bluuebunny/crossref_metadata_2025_split huggingface dataset:
INFLUENCE OF ANTI‐HYPERTENSIVE DRUG TREATMENT ON VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: HAMILTON T.C. 
Published: July 2012

The effect of prolonged anti‐hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH‐rats), and of age‐matched normotensive Sprague‐Dawley rats was determined during the development of hypertension in SH‐rats and in the early stages of established hypertension. A comparison of the vascular reactivity to noradrenaline (NA) and 5‐hydroxytryptamine (5‐HT) was also made in isolated perfused mesenteric artery preparations from treated and control SH‐ and Sprague‐Dawley rats.
Chronic treatment from age 4 to 16 weeks with hydrallazine alone, or a combination of hydrallazine/hydrochlorothiazide/reserpine, ad libitum in the drinking water, prevented the development of hypertension in SH‐rats and also reduced the vascular reactivity to NA and 5‐HT in isolated vessel preparations from treated compared to control rats.
Similar drug treatments started in early established hypertension reduced blood pressure in SH‐rats over the 12 week treatment period (from age 8 to 20 weeks) without affecting vascular reactivity to NA and 5‐HT in the isolated vessel preparation.
Drug treatments had little effect on blood pressure of age‐matched Sprague‐Dawley rats and no effect on vascular reactivity to NA and 5‐HT in the isolated perfused mesenteric artery preparation from treated compared to control rats.
These results indicate that the development of increased vascular reactivity and of hypertension in SH‐rats occurs simultaneously and, therefore, the vascular changes may be a consequence of the structural changes induced by the raised blood pressure.
In established hypertension, no regression of vascular changes was observed despite prolonged reduction of blood pressure. The rǒle of an increased vascular reactivity in the maintenance of hypertension is therefore questionable.
AN INCREASED REACTIVITY IN HYPERTENSIVE RATS UNAFFECTED BY PROLONGED ANTIHYPERTENSIVE THERAPY
Authors: FINCH L. 
Published: July 2012

Isolated perfused mesenteric arteries obtained from chronic experimental hypertensive rats (deoxycorticosterone/NaCl) exhibited an increased reactivity to noradrenaline, 5‐hydroxytryptamine and adenosine 5′‐triphosphate (ATP) when compared with similar preparations from age‐matched normotensive animals.
The dose‐response curves to all three vasoconstrictor agents obtained from hypertensive animals exhibited a steeper slope, and higher maximum without any significant change in the threshold dose suggesting that adaptive/structural changes in the blood vessels had taken place.
Ten week treatments with antihypertensive combinations of hydrallazine, hydrochlorothiazide and reserpine or hydrallazine and mecamylamine lowered the systolic blood pressures of the hypertensive rats to those of normotensive animals and also reversed secondary changes such as periarteritis nodosa of the mesentery and cardiac hypertrophy.
The reactivity of these blood vessels to all these vasoconstrictor agents from the hypertensive rats with a normalized blood pressure was similar to those obtained with untreated hypertensive animals.
The persistent increased reactivity in the hypertensive rats after long‐term anti‐hypertensive treatment suggests that the hyperresponsiveness is secondary to the elevated blood pressures and that the adaptive/structural changes of the blood vessels in chronic hypertensive rats cannot be reversed by prolonged antihypertensive therapy.
RELEASE OF PROSTAGLANDIN‐LIKE SUBSTANCES BY SHIGELLA ENDOTOXIN AND ITS INHIBITION BY NON‐STEROIDAL ANTI‐INFLAMMATORY COMPOUNDS
Authors: BHATTACHERJEE P. 
Published: July 2012

The effects of intravenous and intraocular injections of Shigella endotoxin on the inflammatory response, the release of prostaglandin‐like substances into the aqueous humour, and the effects of indomethacin on the inflammatory response were studied in the rabbit eye.
Both intravenous and intraocular injection of endotoxin released 12.8 ng to 72 ng of prostaglandin‐like substances per ml of aqueous humour and increased the permeability of the blood‐aqueous barrier as shown by the rise in aqueous humour protein (26–52 mg protein/ml of aqueous humour).
Indomethacin, 0.25% administered topically completely inhibited the release of prostaglandin‐like substances but was found to have inconsistent inhibitory effects on the clinical signs of inflammation and on the blood‐aqueous barrier. Indomethacin was less effective in eyes receiving the higher dose of endotoxin.
It is suggested that prostaglandins and possibly other chemical mediators are involved in endotoxin‐induced ocular inflammation.
SODIUM AND CALCIUM IONS IN THE CONTROL OF TEMPERATURE SET‐POINT IN THE PIGEON
Authors: SAXENA P.N. 
Published: July 2012

The effect of altering the ionic balance of the cerebrospinal fluid (CSF) on cloacal temperature of unanaesthetized pigeons kept at room temperature (20–25°C) was examined by injection or infusion of solutions of different ionic composition into a cannulated lateral cerebral ventricle.
An increase in the concentration of calcium ions caused a fall in temperature and behavioural sedation. The effects were the same whether the calcium was present as calcium chloride or as the calcium disodium salt of ethylenediamine tetra‐acetic acid (CaNa2EDTA).
When the concentration of sodium ions in the CSF perfusate was increased by addition of NaCl or that of calcium ions was decreased by addition of Na2EDTA a rise in temperature was often produced but this was not consistent. NaCl sometimes had either no effect or lowered the temperature. Na2EDTA while producing a rise when first injected failed to do so when repeated a few hours, 24 h and often 72 h later. Prolonged infusion of either agent caused intense behavioural excitement leading to death.
Potassium ions, like sodium ions, caused a rise in temperature but only when infused continuously. Behavioural excitement was only rarely observed.
Magnesium produced a fall in temperature. The concentration required was much higher than that of calcium but the hypothermia was more prolonged suggesting a slower elimination of the magnesium ions from the CSF. Magnesium ions caused tremors, nystagmus and ataxia as opposed to sedation caused by calcium.
All these were central effects as they were not obtained when the substances were injected intravenously.
Since changes in body temperature of the pigeon produced by injection of calcium or sodium ions into the CSF were similar to those seen in various species of mammal, it is concluded that the relative concentration of these ions within the brain plays an important role in establishing the temperature set‐point in both birds and mammals.
SHAPE CHANGE AND AGGREGATION OF BLOOD PLATELETS: INTERACTION BETWEEN THE EFFECTS OF ADENOSINE DIPHOSPHATE, 5‐HYDROXYTRYPTAMINE AND ADRENALINE
Authors: MICHAL F. , MOTAMED MINA 
Published: July 2012

The interaction of effects between 5‐hydroxytryptamine (5‐HT) and adenosine diphosphate (ADP) on human or rabbit platelets was investigated in vitro. The initial platelet shape change and their aggregation were measured in stirred, citrated platelet‐rich plasma (PRP) at 37°C by recording the rate and extent of changes in light scattering and light transmission.
Both the velocity and extent of aggregation and the velocity and extent of the rapid morphological change caused by ADP were enhanced by simultaneous addition of 5‐HT. Methysergide but not imipramine inhibited the 5‐HT effects.
Platelets were made refractory to the aggregating and shape changing effect of either ADP or 5‐HT by repeated aggregation with the particular agent; platelets made refractory to ADP retained their responsiveness to 5‐HT and platelets made refractory to 5‐HT responded to ADP. Platelets pre‐incubated for 3–10 min with 5‐HT without aggregation showed greatly reduced aggregation on subsequent addition of ADP. Methysergide inhibited all the effects of 5‐HT whilst imipramine was inactive.
When the shape change or aggregation of platelets induced by ADP was submaximal, addition of 5‐HT increased it further. Pre‐incubation of PRP with 5‐HT before the addition of ADP resulted in failure of the secondary induction of aggregation or shape change by 5‐HT. The secondary induction by 5‐HT also did not occur in the presence of methysergide; imipramine had no inhibitory effect. Similar secondary induction of aggregation was shown by adrenaline injected during aggregation by ADP; the adrenaline effect was removed by phentolamine but not by propranolol.
Our results show that the initial change in shape of platelets and their aggregation can be induced by ADP or 5‐HT in specific manner. The interaction of the effect of these substances on platelets can result in either increase in platelet sensitivity or, under certain conditions, decrease in platelet responsiveness. The increase or depression of platelet reactivity appears to be a highly specific effect and is probably mediated at specific receptors involved with platelet activation.
IMPAIRED ABSORPTION OF CHLORPROMAZINE IN RATS GIVEN TRIHEXYPHENIDYL
Authors: RIVERA‐CALIMLIM LEONOR 
Published: July 2012

The absorption and tissue distribution of orally administered [14C]‐chlorpromazine (CPZ) were compared in trihexyphenidyl (THP; Artane)‐treated and control rats.
Total radioactivity (CPZ) in the plasma and brain of rats treated with THP was significantly lower whereas total radioactivity in the stomach was significantly higher than in rats not previously treated with THP.
Gastric emptying in rats treated with THP was significantly delayed as measured by gastric clearance of a marker, [14C]‐polyethylene glycol.
Transport of [14C]‐CPZ in everted sacs was not affected by treatment with THP.
Metabolism of [14C]‐CPZ by liver homogenates was not affected by treatment with THP.
The relationship of delayed gastric emptying in THP‐treated rats and their lower plasma and brain levels of [14C]‐CPZ after oral administration is discussed.
STUDIES ON THE RELATIVE EFFECTS OF PROSTAGLANDINS, BRADYKININ, 5‐HYDROXYTRYPTAMINE AND HISTAMINE ON THE SYNOVIAL MICROCIRCULATION IN DOGS
Authors: DICK W.C. , GRENNAN D.M. , ZEITLIN I.J. 
Published: July 2012

The relative effects of prostaglandins E1, E2, F1α, F2α, bradykinin, histamine and 5‐hydroxytryptamine (5‐HT) on the canine synovial microcirculation were investigated using the rate of clearance of radioactive xenon (133Xe) as an index of synovial perfusion.
All the compounds tested, except prostaglandin F1α, produced a vasodilator effect. The descending order of potency of the active compounds was (i) prostaglandin E1, (ii) prostaglandin E2 and bradykinin, (iii) histamine and 5‐HT, (iv) prostaglandin F2α. The most potent compound tested, prostaglandin E1 produced an effect in nanogram amounts in each joint.
Prostaglandin F2α has been reported to have an anti‐inflammatory action; however no evidence was found of antagonism of prostaglandin E1 by two dose levels of prostaglandin F2α.
Preliminary studies showed that threshold doses of prostaglandin E1 did not potentiate the vasodilator action of threshold or sub‐threshold doses of bradykinin in the dog synovium.
INVESTIGATION OF OCCURRENCE OF TOLERANCE TO BRONCHODILATOR DRUGS IN CHRONICALLY PRETREATED GUINEA‐PIGS
Authors: ANDERSON A.A. , LEES G.M. 
Published: July 2012

The actions of sympathomimetic amines on isolated preparations of atria, trachea and ileum were studied in vitro in guinea‐pigs, which had been pretreated for 5 or 12 days, by subcutaneous injection, with adrenaline (5 μg/kg), salbutamol (0.5 μg/kg), methoxamine (250 μg/kg) or saline (0.9% w/v NaCl solution).
In the trachea, a decrease in sensitivity (tolerance) to the relaxant effect of adrenaline was induced by pretreatment, for 12 but not for 5 days, with adrenaline. In these animals, cross‐tolerance to isoprenaline or salbutamol was not observed. Tolerance to the relaxant actions of adrenaline, isoprenaline or salbutamol was not observed after pretreatment with salbutamol.
In the trachea, pretreatment with methoxamine or adrenaline for 12 days did not change the sensitivity to the α‐adrenoceptor‐mediated contractor action of methoxamine.
In the atria from those guinea‐pigs pretreated with adrenaline or salbutamol, there was no reduced sensitivity to the β‐adrenoceptor agonist actions of adrenaline, isoprenaline or salbutamol. In animals pretreated with methoxamine or adrenaline, there was no observable tolerance or cross tolerance to methoxamine with respect to its α‐adrenoceptor‐mediated positive inotropic action in the atria and no unequivocal evidence of a reduced sensitivity to that action of adrenaline.
It was confirmed that the twitch‐like contractions of the longitudinal muscle of the electrically stimulated ileum were inhibited by sympathomimetic amines acting on α‐ and β‐adrenoceptors. There was no reduced sensitivity to the inhibitory actions of noradrenaline or isoprenaline on the twitch of ileum isolated from animals pretreated with adrenaline, salbutamol or methoxamine for 5 or 12 days.
From our results on these three preparations from the same animals, it is concluded that generalizations regarding changes in sensitivity to sympathomimetic amines following their prolonged administration should not be made in any one species.
HYPOTHERMIC ACTION OF CHLORPROMAZINE IN MONKEYS
Authors: CHAI C.Y. , FANN Y.D. , LIN M.T. 
Published: July 2012

In the conscious monkey (Macaca cyclopis) intravenous administration of chlorpromazine 0.1–8.0 mg/kg produced a fall of rectal temperature of 0.3 to 3.5°C after a latency of 3.5 to 10.8 minutes. The course of hypothermia lasted from 125 to 600 min or more.
Direct injection of chlorpromazine 100–800 μg into the lateral or fourth cerebral ventricle produced a similar fall of 0.3 to 2.0°C but with shorter latency (2 to 3.5 min) and with a duration of 94 to 375 minutes.
Two distinct structures in the brain stem, namely, the preoptic anterior hypothalamus (POAH) and medulla oblongata, responded to direct injection of chlorpromazine 200 μg. The sensitivity was slightly higher in the POAH than in the medulla. Structures in between were not sensitive.
The results suggest that chlorpromazine works principally through the central nervous system, i.e. the POAH and medulla oblongata, to mediate its hypothermic effect.
PROSTAGLANDIN ANTAGONISM BY SODIUM p‐BENZYL‐4‐[1‐OXO‐2‐(4‐CHLOROBENZYL)‐3‐PHENYLPROPYL]PHENYL PHOSPHONATE (N‐O164)
Authors: EAKINS K.E. , RAJADHYAKSHA V. , SCHROER R. 
Published: July 2012

The ability of sodium p‐benzyl‐4‐[1‐oxo‐2‐(4‐chlorobenzyl)‐3‐phenylpropyl]phenyl phosphonate (N‐0164) to antagonize contractions produced by prostaglandins E2 and F2α on isolated preparations of gerbil, rat and guinea‐pig gastrointestinal muscle has been studied.
N‐0164 was found to be a potent, partially selective prostaglandin antagonist in these isolated smooth muscle preparations. The blockade produced by N‐0164 in the isolated stomach strip of the rat had some, but not all, the characteristics of a competitive antagonism.
N‐0164 produced a dose‐dependent decrease in tone in the rat stomach strip that was abolished by pretreatment of the preparation with indomethacin.
N‐0164 prevented diarrhoea induced by prostaglandin E2 in mice when given by intraperitoneal injection but was less effective when given orally.
N‐0164 inhibited oedema induced with croton‐oil and pyridine‐ether in the mouse ear.
N‐0164 delayed the onset of erythema following ultraviolet irradiation of guinea‐pig skin only when an equimolar amount of pralidoxime chloride was added to the vehicle.
It is concluded that N‐0164 is a potent, partially selective prostaglandin antagonist on several isolated smooth muscle preparations. N‐0164 exhibits activity in vivo particularly following local application when problems associated with penetration and distribution are minimized.
ANALGESIA PRODUCED BY MORPHINE WHEN ACTING FROM THE LIQUOR SPACE
Authors: DEY P.K. , FELDBERG W. 
Published: July 2012

In cats analgesia was produced by morphine sulphate introduced into different parts of the liquor space in doses too small to be effective on intravenous injection. Analgesia was measured with the tail pinch method of Russell & Tate (1975).
On infusion into the fourth ventricle or into the subarachnoid space beneath the ventral surface of the brain stem caudal to the pons, doses of 100 to 200 μg of morphine sulphate were sufficient to produce strong long‐lasting analgesia. On injection into the cisterna magna somewhat larger doses (400 to 800 μg) were required.
It is concluded that the site where morphine acts when producing analgesia in all three circumstances is at the ventral surface of the brain stem.
The possibility is discussed that the structures acted upon are tryptaminergic nerve fibres. They arise from the raphe nuclei, belong to a descending inhibitory pathway, and on their way to the spinal cord, reach the ventral surface of the brain stem lateral to each pyramid, where they could be reached and acted upon by the morphine. This theory postulates a morphine sensitivity of tryptaminergic nerve fibres.
VASCULAR REACTIVITY OF PERFUSED VASCULAR BED IN SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: BHATTACHARYA B.K. , DADKAR N.K. , DOHADWALLA A.N. 
Published: July 2012

1Hypertensive and normotensive rats of the same age group were isolated from an inbred colony of spontaneously hypertensive rats.2The perfused hindquarter and mesenteric artery preparations obtained from hypertensive and normotensive rats exhibited an increased reactivity to noradrenaline (NA) and angiotensin II.3Dose‐response curves to NA obtained from hypertensive and normotensive rats exhibited a steeper slope and higher maximum than those from control rats.4These findings suggest that increased vascular reactivity of blood vessels is independent of the development or maintenance of elevated blood pressure.
THE EFFECTS OF INTRAPORTAL INJECTIONS OF NORADRENALINE, ADRENALINE, VASOPRESSIN AND ANGIOTENSIN ON THE HEPATIC PORTAL VASCULAR BED OF THE DOG: MARKED TACHYPHYLAXIS TO ANGIOTENSIN
Authors: RICHARDSON P.D.I. , WITHRINGTON P.G. 
Published: July 2012

1The hepatic portal vein of the anaesthetized dog was cannulated and perfused with blood derived from the cannulated superior mesenteric vein.2The portal vein was perfused at constant flow, the hepatic portal venous pressure being monitored continuously together with the inferior vena caval pressure. From these measurements, the hepatic portal venous vascular resistance was calculated.3Noradrenaline and adrenaline were injected intraportally in graded doses which caused dose‐dependent increases in the hepatic portal vascular resistance. At all doses, adrenaline was significantly (P<0.05) more potent than noradrenaline.4Intraportal injections of vasopressin caused reductions in calculated hepatic portal venous vascular resistance in most experiments; these effects were dose‐dependent.5No tachyphylaxis to the effects of noradrenaline, adrenaline or vasopressin was observed.6Intraportal injections of angiotensin caused dose‐dependent increases in calculated hepatic portal vascular resistance up to 5 μg; thereafter larger doses caused smaller increases in portal resistance.7Repeated intraportal injections of angiotensin revealed the existence of tachyphylaxis in the hepatic portal vascular bed.8Intraportal infusions of angiotensin caused rises in calculated hepatic portal vascular resistance from which there was almost complete ‘escape’ despite the continued infusions. Infusions of noradrenaline which caused similar rises in calculated portal vascular resistance did not exhibit equivalent degrees of ‘escape’.9The development of tachyphylaxis explains the fact that doses of 10 and 20 μg of angiotensin injected after 5 μg doses produced smaller effects. If a much longer time interval was allowed between injections (30 min), the dose‐response curve to angiotensin had a sigmoid shape.10These findings are discussed with respect to their possible importance in the functional status of the hepatic portal vascular bed in this species.
THE HAEMODYNAMIC AND METABOLIC EFFECTS OF MG 8926, A PROSPECTIVE ANTIDYSRHYTHMIC AND ANTIANGINAL AGENT
Authors: MARSHALL R.J. , PARRATT J.R. 
Published: July 2012

1The antidysrhythmic, haemodynamic and metabolic effects of a new prospective antianginal and antidysrhythmic agent, N‐(3,3‐diphenylpropyl)‐α‐methyl‐β‐cyclohexylethylamine hydrochloride (MG 8926), have been compared with the chemically related substance, prenylamine, in anaesthetized greyhounds and guinea‐pigs.2When given intravenously 20 min beforehand, both MG 8926 and prenylamine (5 mg/kg) significantly suppressed the early dysrhythmias induced by coronary artery ligation in anaesthetized greyhounds. At a dose of 1 mg/kg, MG 8926 also protected anaesthetized guinea‐pigs from dysrhythmias induced by ouabain infusions.3In dogs pretreated with MG 8926, metabolic changes indicative of myocardial ischaemia (increased Pco2 and potassium efflux, decreased oxygen content and pH) were less marked than those occurring in control animals.4Evidence was obtained that MG 8926, when given either before or after coronary occlusion, was capable of decreasing the severity of myocardial ischaemia as assessed by ST‐segment changes in epicardial electrocardiograms.
THE β‐ADRENOCEPTOR STIMULANT PROPERTIES OF OPC‐2009 ON GUINEA‐PIG ISOLATED TRACHEAL, RIGHT ATRIAL AND LEFT ATRIAL PREPARATIONS
Authors: YABUUCHI Y. 
Published: July 2012

The β‐adrenoceptor stimulant properties of 5‐(1‐hydroxy‐2‐isopropylaminobutyl)‐8‐hydroxycarbostyril hydrochloride hemihydrate (OPC‐2009) were compared with those of isoprenaline and salbutamol on guinea‐pig isolated tissues.
In producing tracheal relaxation, OPC‐2009 was approximately 7 times more potent and salbutamol 5 times less potent than isoprenaline. Both compounds were less potent than isoprenaline in increasing either the rate of beating of isolated right atria or the contractile force of left atria, OPC‐2009 being 4 and 127 times and salbutamol being 100 and 700 times less potent on the respective preparations.
Selectivity calculated from EC50 ratio indicates that OPC‐2009 was approximately 26 times and salbutamol approximately 21 times more selective than isoprenaline for tracheal smooth muscle as compared to right atrial muscle, whereas OPC‐2009 was approximately 850 times and salbutamol 140 times more selective than isoprenaline for tracheal smooth muscle as compared to left atria.
The responses to OPC‐2009 on trachea and right atria were not altered by treatment of animals with reserpine 24 h previously. Propranolol was a competitive antagonist of OPC‐2009 on these tissues.
OPC‐2009 at high concentrations competitively antagonized the positive chronotropic and inotropic responses to isoprenaline, indicating that OPC‐2009 like salbutamol, may be classified as a partial agonist.
The results indicate that the action of OPC‐2009 is more selective for tracheal smooth muscle than cardiac muscle and are interpreted in the light of subdivisions of β‐adrenoceptors.
RELAXATION OF SMOOTH MUSCLE FOLLOWING CONTRACTION ELICITED BY SYMPATHETIC NERVE STIMULATION in vivo
Authors: ECCLES R. , MacLEAN A.G. 
Published: July 2012

A method for studying in vivo the process of neuroeffector transmission in the nictitating membrane and nasal blood vessels of the cat is described.
Administration of desmethylimipramine or cocaine caused increases in both the amplitude and duration of the nasal and membrane responses which may be explained by inhibition of neuronal uptake of noradrenaline.
Phenoxybenzamine depressed the responses to nerve stimulation, but had little effect on the relationship between response amplitude and rate of recovery.
The relationship between response amplitude and rate of recovery is discussed and related to the sigmoid shape of a log concentration‐response curve.