bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPARATIVE STUDY ON α1‐ADRENOCEPTOR ANTAGONIST BINDING IN HUMAN PROSTATE AND AORTA
Authors: Yamada Shizuo , Suzuki Mayumi , Tanaka Chiaki , Mori Ryutaro , Kimura Ryohei , Inagaki Osamu , Honda Kazuo , Asano Masaharu , Takenaka Toichi , Kawabe Kazuki 
Published: June 2007

SUMMARY1. Specific binding of [3H]‐prazosin in prostatic and aortic membranes of humans was saturable and of high affinity (prostate: apparent dissociation constant, Kd= 0.35 ± 0.03 nmol/L; aorta: Kd= 0.26 ± 0.03 nmol/L). The density of [3H]‐prazosin binding sites (Bmax) for prostate and aorta was 546 ± 31 and 61.6 ± 1.6 fmol/mg protein, respectively.2. Prazosin, YM617, naftopidil and urapidil competed with [3H]‐prazosin for the binding sites in a dose‐dependent manner in the prostate and aorta of humans. The binding affinities of these antagonists in both tissues were compared, based on the inhibition constant, Ki. Both prazosin and urapidil showed similar affinity to [3H]‐prazosin binding sites in human tissue, whereas YM617 and naftopidil showed approximately a 12 and two times higher affinity, respectively, to α1‐adrenoceptor sites of prostate than aorta.3. The chloroethylclonidine treatment reduced partially the Bmax values for specific [3H]‐prazosin binding in the prostate and aorta of humans with little effect on the Kd values.4. These data suggest that YM617 is a relatively selective antagonist of human prostatic α1‐adrenoceptors.
WEB‐2086 AND INDOMETHACIN DO NOT MODIFY BLOOD PRESSURE FALL ON UNCLIPPING HYPERTENSIVE RATS
Authors: Smith Anthony J. , Gerkens John F. , Dosen Peter 
Published: June 2007

SUMMARY1. Pretreatment with intravenous WEB‐2086 (0.5 mg/ kg; an antagonist of the actions of platelet activating factor; PAF) with or without indomethacin (2 mg/ kg) failed to prevent or modify the fall in blood pressure following unclipping of the renal artery of anaesthetized two‐kidney, one‐clip hypertensive rats.2. The same medications given to two other groups of rats 60 min after unclipping when the blood pressure had fallen to stable levels failed to reverse the fall.3. Despite evidence that both prostanoids and PAF can be detected in increased amounts in renal venous blood after unclipping, they do not appear to mediate the reduction in blood pressure in this model of reversible hypertension.
INHIBITORY EFFECTS OF VERAPAMIL ON [3H]‐ACETYLCHOLINE RELEASE IN THE CENTRAL NERVOUS SYSTEM OF SPRAGUE‐DAWLEY RATS
Authors: Tsuda Kazushi , Tsuda Seiko , Goldstein Menek , Masuyama Yoshiaki 
Published: June 2007

SUMMARY1. The purpose of the present study was to investigate the effects of verapamil, a Ca2+ channel blocker, on acetylcholine (ACh) release in the CNS.2. Striatal slices of rats, prelabelled with [3H]‐ACh, were superfused with Krebs'‐Ringer solution. The slices were stimulated by electrical pulses (1 Hz) or by an excitatory amino acid, l‐glutamate and the effects of verapamil on the release of ACh were examined.3. Electrical stimulation produced an increase in [3H]‐ACh release from the striatal slices. Exposure of the slices to verapamil significantly inhibited the stimulation‐evoked [3H]‐ACh release.4. An endogenous excitatory amino acid, l‐glutamate, also elicted the release of [3H]‐ACh. Verapamil significantly reduced the l‐glutamate‐induced release of [3H]‐ACh and the inhibitory effect of verapamil was more pronounced in the presence of Mg2+ in the medium.5. The results of the present study demonstrate that verapamil inhibited both electrically‐ and chemically‐stimulated [3H]‐ACh release from the rat striatum. The inhibition of cholinergic transmission by verapamil might be related to the central effect of the Ca2+ channel blocker.
HETEROGENOUS ACTIVITY OF BRL 35135, A β3‐ADRENOCEPTOR AGONIST, IN THERMOGENESIS AND INCREASED BLOOD FLOW IN BROWN ADIPOSE TISSUE IN ANAESTHETIZED RATS
Authors: Takahashi Hakuo , Nakamura Shohei , Shirahase Hiroaki , Yoshida Toshihide , Nishimura Masato , Yoshimura Manabu 
Published: June 2007

SUMMARY1. The effects of BRL 35135, a β3‐adrenergic agonist, on body temperature and regional blood flow in brown adipose tissue (BAT) were simultaneously recorded in anaesthetized rats and compared to isoproterenol.2. BRL 35135 at doses of 0.1 and 1 μg/kg (i.v.) induced dose‐dependent increases in BAT temperature with minimal effects on systemic diastolic blood pressure (DBP), heart rate (HR) and BAT blood flow.3. The thermogenic effect of BRL 35135 at a dose of 10 μg/kg (i.v.) was smaller than that at a dose of 1 μg/kg, and was accompanied by a marked increase in BAT blood flow.4. Isoproterenol at doses of 0.01–1 μg/kg (i.v.) dose‐dependently increased HR and BAT blood flow and decreased DBP. It did not affect BAT temperature.5. These findings indicate that unlike isoproterenol, BRL 35135, at the lower doses, selectively causes thermogenesis in BAT which was detectable as changes in BAT temperature, and that the vasodilator effect in BAT is not as sensitive as the thermogenic effect of β3‐adrenergic agonists.
BLOOD VOLUME MEASUREMENTS IN THE NEONATAL LAMB: VALIDATION OF A METHOD USING [51Cr]‐LABELLED RED CELLS
Authors: Moritz Karen M. , Potocnik Simon J. , Tangalakis Kathy , Wintour E. Marelyn 
Published: June 2007

SUMMARY1. The reproducibility of blood volume measurements, using [51Cr]‐labelled red blood cells (RBC) was tested in three lambs, 79–89 days of age, and the accuracy was tested in eight lambs, 83± 0.4 days of age, in which blood volume was measured simultaneously by [51Cr]‐RBC and [125I]‐gamma globulin plus haematocrit (hct).2. The blood volumes (mean ± s.e.) of the three lambs, on four occasions, were 64.5± 2.5, 68.8 ± 2.9 and 63.9 ± 3.7 mL/kg, respectively, and the coefficients of variation were 7.8, 8.6 and 11.6%, respectively.3. The mean blood volume of eight lambs was 60.9 ± 3.3 mL/kg by [51Cr]‐RBC, and 60.8 ± 2.4 mL/ kg from plasma volume and hct. These were not statistically different.4. Arterial hct was 31.2 ± 0.5%, which was not statistically different from the whole body hct of 31.2 ±2.6%.5. It is concluded that [51Cr]‐RBC can be used to measure accurate and reproducible blood volumes in lambs.
LOW CHOLESTEROL AND IMPAIRED CARDIAC FUNCTION FOLLOWING HEART TRANSPLANTATION
Authors: Kaye David M. , Johnston Leonie , Dart Anthony M. 
Published: June 2007

SUMMARY1. During follow‐up of 59 cardiac transplant recipients over 2 or more years, a small group of subjects was observed who displayed an unpredictable, relatively marked, reduction in plasma cholesterol.2. A significant proportion of these subjects were subsequently observed as having experienced a marked decline in left ventricular function at the time of routine radionuclide ventriculography.3. While the mechanism for this fall in cholesterol is unclear, the observation of such an unexpected reduction in total cholesterol, late after heart transplantation should be considered significant and prompt further investigation including an assessment of allograft function.
CHOLESTERYL ESTER TRANSFER PROTEIN: ITS ROLE IN PLASMA LIPID TRANSPORT
Authors: Barter Philip , Rye Kerry‐Anne 
Published: June 2007

SUMMARY1. The cholesteryl ester transfer protein (CETP) is a hydrophobic glycoprotein which acts in plasma to redistribute cholesteryl esters and triglyceride between plasma lipoproteins.2. CETP also plays an important role in determining the composition and particle size distribution of high density lipoproteins (HDL).3. Activity of CETP may be regulated in four ways: By factors which influence the concentration of CETP in plasma; by the activity of CETP inhibitor proteins; by variations in the concentrations and compositions of donor and acceptor lipoproteins and by factors which influence the interaction of CETP with plasma lipoproteins.4. The mechanism of action of CETP is uncertain. Two models have been been proposed: (i) a shuttle model in which CETP physically transports lipids between lipoprotein particles and (ii) a ternary complex model in which CETP forms a bridge between two lipoprotein particles, enabling them to exchange lipids.5. Evidence is accumulating that CETP may be a pro‐atherogenic factor.
NO EFFECT OF KININS ON DNA SYNTHESIS IN LNCaP PROSTATE CANCER CELLS
Authors: Reid Joanna , Schrader Andrew P. , Morris Brian J. 
Published: June 2007

SUMMARY1. Prostate has kininogenase activity and expresses members of the tissue kallikrein gene family. The present study examined the effect of exogenous and endogenous kinins on growth of LNCaP prostate adenocarcinoma cells.2. Rate of DNA synthesis was measured by incorporation over 4 h of [3H]‐thymidine into a TCA insoluble fraction of LNCaP cells that had been cultured for 24 h.3. Increased [3H]‐thymidine incorporation was seen in response to 10 nmol/L testosterone (4– 103 ± 5 s.e.%), dihydrotestosterone (+ 113 ± 14%) and R 1881 (+64 ± 10%) (P± 0.001; n = 4).4. In contrast 0.05, 5 and 1000 nmol/L lysyl‐bradykinin had no effect (15 ± 4, 10 ± 9 and 5 ± 3 s.e.%, respectively; n = 7). Des‐Arg9[Leu8]‐bradykinin (a B1 receptor antagonist) and/or d‐Arg‐[Hyp3,Thi5,8,d‐Phe7]‐bradykinin (a B2 receptor antagonist), 1 nmol/L, and indomethacin, 5 μmol/L, also had little or no effect.5. In conclusion, kallidin and endogenous kinins and prostaglandins have little or no effect on DNA synthesis and therefore on the growth of LNCaP cells in comparison to the two‐fold stimulation produced by androgens.
DIFFERENCES IN ENDOTHELIUM‐DEPENDENT RELAXATION IN VARIOUS ARTERIES FROM WATANABE HERITABLE HYPERLIPIDAEMIC RABBITS WITH INCREASING AGE
Authors: Kitagawa Satomi , Yamaguchi Yu , Sameshima Emiko , Kunitomo Masaru 
Published: June 2007

SUMMARY1. Endothelium‐dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A 23187 was examined in aorta, coronary, basilar and renal arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls.2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with vasoconstrictors, endothelium‐dependent relaxation in response to ACh was attenuated with age compared to the heterozygous WHHL rabbits. A significant negative correlation was found between the total cholesterol content and the relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month old WHHL rabbits.3. In the rings of basilar arteries, endothelium‐dependent relaxations to ACh were not modified with age. Similarly, in the rings of renal arteries, the relaxation response to ACh was not changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at higher concentrations of ACh (10−7 to 10−6 mol/L). The contraction was endothelium‐dependent and inhibited by indomethacin.4. A 23187‐induced endothelium‐dependent relaxations were also markedly attenuated in the aorta and significantly in the coronary artery with age.5. Endothelium‐independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages.6. These findings indicate that in the aorta and coronary artery of the WHHL rabbit, the endothelium‐dependent relaxation to ACh and A 23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposition in the arterial wall) but is preserved in the basilar and renal artery.
EFFECTS OF PROLONGED (48 H) INFUSION OF CORTISOL ON BLOOD PRESSURE, RENAL FUNCTION AND FETAL FLUIDS IN THE IMMATURE OVINE FOETUS
Authors: Dodic Miodrag , Wintour E. Marelyn 
Published: June 2007

SUMMARY1. This study describes the effects of prolonged (48 h) infusion of cortisol into ovine foetuses (100–110 days of gestation: term is 150 days) at a time when endogenous plasma cortisol concentrations are <5 nmol/L.2. In four chronically cannulated foetuses (107 ± 0.9 day) the infusion of saline (0.9% NaCl; w: v 0.19 mL/h, 48 h) had no effect on blood pressure, renal function, or composition of amniotic and allantoic fluids.3. In six foetuses (107 ± 1 day) the infusion of cortisol (250 μg/h) increased plasma cortisol concentrations from 4.1 ± 0.7 to 118 ± 9 nmol/L (P < 0.001), increased mean arterial pressure from 34 ± 1 to 40 ± 1 mmHg (P < 0.001), increased glomerular filtration rate (P<0.05), urine flow rate, and free water clearance (P<0.01).4. There was a significant increase in excretion rates of potassium and creatinine as a result of cortisol infusion, but no natriuresis, indicating some functional maturation of the fetal kidney.5. Cortisol infusion had no effect on the volumes of amniotic and allantoic fluids; allantoic fluid composition was unchanged; significant decreases occurred in amniotic fluid osmolality, sodium and chloride concentrations, and in lung liquid osmolality, potassium, creatinine, magnesium, glucose and fructose concentrations.6. Thus prolonged exposure of the immature ovine foetus to elevated cortisol concentrations produced significant alterations in the water and electrolyte balance of the foetus.
CONTRASTING EFFECTS OF ISOPROTERENOL AND PHOSPHODIESTERASE I11 INHIBITOR ON INTRACELLULAR CALCIUM TRANSIENTS IN CARDIAC MYOCYTES FROM FAILING HEARTS
Authors: Honda Masaaki , Kuramochi Takehiko , Ishinaga Yuji , KUZUO Hiroshi , Tanaka Koichi , Morioka Shigefumi , Enornoto Koh‐Ichi , Takabatake Toshikazu 
Published: June 2007

SUMMARY1. Effects of a newly developed phosphodiesterase (PDE) I11 inhibitor, E‐1020, on intracellular calcium transients were compared with those of isoproterenol (ISO) in isolated single myocytes from failing hearts secondary to pulmonary hypertension induced by monocrotaline injection. Myocytes were isolated by enzyme digestion using a Langendorff apparatus. Changes in intracellular calcium concentrations ([Ca2+]i,) were recorded using a fura‐2 fluorescence microscopic technique. Cyclic AMP contents of the hearts were measured by radio‐immunoassay.2. Myocytes from failing hearts showed Ca2+ transients with a low peak (low amplitude) and delayed decline of Ca2+ transients. Both IS0 and E‐1020 increased peak [Ca2+]i, max +d[Ca2+]i/dt, and max − d[Ca2+]i/dt in a concentration‐dependent manner while both agents decreased T80L (time to 80% decline of amplitude from peak light). The concentrations which increased peak [Ca2+]i by 50% were 1.6 × 10‐9 mol/L of IS0 and 2× 10‐6 mol/L of E‐1020. These concentrations increased CAMP in the heart to the same levels. Analysis of the effects of both agents on peak [Ca2+], versus max ‐d[Ca2+]i/dt showed that IS0 is much more effective on peak [Ca2+], while E‐1020 is more effective on max ‐d[Ca2+]i,/dt.3. These results showed that the effects of I S 0 and E‐1020 on the parameters of intracellular Ca2+ transients of single myocytes from failing hearts are slightly different, and suggest that E‐1020 may improve diastolic function as well as systolic function in failing hearts.
CALCIUM TRANSIENTS IN SINGLE MYOCYTES AND MEMBRANOUS ULTRASTRUCTURES DURING THE DEVELOPMENT OF CARDIAC HYPERTROPHY AND HEART FAILURE IN RATS
Authors: Kuramochi Takehiko , Honda Masaaki , Tanaka Koichi , Enornoto Koh‐ichi , Hashimoto Michio , Morioka Shigefumi 
Published: June 2007

SUMMARY1. We examined changes in intracellular calcium transients of separated single myocytes from the right ventricle (RV) of the rat heart during the change from adaptation to maladaptation in response to a pressure overload.2. Right ventricular hypertrophy (RVH) secondary to pulmonary hypertension was induced by a subcutaneous injection of monocrotaline. Developed tensions of the RV‐free wall were decreased as RVH progressed. Single myocytes were separated from the RV during different stages of RVH. Fura‐2/AM‐loaded cells were field stimulated, and changes in calcium transients were measured by Olympus OSP‐3 system. We also examined membranous ultrastructures (sarcoplasmic reticulum, mitochondria, surface caveolae) involved in calcium metabolism in the hearts using scanning electron microscopy.3. We observed characteristic changes in calcium transients during the change from adaptation to maladaptation, and also found that one parameter (amplitude) of calcium transients appeared to be correlated with the changes in the number of sarcoplasmic reticulum.4. These results provided some insights into the mechanism of calcium handling of hypertrophied heart in response to a pressure overload from adaptation to maladaptation especially when stimulatory frequency was high, and suggested that heart rate control is a very important factor for the treatment of patients with congestive heart failure.
MECHANICAL DETERMINANTS OF MYOCARDIAL OXYGEN CONSUMPTION
Authors: Gibbs C. L. 
Published: June 2007

SUMMARY1. Recent developments which attempt to identify the mechanical determinants of myocardial oxygen consumption (mV̇o2) are considered, with emphasis being placed on the pressure‐work and pressure‐volume area (PVA) indices.2. The difficulty of establishing a realistic in vivo basal mV̇o2 value is explained and the experimental reasons for the controversy over the magnitude of the activation metabolism are outlined.3. The time varying elastance model of the heart is discussed including some current problems. The evidence for PVA as a satisfactory index of mV̇o2 under all physiological and pharmacological conditions is examined. Most pharmacological agents alter the intercept of the mV̇o2:PVA relationship but do not effect its slope: this result is interpreted to mean that the majority of current inotropic agents alter the energetic cost of calcium release/retrieval but not crossbridge efficiency.4. An attempt is made to establish the likely cost of a cardiac contraction in man. The use of newer technology (i) to estimate mV̇o2 via positron emission tomography and (ii) to measure the work and potential energy output of the heart per beat with conductance catheters, is explained.
ROLE OF ATRIAL NATRIURETIC PEPTIDE IN LONG‐TERM VOLUME HOMEOSTASIS
Authors: Lohmeier Thomas E. , Mizelle H. Leland , Reinhart Glenn A. 
Published: June 2007

SUMMARY1. Long‐term volume homeostasis is linked very closely to long‐term arterial pressure control through the renal‐body fluid feedback mechanism. A key feature of this control system is the ability of the kidneys to respond to changes in arterial pressure by altering renal excretion of salt and water, often referred to as renal‐pressure natriuresis.2. Quantitative studies indicate that ANP secretion is relatively sensitive to changes in atrial pressure and that the rate of hormonal secretion does not adapt to continuous long‐term stimulation.3. Under normal conditions, the renal‐body fluid feedback mechanism for arterial pressure control is very efficient in minimizing changes in body fluid volumes during alterations in sodium intake. Therefore, only small changes in atrial pressure and ANP secretion occur. Alterations in plasma ANP concentration within physiological levels have little effect on renal‐pressure natriuresis and, therefore, have little impact on volume homeostasis.4. When the renal‐body fluid feedback mechanism for arterial pressure control is impaired and body fluid volumes are elevated, such as in heart failure, large increases in atrial pressure and ANP secretion occur. The resultant pathophysiological plasma levels of ANP exert sustained natriuretic effects and chronically shift renal‐pressure natriuresis to lower arterial pressures. In the absence of this chronic effect of ANP on renal‐pressure natriuresis, reduced arterial pressure in compensated heart failure would result in protracted retention of salt and water and additional increments in body fluid volumes.
POTENTIATION OF NATRIURETIC PEPTIDES BY NEUTRAL ENDOPEPTIDASE INHIBITORS
Authors: Ann Seymour Andrea , Abboa‐Offei Benoni E. , Smith Patricia L. , Mathers Parker D. , Asaad Magdi M. , Rogers W. Lynn 
Published: June 2007

SUMMARY1. Inhibitors of neutral endopeptidase (NEP) EC 3.4.24.11 were developed to regulate endogenous levels of the natriuretic and vasodilatory hormone atrial natriuretic peptide (ANP). The selective NEP inhibitor SQ 28603 enhanced the increases in plasma ANP and urinary excretion of ANP, cyclic GMP and sodium stimulated by infusion of human ANP in conscious monkeys. SQ 28603 also potentiated the renal and depressor responses to rat brain natriuretic peptide (BNP) in conscious spontaneously hypertensive rats (SHR) and human BNP in conscious monkeys. Therefore, selective NEP inhibitors protected both natriuretic peptides from degradation in vivo and enhanced their biological activities.2. Selective NEP inhibitors lowered blood pressure in conscious DOCA/salt hypertensive rats and SHR with antihyper‐tensive activity similar to that of exogenous ANP. Furthermore, simultaneous treatment with an angiotensin converting enzyme (ACE) inhibitor enhanced the depressor activity of the NEP inhibitor in SHR.3. SQ 28603 stimulated urinary excretion of cyclic GMP and sodium in a dose‐related manner in conscious dogs with tachycardia‐induced heart failure. Addition of the ACE inhibitor captopril significantly reduced blood pressure and systemic vascular resistance while sustaining sodium excretion and increasing cardiac output, glomerular filtration rate and renal blood flow. Therefore, combined NEP and ACE inhibition produced a unique haemodynamic and renal profile in dogs with pacing‐induced heart failure.4. The novel dual metalloprotease inhibitor BMS‐182657 potentiated the renal responses to exogenous ANP and suppressed the pressor response to angiotensin I in conscious monkeys, indicating in vivo inhibition of both NEP and ACE. BMS‐182657 also reduced blood pressure and stimulated natriuresis in conscious 1‐kidney 1‐clip hypertensive dogs, demonstrating efficacy in a hypertensive model characterized by normal circulating levels of ANP and renin activity. Therefore, a dual metalloprotease inhibitor may offer a unique therapeutic approach for treatment of cardiovascular disorders.
RESPONSE TO ORTHOSTATIC STRESS PREDICTS OFFICE‐DAYTIME BLOOD PRESSURE DIFFERENCE, BUT NOT NOCTURNAL BLOOD PRESSURE FALL IN MILD ESSENTIAL HYPERTENSIVES: RESULTS OF THE HARVEST TRIAL
Authors: Narkiewicz Krzysztof , Piccolo Diana , Borella Paolo , Businaro Roberto , Zonzin Pietro , Palatini Paolo 
Published: June 2007

SUMMARY1. The aim of the present study was to evaluate whether postural blood pressure (BP) change could predict office‐daytime BP disparity and the nocturnal BP fall in young, mild essential hypertensives. We investigated 411 males aged between 18 and 45 years with never treated borderline to mild hypertension. BP was measured three times after a 5 min rest in the supine position and thereafter three times after 2 min of standing. The mean of six BP measurements obtained during two visits in the lying position was defined as office BP.2. Twenty‐four hour ambulatory BP monitoring was performed with either the A and D TM‐2420 model 7 or the ICR Spacelabs 90207. BP values were averaged for day—and nighttime periods. The nocturnal BP fall was defined as the difference between the average day—and night‐time BP.3. The standing‐lying difference was significantly inversely correlated with the office‐daytime difference for both systolic blood pressure (SBP) (r = ‐0.34, P 0.001) and diastolic blood pressure (DBP) (r = ‐0.24, P 0.001). These correlations did not change when the obese subjects (body mass index > 30 kg/m2) were excluded from the analysis. No significant correlation between standing‐lying difference and nocturnal BP fall was found.4. Our results indicate that white coat hypertension assessed as the office‐daytime BP disparity is partially related (in a negative fashion) to the BP reaction to standing. The postural BP change does not predict nocturnal BP fall in young, mild essential hypertensives.