bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALTERED LEVELS OF NEUROPEPTIDES IN THE MEDULLA AND SPINAL CORD OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Jarrott B. , Lewis S. J. , Maccarrone C. , Shulkes A. 
Published: June 2007

SUMMARY1. Spontaneously hypertensive rats (SHR) are useful for investigating the possible pathophysiological and neurochemical basis of human essential hypertension.2. The accepted pathogenic mechanism of hypertension in SHR is an increased central sympathetic drive which results in an increased peripheral resistance.3. The neurochemical basis of the increased sympathetic drive is unknown. The observation that there are reduced levels of neuropeptides (vasoactive intestinal peptide, neuropeptide Y, cholecystokinin octapeptide, neurotensin and calcitonin gene related peptide) in the spinal cord in SHR rats compared with age and gender matched Wistar‐Kyoto normotensive rats could provide a basis for understanding the mechanism of hypertension in SHR.
RECEPTORS AND STEROID‐DEPENDENT HYPERTENSION
Authors: Coghlan John P. , Reid Amanda F. , Spence Campbell D. , Scoggins Bruce A. , Whitworth Judith A. 
Published: June 2007

SUMMARY1. Repeated observations indicate that ACTH administration causes hypertension.2. Development of hypertension requires 17α‐hydroxyprogesterone and 17α, 20α‐dihydroxy‐4‐pregnene‐3‐one to be present in association with other steroids.3. The hypertensinogenic activity of corticosteroids is distinct from their glucocorticoid and mineralocorticoid effects.4. The location of central and peripheral receptors for this hypertensinogenic activity is not clear.5. The physiological mechanisms that mediate the response are unknown, though a number of potential mediating effects has been demonstrated.6. The overall importance of unusual steroids and steroid actions in human essential hypertension still requires elucidation.
VOLUNTARY BLOOD PRESSURE CONTROL USING CONTINUOUS SYSTOLIC BLOOD PRESSURE BIOFEEDBACK
Authors: Cejnar M. , Hunyor S. N. , Liggins G. W. , Bartrop R. 
Published: June 2007

SUMMARY1. Ability to alter blood pressure (BP) acutely with continuous systolic (SBP) BP biofeedback was assessed in volunteers using a new non‐invasive finger BP monitor.2. Reliability of finger BP measurement was demonstrated in six hypertensive subjects (21–60 years), by beat‐to‐beat comparison with brachial intra‐arterial BP over 90 min. Wide variation of BP was achieved by physiological manoeuvres. Mean error of finger BP was ‐3.0/‐2.2 mmHg with intra‐subject s.d. of 7.2/5.4 mmHg.3. Thirteen normotensives (21–51 years) were paid to undergo 30 trials of SBP biofeedback in six sessions over 3 weeks. The SBP trend was displayed on a monitor with appropriately ‘shaped’ targets; each trial consisted of BP‐raising and ‐lowering periods of 45 and 90 s respectively with intervening 45 s baselines.4. Nine subjects raised BP, on analysis of the last 10 trials, by an average of 18.8 mmHg while five of the 13 successfully lowered BP by an average of 10.0 mmHg. BP lowering was best achieved by diminishing respiratory rate and depth, and muscular relaxation.5. Demonstration of large BP reductions in five of 13 normotensives using strategies applicable to longer training sessions warrants further investigations in hypertensive subjects, focusing on mediating mechanisms and transfer of effect beyond the laboratory.
INHIBITION OF SEROTONIN‐INDUCED ACTH RELEASE IN MAN BY CLONIDINE
Authors: Jackson R. V. , Grice J. E. , Jackson A. J. , Vella R. D. , Armour M. B. 
Published: June 2007

SUMMARY1. Clonidine, an α2‐adrenergic agonist, is thought to inhibit noradrenergic neuronal activity (NNA) in the central nervous system (CNS) by a presynaptic α2‐receptor mechanism. Central NNA is thought to be the primary monoaminergic stimulus to pituitary ACTH release. Fenfluramine, a serotonin releasing agent and uptake inhibitor, causes ACTH release in normal man.2. The present study investigated the effect of clonidine on fenfluramine‐induced ACTH release in six normal volunteers. Four protocols were used: 1.5 mg/kg body weight oral fenfluramine; 4.3 μg/kg body weight oral clonidine; oral clonidine + oral fenfluramine 1 h later; placebo clonidine. Plasma ACTH and cortisol were measured at intervals for 5 h after clonidine and for 4 h after fenfluramine.3. The mean plasma ACTH and cortisol levels and the mean maximal changes in these levels were significantly lower during the clonidine + fenfluramine test than during fenfluramine alone. Plasma ACTH and cortisol levels were not lowered significantly more by clonidine than by placebo.4. In conclusion, clonidine blocked the ACTH‐releasing activity of fenfluramine in normal humans. This inhibition of active ACTH release may result from clonidine blockade of fenfluramine‐induced activation of central NNA. Clonidine alone was no more effective than placebo in lowering plasma ACTH and cortisol.
ATTENUATED RENAL RESPONSE TO ATRIAL NATRIURETIC PEPTIDE INFUSION IN RATS WITH HEART FAILURE
Authors: Kohzuki Masahiro , Hodsman G. Peter , Harrison Richard W. , Johnston Colin I. 
Published: June 2007

SUMMARY1. The natriuretic and diuretic effects of three atrial natriuretic peptide (ANP) infusion rates were examined in rats 4 weeks after myocardial infarction induced by left coronary artery ligation.2. The natriuretic and diuretic effects of ANP were observed in controls and rats with infarction, but the effects were significantly attenuated in the latter.3. Rats with chronic left heart failure were less sensitive to the renal effects of ANP compared with controls.4. Impaired sodium and water excretion in chronic heart failure may be due partly to an attenuated renal response to ANP.
SERUM LIPIDS IN INSULIN‐DEPENDENT DIABETICS ARE MARKEDLY ALTERED BY DIETARY FISH OILS
Authors: Mori Trevor A. , Vandongen Robert , Masarei John R. L. , Dunbar Diana , Stanton Kim G. 
Published: June 2007

SUMMARY1. The effect of dietary fish oil supplementation on serum lipids was examined in normolipidaemic insulin‐dependent male diabetics and healthy controls. Fish oil was given as Max eicosapentaenoic acid (EPA), 15 g daily (equivalent to 2.7 g/day of EPA) for 3 weeks.2. There was a substantial increase in EPA but a depletion of arachidonic acid content of platelet phospholipids.3. Diabetics showed a rise in total cholesterol, attributable to increases in low density and high density lipoprotein (LDL and HDL) cholesterol. The rise in HDL cholesterol was largely due to an increase in its HDL2 subclass. Similar changes were found in the healthy men although these were not as marked. A decrease in triglycerides was observed in both diabetics and normal controls.4. Generally, diabetics showed greater changes in lipid concentrations which may suggest an altered metabolic response to w3 fatty acids. Therefore, the possible detrimental effect of the rise in total cholesterol and LDL cholesterol following fish oil administration may be offset by the increase in the protective HDL2 subclass.
VASCULAR SMOOTH MUSCLE POLYPLOIDY IN THE DEVELOPMENT AND REGRESSION OF HYPERTENSION
Authors: Black M. J. , Adams M. A. , Bobik A. , Campbell J. H. , Campbell G. R. 
Published: June 2007

SUMMARY1. Two groups of spontaneously hypertensive rats (SHR) were treated with enalapril (25–30 mg/kg per day): Group I received treatment from 4 to 14 weeks of age to inhibit development of hypertension and Group R received the drug from 14 to 20 weeks of age to reverse established hypertension.2. Systolic blood pressure, ploidy of aortic smooth muscle cells (flow cytometric DNA analysis) and aortic hypertrophy (medial cross‐sectional area) were determined at times both during and after enalapril treatment (up to 30 weeks).3. Enalapril treatment normalized blood pressure to that of age‐matched Wistar‐Kyoto rats in both groups. Blood pressure rose again following cessation of treatment.4. In untreated SHR the incidence of polyploid cells increased concomitantly with increasing pressure throughout the time studied, whereas in Group I the incidence remained low. In Group R, the incidence of polyploidy directly paralleled both the decrease (normalization) and the rise in blood pressure following cessation of treatment.5. Hence, the incidence of vascular smooth muscle cell polyploidy is not simply a result of growth of the vessel with increasing age of the SHR, but parallels inhibition, reversal, and redevelopment of hypertension.
RENIN RESPONSE TO GRADED HAEMORRHAGE IN CONSCIOUS RATS
Authors: Roarty Timothy P. , Raff Hershel 
Published: June 2007

SUMMARY1. A haemorrhage volume/plasma renin activity (PRA) response relationship was established for five levels of acute haemorrhage ranging from 1.5 to 15 ml/kg in conscious rats. In addition, the effects of chronic indomethacin and/or acute propranolol administration on the PRA response to 5 and 10 ml/kg haemorrhage was assessed.2. Mean arterial pressure decreased in a haemorrhage volume dependent manner which was not significantly altered by indomethacin and/or propranolol.3. Haemorrhage volumes of 1.5 and 3.0 ml/kg did not significantly alter PRA. At haemorrhage volumes of 5.0 ml/kg and higher, PRA increased in a volume‐dependent manner. Propranolol decreased basal PRA levels but had little effect on the response to haemorrhage. Indomethacin had no effect on basal PRA, but attenuated the response to haemorrhage somewhat. When propranolol and indomethacin were combined, the PRA response to haemorrhage was significantly attenuated.4. The conscious cannulated rat model exhibits predictable and reproducible renin responses to haemorrhage and is an excellent model for studying the control of renin secretion.
INHIBITION OF VASODILATATION BY METHYLENE BLUE IN LARGE AND SMALL ARTERIES OF THE DOG HINDLIMB IN VIVO
Authors: Sobey C. G. , Woodman O. L. , Dusting G. J. 
Published: June 2007

b1. Injection of acetylcholine (ACh, 0.0005–2 μg/kg) or glyceryl trinitrate (GTN, 0.01–20 μg/kg) into the femoral artery increased femoral artery diameter, femoral blood flow and heart rate, and reduced femoral vascular resistance and systemic arterial blood pressure in anaesthetized dogs. The intravenous (i.v.) injection of ACh (2 μg/kg) produced a small decrease in systemic arterial pressure and an increase in heart rate, but did not dilate the hindlimb vessels.2. Methylene blue, a guanylate cyclase inhibitor, continuously infused into the femoral artery (10 mg/min), attenuated the increase in femoral artery diameter and femoral blood flow, and the decrease in femoral vascular resistance produced by intra‐arterial injections of both ACh and GTN.3. In addition, methylene blue potentiated the decrease in systemic arterial pressure produced by ACh (injected directly into the femoral artery or i.v.), but did not affect the depressor response to GTN. This selective potentiation of ACh‐induced hypotension was not affected by autonomic ganglion blockade with hexamethonium (25 mg/kg, i.v.).4. These results suggest that both ACh‐and GTN‐induced vasodilatation in vivo occurs through a mechanism involving guanylate cyclase activation in large arteries and resistance vessels in the dog hindlimb. Methylene blue inhibited the local vasodilator actions of ACh in the femoral vasculature despite potentiating the systemic depressor response to that agent.
ACTION OF MEFLOQUINE ON AGONIST‐INDUCED CONTRACTIONS OF THE GUINEA‐PIG ISOLATED ILEUM
Authors: Go M. L. , Lee H. S. 
Published: June 2007

b1. Responses of the guinea‐pig isolated ileum to cumulative concentrations of acetylcholine (ACh), histamine (H), and prostaglandin E2 (PGE2) were obtained in the presence or absence of mefloquine or quinine.2. The effects of increasing the external calcium concentration and the presence of a low concentration (1.8 nmol/l) of PGE2 on the mefloquine‐and quinine‐induced inhibition of the ACh cumulative dose‐response curves were also investigated.3. Mefloquine (1–10 μmol/l) and quinine (50–100 μmol/l) both caused a dose‐dependent non‐parallel right shift of the log concentration‐response curve of every agonist. Mefloquine is a more potent inhibitor of PGE2‐induced responses whereas quinine inhibited all three agonist‐induced responses to the same extent.4. Increasing the external calcium concentration enhanced the inhibitory effects of both drugs on ACh‐induced responses. Pre‐incubation with 1.8 nmol/l PGE2 had a similar effect.5. The actions of mefloquine on ACh‐and H‐induced contractions are non‐specific, like other antimalarials, but its greater inhibitory action on PGE2 may involve a more complex effect.
ENDOTHELIUM‐DEPENDENT INHIBITION OF SYMPATHETIC VASOCONSTRICTION BY FRUSEMIDE ADMINISTRATION TO RATS
Authors: Gerkens J. F. , Armsworth S. J. , Dosen P. J. , Smith A. J. 
Published: June 2007

SUMMARY1. Segments of the tail artery of the rat were cannulated at both ends and mounted in an organ bath filled with Krebs solution.2. Using an extracorporeal circuit, blood was pumped at a constant 2 ml/min from the carotid artery of anaesthetized rats to perfuse the segment of tail artery, and returned to the donor rat via the jugular vein.3. Peri‐arterial electrical stimulation of the ex vivo blood perfused tail artery at 5 Hz produced vasoconstriction and an increase in perfusion pressure.4. The intravenous administration of frusemide 5 mg/kg to the donor rat resulted in an inhibition of the vasoconstrictor responses of the perfused tail artery segment. Diuresis‐induced losses of volume and frusemide were prevented by a urinary bladder‐venous shunt.5. Removal of the endothelium from the tail artery segment, by perfusion with dry gas for 4 min, prevented the vasoconstrictor‐inhibitory effect of frusemide administration. Removal of the endothelium was confirmed histologically and by the absence of a vasodilator response to acetylcholine.6. On the basis of these and previous results it is concluded that parenteral frusemide administration releases an unidentified but non‐prostanoid hormone from the kidney which produces an endothelium‐dependent inhibition of sympathetic vascoconstriction.
EFFECT OF DIABETES MELLITUS ON SALIVARY PARACETAMOL ELIMINATION
Authors: Adithan C. , Danda D. , Swaminathan R. P. , Indhiresan J. , Shashindran C. H. , Bapna J. S. , Chandrasekar S. 
Published: June 2007

SUMMARY1. Salivary elimination of paracetamol was studied in nine type I and ten type II diabetics. Ten healthy volunteers served as a control group.2. A significant increase in the elimination half‐life (t1/2) and apparent volume of distribution was observed in type I diabetics compared with controls. Clearance rate (CL) was not significantly altered.3. In type II diabetics paracetamol elimination t1/2 was significantly increased with a corresponding decrease in CL. Apparent volume of distribution of the drug was not significantly different.4. Paracetamol elimination t1/2 had significant correlation with fasting blood sugar values.
BOOK REVIEWS
Authors: CHRISTOPHIDIS NICHOLAS 
Published: June 2007

Self‐Assessment in Clinical Pharmacology. By Henry L. Elliott, MD, MRCP, John L. Reid, MD, FRCP, Peter C. Rubin, MD, MRCP and Brian Whiting, MD, FRCP. Pages viii + 154, 14 cm ± 21 cm. Blackwell Scientific Publications: Oxford, 1987. Price $24.00. IVAN. Living with Parkinson's Disease. By Ivan Vaughan. Pages 224. Macmillan, London, 1988. $12.95.
CONTROL OF GLOMERULOSA CELL FUNCTION BY ANGIOTENSIN II: TRANSDUCTION BY G‐PROTEINS AND INOSITOL POLYPHOSPHATES*
Authors: Catt Kevin J. , Balla Tamas , Baukal Albert J. , Hausdorff William P. , Aguilera Greti 
Published: June 2007

SUMMARY1. The receptor‐activated mechanisms that mediate the steroidogenic actions of angiotensin II (AII) have been characterized in rat and bovine adrenal glomerulosa cells. In rat adrenal cells, the AII receptor is coupled to a guanine nucleotide inhibitory protein which reduces adenylate cyclase activity and cyclic AMP production. However, receptor‐mediated stimulation of aldosterone production by AII is exerted through a separate pertussis‐insensitive nucleotide regulatory protein that subserves coupling of activated receptors to phospholipase C.2. In AII‐stimulated glomerulosa cells, hydrolysis of phosphatidylinositol (4,5)‐bisphosphate (PIP2) by phospholipase C yields diacylglycerol and inositol 1,4,5‐trisphosphate (Ins‐P3), which act as second messengers by activating calcium‐calmodulin and calcium‐phospholipid dependent protein kinase pathways. Ins‐1,4,5‐P3 is a potent stimulus of intracellular calcium mobilization, and is promptly inactivated by two major routes of metabolism. Direct degradation of Ins‐1,4,5‐P3 by a 5‐phosphatase gives inositol 1,4‐bisphosphate which in turn is metabolized to inositol‐4‐monophosphate. The latter product can be derived only from higher inositol phosphates, and thus serves as a specific marker of polyphosphoinositide breakdown in agonist‐stimulated cells. In contrast, inositol‐1‐phosphate is largely derived from phosphatidylinositol hydrolysis, which is not increased during the initial phase of AII action.3. Ins‐1,4,5‐P3 formed in AII‐stimulated glomerulosa cells is also phosphorylated by a calcium‐calmodulin dependent 3‐kinase to form inositol 1,3,4,5‐tetrakisphosphate (Ins‐P4), which is rapidly dephosphorylated to the biologically inactive Ins‐1,4,5‐P3 isomer, Ins‐1,3,4‐trisphosphate. The latter metabolite, like Ins‐1,4,5‐P3, is both degraded to lower phosphates (Ins‐3,4, P2 and Ins‐1,3‐P2) and phosphorylated to form a new tetrakisphosphate isomer (Ins‐1,3,4,6‐P4). Ins‐1,4,5‐P3 formed during AII action is bound with high affinity to specific intracellular receptors through which InsP3 causes calcium mobilization during the initiation of cellular responses to AII and other calcium‐dependent ligands.
EFFECT OF DIETARY FISH OILS ON THE FORMATION OF LEUKOTRIENE B4 AND B5, THROMBOXANE AND PLATELET ACTIVATING FACTOR BY RAT LEUKOCYTES
Authors: Croft Kevin D. , Codde James P. , Barden Anne , Vandongen Robert , Beilin Lawrence J. 
Published: June 2007

SUMMARY1. This study investigates the effect of dietary eicosapentaenoic acid (EPA), in the form of ‘Max EPA’ fish oil, on leukotriene B4 (LTB4) production in ionophore‐stimulated rat leukocytes. Male Wistar rats (200–250 g) were fed for 3 weeks on a synthetic chow supplemented with either 10% by weight Max EPA oil or a coconut oil/safflower oil mixture.2. The EPA‐rich diet significantly increased the EPA content of leukocyte phospholipids and decreased the arachidonic acid level by 35% (P < 0.001) compared with the control diet.3. The concentration of leukotrienes in the ionophore (A23187) stimulated leukocytes was measured by reverse‐phase HPLC using prostaglandin B2 as the internal standard. The EPA‐supplemented diet caused a 50% decrease in LTB4 production (P < 0.001) and a concomitant increase in the formation of the biologically less active LTB5 compared with the control diet. The amount of LTB4 and LTB5 produced by stimulated leukocytes closely resembled the changes in arachidonic acid and EPA content of leukocyte phospholipids.4. Thromboxane B2 (TxB2) production in stimulated leukocytes from the EPA‐fed animals was also decreased compared with the control group.5. Although the formation of platelet activating factor by stimulated leukocytes was not altered by dietary treatment, the ability of an EPA‐rich diet to decrease LTB4 and TxB2 production suggests that these diets may attenuate leukocyte activity and have useful anti‐inflammatory effects.
INHIBITION BY COCAINE OF NORADRENALINE RELEASE FROM SYMPATHETIC NERVES IN THE RABBIT EAR ARTERY
Authors: Parker D. A. S. , de la Lande I. S. 
Published: June 2007

SUMMARY1. Effects of cocaine on release of noradrenaline (NA) from sympathetic nerves were studied in the isolated perfused central artery of the rabbit ear. Indices of release were the vasoconstrictor response to nerve stimulation and stimulation‐induced overflow of radioactivity after the nerves had been loaded with [3H]‐NA. The overflow studies were carried out on phenoxybenzamine‐treated arteries to eliminate the effect of cocaine on neuronal uptake.2. Cocaine enhanced the constrictor responses of the artery to stimulation in concentrations of 3 and 30 μmol/l, but in higher concentrations (tested up to 300 μmol/l) the enhancement declined and was replaced by inhibition. Responses to extraluminal NA remained enhanced throughout the concentration range (tested up to 150 μmol/l).3. In contrast, cocaine depressed the overflow of radioactivity, the effect being detectable in a concentration of 3 μmol/l (a decrease of 15%); the decrease was 40% at the highest concentration tested (90 μmol/l).4. It is suggested that when assessed in terms of the vasoconstrictor response, inhibition of transmitter release by cocaine is masked by inhibition of neuronal uptake except in high concentrations of cocaine.
EFFECT OF SHORT COURSE CHEMOTHERAPY ON SALIVARY PARACETAMOL ELIMINATION
Authors: Madhusudanarao K. , Bapna J. S. , Adithan C. , Ray K. , Venkatadri N. , Kamatchi G. Lenin , Seetharaman M. L. , Bahadur P. 
Published: June 2007

SUMMARY1. Salivary elimination of paracetamol was studied in six male pulmonary tuberculosis patients on short course chemotherapy.2. Peak paracetamol concentration showed a steady decrease at the end of first week and continued until the end of the study.3. The elimination half‐life of paracetamol decreased 5 weeks after the therapy with a corresponding increase in the clearance rate.4. Adjustment of dosage of drugs that are metabolized by the microsomal enzymes may be required in patients on anti‐tubercular drug regimen in which rifampicin is included.
α1‐ AND α2‐ADRENOCEPTORS OF THE CIRCULAR MYOMETRIUM FROM THE DIOESTROUS GUINEA‐PIG
Authors: Haynes John , Pennefather Jocelyn N. 
Published: June 2007

SUMMARY1. In order to investigate the nature of the α‐adrenoceptors mediating contraction of circular myomctrium from dioestrous guinea‐pigs, the effects of several adrenoceptor antagonists upon log concentration curves to noradrenaline and phenylephrine have been examined.2. In the presence of ICI 118,551 and nisoxetine both phenylephrine and noradrenaline produced concentration‐dependent contractures of circular myometrium from virgin dioestrous guinea‐pigs. Noradrenaline was the more potent and produced larger maximal contractions. Indomethacin (1 μmol/l) decreased the maximum effects of phenylephrine but not those of noradrenaline. Xylazine produced indomelhacin‐sensitive contractions which were not dose‐related and which never exceeded 40% of those evoked by noradrenaline. Responses to xylazine and to noradrenaline, but not those to phenylephrine, were reduced in a low calcium solution.3. Prazosin produced competitive antagonism of the effects of phenylephrine upon preparations of circular myometrium from virgin and parous dioestrous animals; pA2 values were both 8.1. Phentolamine also competitively antagonized the effects of phenylephrine (virgin animals, pA2= 7.7).4. Both prazosin and phentolamine antagonized the effects of noradrenaline upon preparations from virgin dioestrous animals, however, Schild plot analysis did not indicate a simple bimolecular interaction between agonist and receptors. In the presence of prazosin the α2‐adrenoceptor antagonist idazoxan produced dose‐dependent parallel shifts in the positions of the log concentration‐response curves to noradrenaline; the pA2 was 7.7. In the presence of idazoxan or of indomethacin prazosin competitively antagonized the effects of noradrenaline; the pA2 values were 8.5 and 8.2 respectively.5. The present findings indicate that the effects of noradrenaline upon the contractility of the circular myometrium of dioestrous guinea‐pigs may result from activation of both α1‐ and α2‐adrenoceptors.
RENAL EFFECTS OF ATRIAL NATRIURETIC FACTOR (99–126) IN POTASSIUM LOADED SHEEP
Authors: Yates N. A. , Coghlan J. P. , Scoggins B. A. , McDougall J. G. 
Published: June 2007

SUMMARY1. The renal response to renal arterial infusion of synthetic atrial natriuretic factor (ANF 99–126) was examined in conscious sheep following dietary K loading, and compared with the response in normal sheep.2. Renal arterial infusion of ANF in K loaded sheep increased the excretion of Na and Ca, but did not affect the excretion of K.3. The natriuretic effect of ANF was attenuated in K loaded animals, possibly as a consequence of the reduction in Na status which is associated with K loading.