bluuebunny/crossref_metadata_2025_split huggingface dataset:
CALCIUM‐CHANNEL BLOCKING AGENTS VERAPAMIL AND DILTIAZEM ARE INHIBITORS OF VASOPRESSIN‐INDUCED HUMAN PLATELET ACTIVATION
Authors: Anfossi Giovanni , Mularoni Elena , Massucco Paola , Cavalot Franco , Burzacca Serenella , Mattiello Luigi , Trovati Mariella 
Published: June 2007

SUMMARY1. This study investigated the influences of calcium‐channel blocking agents verapamil and diltiazem on platelet responses induced by arginine vasopressin (AVP) and lysine vasopressin (LVP).2. The substances inhibited platelet aggregation induced by both low and high AVP concentrations, LVP and adrenaline plus AVP. IC50 values of each drug are lower than those determined for ADP‐ and collagen‐elicited aggregation. Verapamil and diltiazem also decreased AVP‐induced thromboxane B2 synthesis.3. Other series of experiments showed that the addition of ethyleneglycol‐bis‐(β‐amino‐ethyl ether) N, N'‐tetra‐acetic acid to platelet‐rich plasma samples also prevented the platelet response to vasopressin polypeptides.4. Our data provide evidence that the effects of verapamil and diltiazem on vasopressin‐induced platelet responses may be directly related to inhibition of extracellular calcium entry.
DELAYED RECOVERY FROM NG‐NITRO‐L‐ARGININE IN THE CONSCIOUS SHEEP
Authors: Narkowic Christian K. , Vial Janet H. , Xu Xiao F. 
Published: June 2007

SUMMARY1. In the chronic, awake, instrumented sheep model NG‐nitro‐L‐arginine (NOLA) an inhibitor of nitric oxide synthesis, injected at a dose of 40 mg/kg, produced a significant increase in systolic blood pressure (from 110±6 to 145±8 mmHg after 5 min) which persisted for at least 1 h but returned to baseline after 24 h.2. When NOLA was repeated 1 and 4 days after the first injection, the blood pressure response was significantly attenuated, and at 1 day was no greater than the response to an equivalent volume of saline. The blood pressure response returned to the initial response with an 8 day interval between injections.3. There was no significant blood pressure response to 100 mL of saline before the NOLA injection; however, 1 and 4 days after NOLA there was a significant rise in blood pressure.
RECOMBINANT HUMAN INTERLEUKIN‐6 ENHANCES THE ANTIPROLIFERATION AND DIFFERENTIATION INDUCING EFFECTS OF RETINOIC ACID IN HL‐60 HUMAN MYELOID LEUKAEMIC CELLS
Authors: Hassan H. T. 
Published: June 2007

SUMMARY1. The effect of recombinant human interleukin‐6 on the antiproliferation and differentiation inducing actions of all‐trans retinoic acid in HL‐60 human myeloid leukaemia cells was studied in short‐term liquid suspension culture.2. Interleukin‐6 alone showed no significant effect on HL‐60 human myeloid leukaemia cells.3. The addition of interleukin‐6 to all‐trans retinoic acid‐treated cultures of HL‐60 human myeloid leukaemia cells significantly enhanced the desired antiproliferation effect of all‐trans retinoic acid.4. The combination of interleukin‐6 with all‐trans retinoic acid reduced the doses of all‐trans retinoic acid required to induce the same differentiation of HL‐60 cells as single agent by between 1.7‐ and 4.8‐fold; that is, the efficacy of all‐trans retinoic acid in inducing the differentiation of human myeloid leukaemia HL‐60 cells was increased up to 4.8 times by its combination with interleukin‐6.5. The combination of all‐trans retinoic acid and interleukin‐6 could provide an effective alternative therapy for elderly myeloid leukaemia patients.
ADRENALINE RELEASE BY THE HUMAN HEART
Authors: Esler Murray , Eisenhofer Graeme , Dart Anthony , Chin Jaye , Cox Helen , Lambert Gavin , Jennings Garry 
Published: June 2007

SUMMARY1. Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline to plasma in humans.2. No release of adrenaline could be detected from the heart, lungs, liver and kidneys at rest.3. With the relatively mild activation of the cardiac sympathetic outflow associated with mental challenge and isometric exercise, cardiac adrenaline release remained undetectable.4. During supine bicycle exercise, which increased cardiac noradrenaline release 10–20 fold, to a mean value of 128 ng/min, cardiac adrenaline release averaged 1.63 ng/min.5. Whether neuronal adrenaline release of this degree in the heart is sufficient to facilitate noradrenaline release and to augment sympathetically mediated cardiac responses remains to be tested.
THE MACROPHAGE AS AN INITIATOR OF ATHEROSCLEROSIS
Authors: Campbell Julie H. , Campbell Gordon R. 
Published: June 2007

SUMMARY1. Heparan sulfate proteoglycan in the basal lamina of smooth muscle cells is important in the maintenance of the ‘contractile’, high volume fraction of myofilaments (Vvmyo) phenotype. The mechanism by which this occurs may involve the continuous internalization of heparan sulfate by the smooth muscle cells themselves.2. One macrophage can degrade all the heparan sulfate from three smooth muscle cells by the action of heparan sulfate‐degrading enzymes in their lysosomes, thus leaving none available for internalization by the smooth muscle cell until it has synthesized more, and leading to the induction of smooth muscle phenotypic change from a high Vvmyo to a low Vvmyo.3. In this altered phenotype the smooth muscle cells proliferate in response to mitogens, synthesize large amounts of extracellular matrix and accumulate lipid, all characteristics of the smooth muscle cell in developing atheroma.
CHANGES IN CARDIAC ANGIOTENSIN CONVERTING ENZYME AFTER MYOCARDIAL INFARCTION AND HYPERTROPHY IN RATS
Authors: Johnston C. I. , Mooser V. , Sun Y. , Fabris B. 
Published: June 2007

SUMMARY1. Cardiac angiotensin‐converting enzyme (ACE) is localized in high concentration in cardiac valves, coronary vessels, right and left atrium and right and left ventricle.2. Cardiac ACE is functionally active in converting angiotension I to angiotensin II.3. The level of cardiac ACE measured by radioinhibitor binding or by quantitative in vitro autoradiography was greatly increased after experimental myocardial infarction in the rat. The increase was greatest in the fibrous scar tissue of the free left ventricular wall infarct, but there were also significant increases in the ACE concentration in the four chambers of the heart.4. Treatment with enalapril for 4 weeks following coronary ligation inhibited cardiac ACE, including the high levels found in the scar in the left ventricular free wall.5. There was a close relationship between the systolic blood pressure and left ventricular mass in several models of experimental hypertension, despite varying degrees of activation of the renin–angiotensin system. However no relationship between the degree of left ventricular hypertrophy and changes in cardiac ACE could be determined.6. Inhibition of cardiac ACE may contribute to the beneficial effect of ACE inhibitors in cardiac hypertrophy and remodelling, and may play a part in the cardioprotective role of ACE inhibitor.
IONIC MECHANISMS REGULATING SODIUM ENTRY INTO VASCULAR SMOOTH MUSCLE
Authors: Bobik Alex , Little Peter J. , Neylon Craig B. 
Published: June 2007

SUMMARY1. Na+/H+ exchange, an ethylisopropylamiloride (EIPA)‐sensitive Na+ and HCO3‐ dependent system and a diisothio‐cyanatostilbenedisulphonic acid (DIDS)‐sensitive Na+ and HCO3‐ transporter, contribute to sodium influx and intracellular pH (pHi) regulation in vascular smooth muscle.2. In cultured cells from the human internal mammary artery, Na+/H+ exchange and the EIPA‐sensitive Na+ and HCO3‐ dependent system contribute about 80% to basal sodium influx. The residual Na+ influx is both EIPA and DIDS‐insensitive.3. Sodium influx via these mechanisms influences the ability of vascular smooth muscle to synthesize protein late in the G1 phase of the mitotic cell cycle. This, in turn, affects DNA biosysthesis.4. These Na+ exchanges/transporters have the capability to facilitate the development of vascular hypertrophy in hypertension.
EFFECT OF PARATHYROIDECTOMY ON DEVELOPMENT OF HYPERTENSION AND ATRIAL RESPONSIVENESS IN SPONTANEOUS HYPERTENSIVE RATS
Authors: Schleiffer R. , Ghysel‐Burton J. , Finet M. , Gairard A. 
Published: June 2007

SUMMARY1. In order to further clarify the relationships between parathyroid function and development of hypertension, the effects of parathyroidectomy (PTX) on blood pressure and on responsiveness of atria isolated from spontaneous hypertensive rats (SHR) were examined.2. PTX was carried out in 6‐week‐old SHR and normotensive Wistar rats. The experiments were performed 2 weeks after surgery.3. PTX reduced the plasma calcium concentration and decreased atrial calcium content in SHR. On the other hand, basal contractile force and beat frequency of isolated atria were higher in PTX SHR than in sham‐operated SHR. In response to cumulative addition of isoprenaline, atria from PTX SHR displayed diminished inotropic and chronotropic responses compared with sham‐operated SHR. Similar results were obtained in atria isolated from Wistar rats. When calcium sensitivity was studied in atria from Wistar rats, basal and isoprenaline‐induced maximum contractile forces were higher in PTX group than in the sham‐operated group. Nevertheless, basal and isoprenaline‐induced maximum contractile forces, determined at the respective plasma ionized calcium concentration of PTX and sham‐operated groups (0.83 and 1.22 mmol/L), were not significantly different.4. Our results do not favour a role for alteration in atrial activity as a causal mechanism in delayed development of experimental genetic hypertension after parathyroidectomy.
INHIBITION OF CYCLIC GMP PHOSPHODIESTERASE BY XANTHINE DERIVATIVES RELAXES GUINEA‐PIG TRACHEALIS SMOOTH MUSCLE
Authors: Tanaka Hitoshi , Ogawa Kenji , Takagi Kenzo , Satake Tatsuo , Hidaka Hiroyoshi 
Published: June 2007

SUMMARY1. For the purpose of clarifying the mechanism of the airways smooth muscle relaxant action of xanthines, cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE) from guinea‐pig trachealis muscle was purified with diethylaminoethyl ether (DEAE) cellulose column chromatography.2. Five 3‐alkylxanthines (3‐methylxanthine, 3‐ethylxanthine, 3‐n‐propylxanthine (enprofylline), 3‐n‐butylxanthine, and 3‐iso‐butylxanthine), and five 1‐methyl‐3‐alkylxanthines (1‐methyl‐3‐methyl‐xanthine (theophylline), 1‐methyl‐3‐ethylxanthine, 1‐methyl‐3‐n‐propylxanthine, 1‐methyl‐3‐n‐butyl‐xanthine, and 1‐methyl‐3‐iso‐butylxanthine (IBMX)) were compared in terms of purified cyclic GMP PDE inhibition. The relationship between the structure and inhibition of cyclic GMP PDE was studied.3. The –log EC50 values for relaxation of spontaneous tone of isolated guinea‐pig trachealis preparations by the 3‐alkylxanthines and 1‐methyl‐3‐alkylxanthines were determined.4. The five 1‐methyl‐3‐alkylxanthines were each more potent in relaxing isolated trachealis smooth muscle than the corresponding 3‐alkylxanthines. The 1‐methyl‐3‐alkylxanthines were also more potent than the corresponding 3‐alkylxanthines in their cyclic GMP PDE inhibitory effect. There was a strong positive correlation between the concentration of inhibitor which inhibited hydrolysis by 50% (IC50) values for cyclic GMP PDE inhibition by the xanthine derivatives and their EC50 values for trachealis muscle relaxation.5. It is suggested that the mechanism by which xanthine derivatives relax trachealis smooth muscle involves inhibition of cyclic GMP PDE in addition to inhibition of cyclic adenosine monophosphate PDE.
FAILURE OF THE KETY‐SCHMIDT NITROUS OXIDE METHOD FOR DETERMINATION OF MYOCARDIAL BLOOD FLOW
Authors: Reid Michael A. , Mather Laurence E. , Runciman William B. , McLean Colin F. 
Published: June 2007

SUMMARY1. The reliability of the Kety‐Schmidt nitrous oxide (N2O) blood–tissue equilibration method was examined in 50 studies of myocardial blood flow in seven conscious, unrestrained sheep using a newly developed carefully validated gas chromatographic assay for N2O.2. In 10 studies the arterial and coronary sinus N2O blood concentration–time curves converged as expected at the end of the 10 min sampling period. In 14 studies they crossed over, and in 26 studies, the curves failed to converge.3. A survey of the literature revealed that such results have been encountered previously but have not been accorded particular significance. An ultimate matching equilibrium between arterial and venous blood N2O concentration–time curves is, however, fundamental to the validity of the method.4. The results indicate that the use of the Kety‐Schmidt method with N2O as the indicator gas is invalid as applied to the measurement of myocardial blood flow in this preparation.
SODIUM AND VOLUME DYSREGULATION AFTER APPARENTLY NORMAL PREGNANCY IS SUGGESTED BY ABNORMAL LEVELS OF ATRIAL NATRIURETIC PEPTIDE, RENIN AND ALDOSTERONE
Authors: Finn Wendy L. , Tunny Terry J. , Klemm Shelley A. , Jones Ian S. , De Voss Kerry , Gordon Richard D. 
Published: June 2007

SUMMARY1. Plasma atrial natriuretic peptide (ANP), renin activity, aldosterone, sodium, potassium and serum total protein and albumin during and after 14 normal pregnancies were compared with age‐matched controls.2. None developed toxaemia and all delivered healthy babies.3. During pregnancy, plasma renin activity and aldosterone were significantly (P<0.01) higher and potassium, total protein and albumin significantly lower (P<0.01) than in controls, while ANP was not different from the control level.4. At 6–13 weeks postpartum, a significant (P<0.01) suppression of renin and aldosterone was accompanied by significant (P<0.01) elevation of atrial natriuretic peptide when compared with controls.5. The hormonal changes are consistent with ‘effective plasma volume’ reduction during pregnancy and persistent volume expansion after pregnancy, perhaps due to a renal glomerular lesion sustained late in pregnancy. In contrast, levels of potassium, total protein and albumin are consistent with haemodilution during pregnancy and its correction postpartum.6. Measurements available in seven women 40–120 weeks postpartum showed normal renin and aldosterone levels in most, but ANP was still elevated.7. Pregnancy may have a protracted effect on volume regulation.
URINARY STEROID PROFILES AND ALOCHOL‐RELATED BLOOD PRESSURE ELEVATION
Authors: Mori T. A. , Puddey I. B. , Wilkinson S. P. , Beilin L. J. , Vandongen R. 
Published: June 2007

SUMMARY1. From an earlier cross‐sectional survey of 343 public servants, 15 pairs of non‐smoking teetotallers and heavy drinkers (alcohol intake more than 350 mL/week) were matched for age and adiposity and utilized for a case‐control study of the effects of alcohol on 11β‐hydroxysteroid dehydrogenase (11β‐OHSD) activity and blood pressure.2. Two successive 24 h urine collections were analysed by radio‐immunoassay (RIA) for cortisol excretion, and for the cortisol and cortisone metabolites, tetrahydrocortisol (THC), allo‐tetrahydrocortisol (allo‐THC) and tetrahydrocortisone (THE), by capillary column gas chromatography.3. Heavy drinkers had higher systolic and diastolic blood pressure (BP) than teetotallers (132.6 ± 2.5 vs 123.2 ± 1.3 and 78.7 ± 1.6 vs 71.7 ± 1.4, respectively; unpaired t‐test, P<0.01). Twenty‐four‐hour urinary sodium and cortisol excretion were similar in the two groups.4. The THC plus allo‐THC: THE ratio was similar in drinkers and teetotallers (1.81 ± 0.20 vs 2.03 ± 0.20), consistent with no effect of alcohol on 11β‐OHSD activity. The ratio of THC to allo‐THC was increased in drinkers compared with teetotallers (1.49 ± 0.18 vs 1.05 ± 0.13; unpaired t‐test, P<0.05), consistent with either a decrease in 5α‐reductase activity or an increase in 5β‐reductase activity.5. This study provides no evidence for alcohol‐related inhibition of 11β‐OHSD, despite substantially higher blood pressures in heavy drinkers compared to teetotallers. Such an effect is, therefore, unlikely to contribute significantly to the mechanism of alcohol‐related hypertension. The increase in the THC: allo‐THC ratio is consistent with a redox effect on steroid metabolism.
AUTORADIOGRAPHIC LOCALIZATION OF ANGIOTENSIN‐CONVERTING ENZYME AND ANGIOTENSIN II BINDING SITES IN EARLY ATHEROMA‐LIKE LESIONS IN RABBIT ARTERIES
Authors: Zambetis‐Bellesis Maria , Dusting Gregory J. , Mendelsohn Frederick A. O. , Richardson Karen 
Published: June 2007

SUMMARY1. Early atheroma‐like lesions in rabbits are associated with increased sensitivity to serotonin. The localization and distribution of angiotensin‐converting enzyme (ACE) and angiotensin II (AII) binding sites has been studied in these developing lesions by quantitative in vitro autoradiography.2. In sham‐operated control vessels, ACE was localized predominantly to intimal and adventitial sites, whereas in lesioned arteries the level of ACE detected in these regions was significantly reduced.3. In control vessels AII receptor binding was distributed largely in the outer media, whereas in lesioned vessels AII receptor binding was dispersed throughout the media with the highest levels of binding in the outer media.4. There was a significant amount of binding associated with ACE and with AII receptors in the extra‐adventitial inflammatory tissue of lesioned arteries.5. Apparent loss of ACE from intimal and adventitial sites may be a consequence of tissue remodelling and cellular proliferation, while the appearance of ACE in abnormal sites could play a role in AII production by the vessel wall. The role of ACE and AII in the developing atheroma‐like lesions needs to be investigated further.
EFFECT OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITION ON RENAL NOREPINEPHRINE SPILLOVER RATE AND BAROREFLEX RESPONSES IN CONSCIOUS RABBITS
Authors: Noshiro Takao , Way Diana , McGrath Barry P. 
Published: June 2007

SUMMARY1. To evaluate the effects of angiotensin‐converting enzyme (ACE) inhibition on sympathetic nerve activity, renal and total norepinephrine (NE) spillover rates were examined under control conditions and during enalaprilat infusion at rest and in response to sodium nitroprusside (SNP)‐induced hypotension.2. Resting renal and total NE spillover rate during enalaprilat infusion were similar to control values.3. During SNP infusion at 10 μg/kg per min, renal NE spillover rate increased by 26% in enalaprilat‐treated group and by 39% in controls, in response to falls in mean arterial pressure (MAP) of 25 and 19% respectively.4. During sympathetic stimulation induced by SNP, total NE spillover rate was significantly increased in both groups, but the 50% (s.e.m. = 12) increase in the enalaprilat‐treated group was less (P<0.05) than the 97% (s.e.m. = 16) change observed in controls.5. Enalaprilat treatment resulted in a higher renal to total NE spillover ratio (P<0.05). The ratio fell in parallel in both groups during SNP‐induced hypotension.6. This study indicates that the sympathetic nervous system interacts dynamically with the renin‐angiotensin system during hypotensive stimulation but this occurs predominantly at sites other than the kidney.
L‐NITROARGININE INCREASES BLOOD PRESSURE IN THE RAT
Authors: Kobayashi Yuta , Ikeda Katsumi , Shinozuka Kazumasa , Nara Yasuo , Yamori Yukio , Hattori Keisuke 
Published: June 2007

SUMMARY1. Effects of administration of NG‐nitro‐L‐arginine (NO2Arg), a guanidino nitroarginine derivative, for 1 week on blood pressure and some vascular responses of rats were studied.2. A significant rise of the systolic blood pressure was observed after the administration of NO2Arg with food (0.023% in weight, about 2.8 mg of NO2Arg per rat per day). Relaxation by acetylcholine decreased markedly in ring preparations of the thoracic aorta of NO2Arg‐treated rats. However, glyceryltrinitrate‐induced relaxation was not reduced after NO2Arg administration, suggesting that NO2Arg administration specifically inhibited endothelium‐dependent relaxation.3. An increase of blood pressure may be because oral administration of NO2Arg inhibited endothelium‐dependent relaxation in vivo suggesting that the release of EDRF is important in physiological control of blood pressure.
EFFECT OF GONADOTROPINS AND PREGNANCY ON PRORENIN AND RENIN IN THE RAT
Authors: Nielsen Arne Høj , Hagemann Arne , Poulsen Knud 
Published: June 2007

SUMMARY1. Stimulation of adult female rats with pregnant mare serum gonadotropin (PMSG) and human chorion gonadotropin (hCG) increased active plasma renin about two‐fold, but caused only a slight increase of plasma prorenin. The concentrations of active renin and prorenin in the ovaries, and active renin in the uterus all increased about two‐fold 2 days after stimulation with PMSG. The prorenin in the uterus was below detection in unstimulated rats and did not change consistently after PMSG.2. Active renin and prorenin in plasma were unchanged in relation to pregnancy, except for a slight decrease of prorenin in the third trimester. In the first and third trimester the concentration in the ovaries of active renin and prorenin was decreased to about one‐third of that in normal female rats. In contrast active renin in the uterus was increased about two‐fold in the first trimester, whereas prorenin did not change consistently.3. Our results confirm that gonadotropins and pregnancy affect the renin–angiotensin system in rats. However, the changes in the plasma seem to be much smaller than those previously reported in humans. Accordingly, our results do not support a systemic role of prorenin for reproduction in the rat.
DILTIAZEM AND VERAPAMIL LOWER BLOOD PRESSURE IN THE UNANAESTHETIZED RAT THROUGH CNS MECHANISMS INVOLVING ENDOGENOUS OPIOIDS
Authors: Rabkin Simon W. 
Published: June 2007

SUMMARY1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intra‐cerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 μg/kg, or their diluent.2. Diltiazem, at both 10 and 50 μg/kg i.c.v., produced significant (P<0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 μg/kg but not at 10 μg/kg i.c.v., produced a significant (P<0.05) decrease in blood pressure, while both doses significantly (P<0.05) decreased heart rate.3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 μg/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone.4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pressure.