunny/crossref_metadata_2025_split huggingface dataset:
SHEEP HYPOTHALAMUS CONTAINS A NON‐ANGIOTENSIN LIGAND FOR TYPE 1 AND TYPE 2 ANGIOTENSIN II RECEPTORS
Authors: Blasioli Julie , Kladis Athena , Clarke Iain J. , Campbell Duncan J. 
Published: June 2007

SUMMARY1. The aim of this study was to determine whether the brain contains an alternative ligand for angiotensin II (AII) receptors.2. A radioreceptor assay based upon bovine cerebellar membranes (Type 2 AII receptors) was used to monitor the partial purification of an AII‐like material from sheep hypothalami.3. This material displaces 125I‐[Sar1, Ala8I‐AII from both type 1 (rat adrenal capsuIar membranes) and Type 2 AII receptors in a manner parallel to that of AIL It has a size of ∼30000 Da, is strongly cationic, is stable to boiling but is destroyed by trypsin. It is not recognized by AII antisera.4. These data provide direct evidence for a non‐angiotensin endogenous ligand for brain AII receptors. This novel ligand may play a role in the regulation of blood pressure and other actions mediated by brain AII receptors.
DEMONSTRATION OF DEFECTIVE GLUCOSE UPTAKE AND STORAGE IN ERYTHROCYTES FROM NON‐INSULIN DEPENDENT DIABETIC PATIENTS AND EFFECTS OF METFORMIN
Authors: Yoa René G. , Rapin Jean R. , Wiernsperger Nicolas F. , Martinand Albert , Belleville Ivan 
Published: June 2007

SUMMARY1. Red blood cells can store glucose and may thus participate in blood glucose homeostasis. We investigated if a defect in this process exists in non‐insulin dependent diabetes (NIDD).2. Blood was obtained in fasting conditions from 10 normal and 10 newly diagnosed NIDD patients (before and after 4 weeks Metformin therapy). Washed erythrocytes were resuspended in media containing various glucose concentrations (4.4, 6.6, 8.8 and 13.2 mmol/L). Total glucose uptake was calculated as the sum of the measurements of lactate as well as free glucose, the latter being determined before and after addition of amyloglucosidase to the pellet.3. Cells from diabetics showed a pronounced reduction in glucose uptake, particularly in their capacity to store glucose as glycogen (reactive to amyloglucosidase). Metformin treatment almost normalized glycogen levels, whereas lactate declined concomitantly in the pellet.4. Our data demonstrate that a defect in glucose uptake exists in erythrocytes from NIDD patients, affecting both free and stored glucose, and that this defect is reversed by Metformin treatment, indicating that this drug can increase glycogen levels even in insulin‐insensitive cells.5. Thus, in view of their total mass, erythrocytes may be important in the impaired glucose homeostasis in NIDD, in particular in marked hyperglycaemia such as after a meal.
INTRALYMPHOCYTIC FREE CALCIUM AND MAGNESIUM IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND EFFECTS OF BLOOD PRESSURE AND VARIOUS ANTIHYPERTENSIVE AGENTS
Authors: Adachi Minoru , Nara Yasuo , Mano Masayuki , Ikeda Katumi , Horie Ryoichi , Yamori Yukio 
Published: June 2007

SUMMARY1. Free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured in peripheral lymphocytes from stroke‐prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar‐Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents‐treated SHRSP, and from secondary hypertensive WKY.2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i.3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin‐converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i.4. After 40‐day administration of NG‐nitro‐l‐arginine (l‐NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the l‐NNA treated and non‐treated groups.5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of divalent cation handling.
PHARMACOLOGICAL ACTIONS OF THE COENZYMES NAD(H) AND NADP(H) ON THE RAT ANOCOCCYGEUS MUSCLE
Authors: Najbar A. , Li C. G. , Rand M. J. 
Published: June 2007

SUMMARY1. The pharmacological actions of the oxidized and reduced forms of nicotinamide‐adenosine dinucleotide (NAD, NADH) and nicotinamide‐adenosine dinucleotide phosphate (NADP, NADPH) were studied on rat isolated anococcygeus muscles.2. The actions of the two nucleotides were different, but there were no apparent qualitative differences between the oxidized and reduced forms of each.3. In fully relaxed anococcygeus muscles, NADP(H) produced transient contractions that were subject to desensitization, but NAD(H) had no effect.4. NADP(H) slightly enhanced contractions elicited by noradrenergic nerve stimulation. In contrast, noradrenergic contractions were inhibited by NAD(H). NADH reduced the stimulation‐induced release of noradrenaline, but enhanced contractions elicited by exogenous noradrenaline.5. In anococcygeus muscles partly contracted with guanethidine, NAD(H) produced a further sustained increase in tone; in contrast, NADP(H) mainly produced transient relaxations to which there was immediate desensitization.6. Relaxations of anococcygeus muscle elicited by nitrergic nerve stimulation were not affected by NAD. In contrast, NADP(H) reduced them.7. The actions of NAD(H) were generally the same as those of adenosine and can be attributed to activation of P1‐purinoceptors since they were blocked by the selective antagonist 8‐sulphophenyl‐theophylline.8. The actions of NADP resembled those of the P2‐purinoceptor agonist ATP to some extent, but there were some differences. As suggested by others, NADP may act on a unique receptor.
THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX
Authors: Kingwell Bronwyn A. , Krause Lisa , Julius Stevo 
Published: June 2007

SUMMARY1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure‐heart rate reflex (MAP‐HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation.2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention.3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced.4. The maximum gain of the MAP‐HR reflex, studied using the ‘steady‐state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β‐adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period.5. The MAP‐HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.
HYPOTHESIS: CYTOTOXIC LYMPHOCYTE GRANULE SERINE PROTEASES ACTIVATE TARGET CELL ENDONUCLEASES TO TRIGGER APOPTOSIS
Authors: Smyth Mark J. , Browne Kylie A. , Thia Kevin Y. T. , Apostolidis Vicki A. , Kershaw Michael H. , Trapani Joseph A. 
Published: June 2007

SUMMARYUpon interaction with target cells, cytotoxic T lymphocytes and natural killer cells vectorially secrete highly specialized cytoplasmic granules containing perforin and a family of serine proteases (granzymes). This granule exocytosis mechanism of cytolysis is of patho‐physiological importance, and usually results in target cell DNA fragmentation. Neither perforin nor granzymes possess inherent nuclease activity, but in combination they can induce target cell apoptosis. Perforin forms transmembrane pores in the target cell, thereby enabling granzymes to access target cell substrates. The target cell substrates of granzymes are unknown, but granzyme A binding and cleavage of the nuclear shuttle protein nucleolin in target cells demonstrates that granzymes may act on nuclear substrates. Furthermore, the presence of granzyme B and other granzyme activities in the nucleus of cytotoxic lymphocytes indicates that granzymes can be transported from the cytoplasm to the nucleus.It is hypothesized that perforin enables effector granzymes to enter the target cell cytoplasm and following their transport into the nucleus, granzymes cleave specific target cell nuclear proteins to activate autolytic endonucleases that fragment DNA. In cytotoxic effectors, these nuclear substrates are normally protected from granzymes by endogenous inhibitors.
AUGMENTATION OF ANGIOTENSIN II RELEASE FROM ISOLATED MESENTERIC ARTERIES OF WISTAR‐KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING NEPHRECTOMY
Authors: Shi Shang‐Jin , Rakugi Hiromi , Higashimori Koichi , Higaki Jitsuo , Mikami Hiroshi , Ogihara Toshio 
Published: June 2007

SUMMARY1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time‐dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII).2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy.3. The mesenteric arteries from kidney‐intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney‐intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy.4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR.5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.
CONTROL OF CORONARY BLOOD FLOW BY ENDOTHELIAL RELEASE OF NITRIC OXIDE
Authors: Losano G. , Pagliaro P. , Gattullo Donatella , Marsh N. A. 
Published: June 2007

SUMMARY1. Nitric oxide (NO) is released from vascular endothelium following conversion of l‐arginine to l‐citrulline by calcium‐calmodulin‐dependent ‘constitutive’ NO‐synthase.2. Nitric oxide release occurs under basal conditions, in response to chemical stimuli (acetylcholine, bradykinin, thrombin, prostacyclin, serotonin, etc.) and in response to changes in shear stress (effects of blood velocity on vascular endothelium).3. Analogues of l‐arginine inhibit NO and are widely used to study the effects of NO on the cardiovascular system: in intact animals, these inhibitors cause vasoconstriction, leading to an increase in arterial blood pressure (ABP) and bradycardia.4. Bradycardia induced by NO inhibitors is due, in part, to baroreceptor activity following the increase in ABP and in part to a direct effect on the sino‐atrial node.5. In the intact animals and isolated perfused heart, NO inhibitors cause coronary vasoconstriction and hence a reduction in basal coronary flow. This effect, however, is not seen in isolated coronary vessels.6. From experiments in which ABP did not change, NO does not appear to have an important role in regulating coronary vasomotor tone under basal conditions.7. Nitric oxide appears to be involved in the duration of reactive hyperaemia following coronary vascular occlusion but is not involved to any significant extent in the peak amplitude of hyperaemia.8. Responses to vasodilator stimuli which do not involve NO in the initiation of the vasodilation may be prolonged by the effect of increased blood flow (shear stress) which releases NO and potentiates hyperaemia.
FISH PROTEIN‐RICH DIET ATTENUATES HYPERTENSION INDUCED BY DIETARY Ng‐NITRO‐L‐ARGININE IN NORMOTENSIVE WISTAR‐KYOTO RATS
Authors: Jr O. G. Gutierrez , Ikeda K. , Nara Y. , Deguan G. U. , Yamori Y. 
Published: June 2007

SUMMARY1. Dietary 0.023%NG‐nitro‐L‐arginine (L‐NNA), an inhibitor of nitric oxide synthesis, induced hypertension in normotensive Wistar‐Kyoto rats (WKY). This hypertension was significantly attenuated in WKY given a fish protein‐rich diet.2. The supplement of 2% L‐arginine given in a standard diet or a diet containing 3% taurine for drinking did not significantly affect the development of hypertension induced by L‐NNA in WKY.3. WKY which received the standard diet mixed with 10% urea and 0.023% L‐NNA had significantly attenuated hypertension compared with WKY receiving the standard diet mixed with 10% kaolin and 0.023% L‐NNA.4. These results suggest that the attenuation of hypertension in L‐NNA‐treated WKY rats given a fish protein rich diet may be partly caused by urea, a metabolic end‐product of protein.
SIMILARITY OF BLOOD PRESSURE FOR EACH GENOTYPE OF THE INSERTION/DELETION POLYMORPHISM OF THE DIPEPTIDYL CARBOXYPEPTIDASE‐1 GENE IN DIFFERENT AGE GROUPS OF PATIENTS WITH SEVERE, FAMILIAL ESSENTIAL HYPERTENSION
Authors: Morris Brian J. , Zee Robert Y. L. 
Published: June 2007

SUMMARY1. The association of alleles of an insertion/deletion polymorphism (I/D) of the dipeptidyl carboxypeptidase‐1 gene with hypertension is controversial. If a particular allele makes a major contribution to blood pressure, then hypertensives homozygous for this allele could be expected to have higher high blood pressure than those homozygous for the alternate allele.2. The present study examined this hypothesis by comparing pretreatment blood pressures of hypertensives who had been genotyped for the I/D polymorphism. Blood pressures for different age groups (< 50, 50–59 and ≥60 years) were also examined for each genotype. In addition, several other parameters were examined.3. Systolic blood pressures were found to be 167 ± 3, 167 ± 3 and 170 ± 6 mmHg (mean ± s.e.) for the genotypes II, ID and DD, respectively. Diastolic blood pressures were 113 ± 4, 111 ± 2 and 111 ± 4, for the respective genotypes. One‐way anova showed that the respective blood pressure values did not differ significantly across genotypes. Blood pressures for different age groups of hypertensives were also similar.4. In addition, body mass index, mean age and sex did not differ between genotypes, either for the group as a whole or for the different age groups.5. In conclusion, the present study could find no evidence to support a genetic association between the I/D polymorphism of DCP1 and blood pressure in a group with severe, familial hypertension living in Sydney.
MECHANISMS OF THE PRESSOR RESPONSE TO INTRAVENOUS THYROTROPIN‐RELEASING HORMONE IN THE RAT
Authors: Evequoz D. , Burnier M. , Niederberger M. , Brunner H. R. , Nussberger J. , Waeber B. 
Published: June 2007

SUMMARY1. The purpose of this study was to examine the contribution of the sympatho‐adrenomedullary system to the blood pressure response to an intravenous bolus of thyrotropin‐releasing hormone (TRH) in conscious medullectomized and sham‐operated rats.2. The peak pressor effect of 0.5 mg TRH was significantly increased in rats having no adrenal medulla (+ 24.2 ± 1.6 mmHg, mean ± s.e.m., P<0.01) as compared to sham‐operated animals (+12.2 ± 3.0 mmHg).3. Blockade of alpha‐adrenergic receptors with phentolamine abolished the pressor effect of TRH in control rats (+ 2.1 ± 1.9 mmHg) but did not attenuate the blood pressure response of medullectomized rats (+ 21.5 ± 4.7 mmHg). In contrast, beta‐blockade with propranolol blunted the blood pressure responsiveness of rats subjected to adrenal medullectomy (+ 12.4 ± 2.6 mmHg) but did not modify the effect of TRH in sham‐operated controls (+ 10.9 ± 2.9 mmHg).4. The direct in vitro effect of TRH on isolated mesenteric rat arteries was also evaluated. TRH did not induce contractions of isolated arteries.5. These results suggest that in rats with intact adrenals, the pressor effect of intravenous TRH is mediated primarily by a stimulation of alpha‐adrenergic receptors. Adrenal medullectomy appears to enhance the blood pressure response to intravenous TRH. Activation of cardiac beta‐adrenocep‐tors seems to contribute to the blood pressure increasing effect of intravenous TRH in medullectomized animals.
DEVELOPMENTALLY REGULATED TRANSFORMING GROWTH FACTOR‐β1 ACTION ON VASCULAR SMOOTH MUSCLE GROWTH IN THE SHR
Authors: Saltis John , Agrotis Alex , Kanellakis Peter , Bobik Alex 
Published: June 2007

SUMMARY1. This study examined the effects of transforming growth factor‐β11 (TGF‐β1) on platelet‐derived growth factor‐BB (PDGF‐BB)‐stimulated proliferation of vascular smooth muscle cells (VSMC) isolated from aortic tissue of I, 4 and 12 week old spontaneously hypertensive rats (SHR).2. In 1 week old SHR, TGF‐βl inhibited by about 60% VSMC proliferation stimulated by PDGF‐BB; this inhibitory action of TGF‐β1 was absent in VSMC isolated from 4 week old, prehypertensive SHR. In contrast, TGF‐β1 potentiated by about 125% the mitogenic activity of PDGF‐BB in VSMC cultures from adult SHR.3. Age‐dependent alterations in the action of TGF‐β1 suggests an important role for TGF‐β1 in the development of vascular hypertrophy from adolescence onwards in the SHR.
EFFECT OF FLUMAZENIL ON BASAL AND NALOXONE‐STIMULATED ACTH AND CORTISOL RELEASE IN HUMANS
Authors: Torpy David J. , Jackson Richard V. , Grice Jeffrey E. , Hockings Gregory I. , Crosbie Georgina V. , Walters Margaret M. 
Published: June 2007

SUMMARY1. Endogenous benzodiazepine receptor ligands are thought to influence the human hypo‐thalamic‐pituitary‐adrenal (HPA) axis and naloxone, a known stimulator of adrenocorticotropic hormone (ACTH) release, is thought to act via release of hypothalamic corticotropin‐releasing hormone.2. The aim of the present study was to assess the influence of endogenous benzodiazepine‐receptor ligands by administering flumazenil (Ro 15–1788), a benzodiazepine antagonist, and measuring ACTH and cortisol release, both basal and during naloxone‐stimulation.3. Nine normal volunteers in a placebo‐controlled double‐blind design were studied. Flumazenil (0.5 mg, i.v. bolus) was given 2 min before naloxone (125 μg/kg bodyweight, i.v. bolus) immunoreactive‐adrenocorticotropic hormone (IR‐ACTH) and cortisol levels were measured at frequent intervals from 60 min before to 120 min after naloxone injection.4. Flumazenil had no effect on ACTH and cortisol release when given alone; flumazenil area under the ACTH/time curve (pmol/L.min) = ‐36.5 ± 63.5 compared with placebo = ‐ 53.5± 31.8, flumazenil area under the cortisol/time curve (nmol/L.min x 10−3) = ‐ 2.4 ± 2.4 compared with placebo ‐ 0.56 ± 1.4. Flumazenil did not change the ACTH and cortisol release achieved with naloxone; naloxone area under the ACTH/time curve (pmol/L. min) = 327.8 ± 61.7 compared with flumazenil/naloxone = 366.3 ± 88.1, naloxone area under the cortisol/time curve (nmol/L.minX 10−3) = 12.2 ± 3.4 compared with naloxone/flumazenil = 10.5±2.1.5. The authors conclude that flumazenil does not modify basal or stimulated ACTH and cortisol release in healthy humans. This would suggest that endogenous benzodiazepine‐like ligands and the benzodiazepine/gamma‐aminobutyric acid receptor complex do not tonically influence the hypothalamic‐pituitary‐adrenal axis.
EFFECT OF TEMOCAPRIL ON HAEMODYNAMIC AND HUMORAL RESPONSES TO EXERCISE IN PATIENTS WITH MILD ESSENTIAL HYPERTENSION
Authors: Arita Mikio , Ueno Yuji , Nakamura Chigusa , Akitsu Toshio , Nakamura Yoshinari , Wanaka Yoshio , Nishio Ichiro , Masuyama Yoshiaki 
Published: June 2007

SUMMARY1. This study was carried out to evaluate the effect of temocapril on haemodynamic and humoral responses to exercise in nine patients with mild essential hypertension (WHO stages I and II).2. After a 4‐week placebo period, temocapril was administered at a dose of 1.0 mg once daily for 2–4 weeks. Graded submaximal bicycle ergometer exercise was performed before and after temocapril treatment, and the changes in arterial blood pressure, heart rate, cardiac output (CO), and systemic vascular resistance (SVR) were evaluated. In addition, the plasma norepinephrine (NE) level was determined both at rest and peak exercise before and after temocapril treatment.3. Both the systolic and diastolic blood pressure were reduced at rest and during exercise by temocapril treatment. No significant change in the resting heart rate and CO was observed, and the exercise‐induced increase of these parameters was also not affected by temocapril. In contrast, the resting SVR was significantly decreased by temocapril, although the exercise SVR was similar during both temocapril and placebo treatment.4. Although there was no significant change in the plasma NE level with temocapril treatment, the exercise‐induced increase of plasma NE was significantly suppressed by temocapril.5. These results indicate that temocapril reduces the blood pressure without causing any significant changes in the heart rate and CO at rest, and that it does not produce any changes in the haemodynamic response to exercise.
RENIN AND ANGIOTENSIN‐CONVERTING ENZYME GENOTYPES IN PATIENTS WITH ESSENTIAL HYPERTENSION AND LEFT VENTRICULAR HYPERTROPHY
Authors: West M. J. , Summers K. M. , Burstow D. J. , Wong K. K. , Huggard P. R. 
Published: June 2007

SUMMARY1. The associations between left ventricular hypertrophy (LVH) and specific alleles of the renin and angiotensin‐converting enzyme (ACE) genes were studied in patients with essential hypertension and normal blood pressure.2. LVH was present in 42% of those with essential hypertension (n= 72) and 17% of those with normal blood pressure (n= 44).3. The frequency of each renin allele was the same in hypertensive and in normotensive patients. Renin allele frequencies were also the same for those with LVH and those with normal cardiac mass. When only hypertensives were considered, renin alleles were in the same proportion for the groups with and without LVH. Similarly, ACE alleles were not associated with essential hypertension nor with elevated cardiac mass.4. We conclude that, in this population, variations in the renin or ACE genes do not contribute significantly to the development of LVH or to essential hypertension.