bluuebunny/crossref_metadata_2025 huggingface dataset:
THE CONTRACTION INDUCED BY CALCIUM IONS IN ISOLATED GUINEA‐PIG VAS DEFERENS
Authors: Sugjmoto J. , Furumichi A. , Murakami M.
Published: June 2007

1. When isolated guinea‐pig vas deferens was pretreated with 0.01% sodium edetate in an isotonic sucrose medium and then transferred to an edetate‐free sucrose medium, the addition of CaCl2 (1.1 to 35.2 mmol/1) induced a contraction.

2. The contraction was greatest when the CaCl2 was added soon after pretreat‐ment with edetate, and decreased with increasing time, almost disappearing after 1h.

3. When KC1 (1.4 to 22.4 mmol/1) was added in place of CaCl2, the contraction was lowest soon after pretreatment with edetate, and increased with time; after 1 h, the effect was 80.7% of that observed in a preparation that had not been pretreated with edetate.
THROMBOXANE B2 INHIBITS PROSTAGLANDIN E2 INACTIVATION BY THE RAT ISOLATED PERFUSED LUNG
Authors: Boura A. L. A. , Murphy R. D.
Published: June 2007

1. The effect of thromboxane B2 (T×B2) on inactivation of prostaglandin E2 (PGE2) by the rat isolated perfused lung has been studied.

2. TxB2 when infused in low concentrations (100 ng/ml) into the pulmonary artery reduced PGE2 inactivation approximately two‐fold.

3. The rat isolated fundus strip was contracted by higher concentrations of TxB2 (1.0 Mg/ml) in the presence of hyoscine, mepyramine, methysergide, phenoxy‐benzamine and propranolol. The size of contraction was reduced by indomethacin in concentrations known to inhibit prostaglandin synthetase.

4. Thus, in circumstances in which T×B2 and PGE2 are released concomitantly by the lung, low concentrations of TxB2 may augment PGE2 release by reducing its inactivation.
AGONISTIC AND ANTAGONISTIC ACTIONS OF 3,4‐DmYDROXY‐SUBSTITUTED PHENOXYPROPANOLAMINES DM GUINEA‐PIG ATRIA AND TRACHEA
Authors: Keh G. S. , Raper C. , Dowd H.
Published: June 2007

1. Racemic mixtures of noradrenaline, adrenaline, isoprenaline, N‐r‐butylnor‐adrenaline and their corresponding derivatives containing an oxymethylene (OM) link between the phenyl ring and ethanolamine side‐chain have been tested for their effects on β‐adrenoceptors in isolated guinea‐pig atrial and tracheal preparations.

2.In atrial and in spontaneously contracted tracheal preparations both the parent catecholamines and their corresponding OM‐derivatives had a similar order of potency as 0‐receptor agonists.

3.In carbachol‐stimulated tracheal preparations the OM‐derivatives were shown to have partial agonistic actions.

4.As in other phenylethanolamines and phenoxypropanolamines, both the agonistic and antagonistic potency of the OM‐derivatives increased with increasing amine substitution.
ALTERATIONS EM LEVELS OF VASCULAR HISTAMINE IN THE DOCA‐HYPERTENSIVE RAT
Authors: Holcslaw T. L. , Imhoff L.
Published: June 2007

1. Histamine was detected in the abdominal aorta and the femoral arteries of normotensive and also DOCA‐hypertensive rats.

2. Levels of total histamine (mast cell and non‐mast cell histamine) were significantly reduced in both abdominal aorta and the femoral artery of the DOCA‐hypertensive rats, relative to the normotensive controls.

3. It is suggested that the diminished level of vascular histamine may be related to the development and/or maintenance of the hypertensive state and is also related to the reduced magnitude of active reflex vasodilatation.
CONVERSION OF ANGIOTENSIN I TO ANGIOTENSIN II IN SHEEP
Authors: Fernley R. T. , Coghlan J. P. , Cran E. J. , Fei T. W. , Scoggins B. A. , McGregor A.
Published: June 2007

1. The methodology for measurement of angiotensin I in whole blood is described.

2. Angiotensin I was measured in arterial and venous blood samples from sodium‐loaded, sodium‐replete and sodium‐depleted sheep. Venous blood concentrations were higher than arterial angiotensin I concentrations. Arterial angiotensin I concentrations increased with increasing sodium deficiency.

3. Angiotensin II was infused into six sodium‐replete sheep, the blood concentrations of angiotensin II measured and the metabolic clearance rates calculated. The average value was 121 ± 21 1/h.

4. Angiotensin I was then infused into these sheep and arterial and venous blood concentrations of angiotensins I and II determined. From this data and the metabolic clearance rate of angiotensin II, the degree of conversion of angiotensin I to II was calculated. The values varied in different sheep from 54 ± 2% to 105 ± 6% (n= 6).
EFFECT OF SOME PROSTAGLANDIN SYNTHESIS INHIBITORS ON THE ANTINOCICEPTIVE ACTION OF MORPHINE IN ALBINO RATS
Authors: Srivastava D. N. , Bhattacharya S. K. , Sanyal A. K.
Published: June 2007

1. Five prostaglandin synthesis inhibitors, indomethacin, diclofenac, mefenamic acid, ibufen and paracetamol, were found to inhibit the antinociceptive action of morphine without affecting the antinociceptive response of an equi‐analgesic dose of prostaglandin E1

2. Diclofenac was found to be the most potent and longest acting, whereas paracetamol was the least potent and shortest acting. Indomethacin, mefenamic acid and ibufen occupied an intermediate position, both in potency and duration of action.

3. The results suggest that prostaglandins may be involved in the antinociceptive action of morphine in albino rats.
THE EFFECT OF PRAZOSIN ON PRE‐ AND POSTSYNAPTIC α‐RECEPTORS IN THE PITHED RAT
Authors: Hua A. S. P. , Moulds R. F. W.
Published: June 2007

1. Prazosin had a marked inhibitory effect on post‐synaptic a‐receptors in the pithed rat, as measured by the blood pressure response to the cumulative administration of clonidine.

2. Prazosin had no inhibitory effect, however, on the pre‐synaptic a‐receptor, as measured by the clonidine‐induced reduction in the tachycardia produced by stimulation of the cardiac nerves.

3. These results suggest that prazosin has a selective antagonistic affinity for post‐synaptic a‐receptors.
LACK OF EFFECT OF BROMOCRIPTINE ON SERUM LEVELS OF CALCIUM IN THE RAT
Authors: Tan C. M. , Tan G. J. S.
Published: June 2007

1. The effect of bromocriptine (a prolactin suppressant drug) on the serum levels of calcium was studied in the male rat. The drug was administered subcutaneously at a dosage of 100μg per 100 g body weight three times per day.

2. Chronic treatment with bromocriptine had no significant effect on the serum calcium levels. It appears that neither bromocriptine per se nor normal circulating prolactin levels exert any significant influence on blood calcium homeostasis.
THE ANTAGONISM BY PROPRANOLOL AND α‐METHYLPROPRANOLOL (ICI 77602) OF VASCULAR AND CARDIAC RESPONSES TO ISOPRENALINE IN ANAESTHETIZED DOGS
Authors: Fitzgerald J. D. , O'Donnell Stella R.
Published: June 2007

1. In anaesthetized dogs, α‐methylpropranolol was less potent than propranolol in antagonizing both vascular (hind limb perfusion pressure) and cardiac heart rate) responses to isoprenaline.

2. α‐Methylpropranolol was more potent in antagonizing vascular than cardiac responses to isoprenaline, but this selectivity was no greater than that seen also with propranolol.

3. Isoprenaline sensitivity was greater in the hind limb than the heart and vascular‐selective antagonism was more pronounced in those dogs in which this differential sensitivity was the greatest.

4. Introduction of an a‐methyl group into propranolol decreases its 0‐adrenoceptor antagonist potency but does not enhance vascular selectivity.
COMPARISON OF THE ANORECTIC AND MOTOR ACTIVITY EFFECTS OF SOME AMINOINDANES, 2‐AMINOTETRALIN AND AMPHETAMINE IN THE RAT
Authors: Mrongovius R. I. , Bolt A. G. , Hellyer R. O.
Published: June 2007

1. The anorectic and motor activity effects of 1‐aminoindane, 2‐aminoindane, some N‐substituted 2‐aminoindanes,2‐aminotetralin, amphetamine and fenfluramine were determined in rats.

2. The two compounds with structures most like the extended conformation of amphetamine, 2‐aminotetralin and 2‐aminoindane, were potent anorectics. At dosages which halved the intake of food over 1 h, amphetamine increased motor activity, 2‐aminotetralin had no effect, and 2‐aminoindane reduced motor activity.’

3. Both the anorectic and central stimulant actions of 2‐aminoindane were absent in N‐ethyl‐ and N‐isopropyl‐2‐aminoindane.

4. 1‐Aminoindane, whose structure is like the folded conformation of amphetamine, produced a small anorectic effect and depressed motor activity.
INTERACTIONS BETWEEN METHAQUALONE AND ETHANOL IN RATS AND MICE DURING ACUTE AND CHRONIC STATES
Authors: Ho C. C. , Ho A. K. S.
Published: June 2007

1. The effects of acute and chronic treatment of methaqualone on ethanol preference, the rate of disappearance of ethanol and on toxicity were studied in mice and rats.

2. Acute treatment with methaqualone showed a dose‐dependent suppression in the voluntary intake of ethanol in C57B1/6J mice and rats. No significant change in ethanol intake was observed during chronic methaqualone treatment and withdrawal.

3. Methaqualone pretreatment significantly (P < 0.005) delayed the disappearance of ethanol in the blood and brain over a period of 50 to 200 min after a loading dose of 2.0 g/kg, i.p., of ethanol.

4. Methaqualone pretreatment at doses of 140 and 200 mg/kg significantly increased ethanol toxicity by 11% and 28%, respectively. Co‐administration of ethanol using 6.0, 7.0 and 8.0 g/kg also reduced the LD50 of methaqualone by 19%, 24% and 40%, respectively.

5. Chronic administration with ethanol decreased the toxicity due to methaqualone. Potentiation of ethanol toxicity by methaqualone may be of clinical importance in view of the narrow range of safety margin of ethanol.
BLOOD PRESSURE AND METABOLIC EFFECTS OF ACTH IN ANEPHRIC SHEEP
Authors: Fan J. S. K. , Coghlan J. P. , Denton D. A. , Scoggins B. A. , Whitworth Judith A.
Published: June 2007

1. ACTH (80–100 iu/day) was administered to seven sheep for 3–5 days following bilateral nephrectomy.

2. ACTH treatment produced rises in mean arterial pressure in anephric sheep similar to those observed in intact animals. Following withdrawal of ACTH, blood pressure declined over the following 72 h.

3. ACTH produced a transient fall in plasma potassium in anephric sheep, suggesting an internal redistribution mechanism for this ion.

4. These studies demonstrate that adrenal steroid hormones can modify blood pressure in the absence of the kidney.
HAEMODYNAMIC EFFECTS OF NICERGOLINE IN MAN AT REST AND DURING EXERCISE
Authors: Boismare F. , Lefrançois J.
Published: June 2007

1. The intravenous administration of nicergoline (5 mg) was followed by a rapid and sustained lowering of blood pressure; less rapid effects were bradycardia and an elevation of cardiac output. These delayed effects are consistent with an indirect action on the α‐adrenoreceptors of the central nervous system.

2. Following the oral administration of nicergoline (30 mg), a partial reduction of exercise‐induced lactacidaemia was demonstrated, which is consistent with the haemodynamic changes shown at rest.
TRITIUM EXCRETION AFTER INTRAVENOUS ADMINISTRATION OF TRITIUM LABELLED ADRENALINE AND NORADRENALINE AND DIGITAL VASCULAR REACTIVITY TO ADRENALINE AND NORADRENALINE IN NORMOTENSIVE AND LABILE HYPERTENSIVE SUBJECTS
Authors: Guia Daisy De , Mendlowitz Milton , Vlachakis Nicolas D. , Gitlow Stanley E. , Nissenbaum Mark
Published: June 2007

1. The 24‐h urinary excretion of tritium after tritiated adrenaline administration and digital vascular reactivity to exogenously administered adrenaline and noradrenaline were measured in ten normotensive and in twenty‐eight labile essential hypertensive subjects. Tritiated noradrenaline excretion and apparent noradrenaline secretion rate were also measured in ten and eleven of these subjects, respectively.

2. Despite overlapping, the mean 24‐h tritium excretion after 3H‐adrenaline administration as well as reactivity to adrenaline were significantly greater in the hypertensive than in the normotensive subjects, whether or not they had increased responsiveness to noradrenaline. Significant correlation, however, was observed between tritium excretion of adrenaline and reactivity to adrenaline in both labile hypertensive and normotensive subjects. These measurements were also both significantly correlated with percentage variability in systolic and diastolic blood pressure in the labile hypertensive subjects.

3. No significant correlation was observed between adrenaline as against noradrenaline measurements, whether physiological or biochemical, in either hypertensive or normotensive subjects.
ARE NEURONAL UPTAKE MECHANISMS RESPONSIBLE FOR THE DIFFERENCE IN SENSITIVITY TO NORADRENALINE BETWEEN HUMAN ARTERIES AND VEINS?
Authors: Stevens M. J. , Moulds R. F. W.
Published: June 2007

1. The sensitivity of human metacarpal veins and digital arteries obtained post‐mortem to noradrenaline and phenylephrine has been tested.

2. pED50 values for noradrenaline were significantly higher in the veins (699, s.e.m. = 008) than in the arteries (6.56, s.e.m. = 009), whereas pED50 values for phenylephrine in the two tissues were not significantly different (arteries: 6.24, s.e.m. = 009; veins: 6.26, s.e.m. = 005).

3. The addition of propranolol (4 × 10−6 mol/l) alone, or in combination with hydrocortisone (4 × 10−5 mol/l), did not affect the responses to either noradrenaline or phenylephrine. The further addition of cocaine (3 × 10−5 mol/l) slightly shifted the noradrenaline and phenylephrine concentration‐effect curves to the left in both arteries and veins, but veins were still found to be more sensitive than arteries to noradrenaline whilst there was still no difference in the sensitivity of veins and arteries to phenylephrine.

4. Cocaine also slightly potentiated responses to barium chloride, potassium chloride and serotonin.

5. It is concluded that the difference in sensitivity to noradrenaline between arteries and veins cannot be explained by differences in neuronal uptake and it is possible that there may be differences in the properties of the postsynaptic α‐adrenoreceptors of the two tissues. It is also concluded that the potentiation of the contractile effect of noradrenaline produced by cocaine is not solely due to inhibition of neuronal uptake of amines.
COMPARISON OF HAEMODYNAMIC RESPONSES TO POSITIVE‐END‐EXPIRATORY VENTILATION AND PERICARDIAL EFFUSION IN DOGS
Authors: Rabkin Simon W. , Morris Andrew L. , Sharma Gyan P. , Ayotte Brian
Published: June 2007

1. The haemodynamic responses to progressive increments in positive end‐expiratory pressure ventilation (PEEP) were assessed in dogs in the presence and absence of pericardial effusion (2‐2 ml saline/kg).

2. Increasing levels of PEEP (0, 4, 8, 16 cm H2O) were associated with increases in right atrial, left atrial, pericardial and pulmonary artery diastolic pressure; increases in pulmonary vascular resistance; decreases in aortic blood pressure; and decreases in cardiac index or stroke index.

3. Pericardial effusion that was associated with an increase in pericardial pressure of 3 mmHg was not associated with significant changes in aortic blood pressure or stroke index. In contrast 8 cm PEEP was associated with significant decreases in both these haemodynamic variables yet pericardial pressure increased only 2‐2 mmHg.

4. For these levels of PEEP and pericardial effusion, the same haemodynamic response to PEEP was observed regardless of the presence or the absence of pericardial effusion.

5. Similar changes in aortic blood pressure and stroke index despite different pericardial pressures is reflected by significantly different intercepts in the linear model relating these haemodynamic variables to pericardial pressure in the presence and absence of pericardial effusion.

6. The results suggest that these haemodynamic consequences of PEEP are primarily a function of pulmonary hyperinflation and are less dependent on increases in extracardiac pressure per se.
FAILURE OF SUPPRESSION OF INTRARENAL ANGIOTENSIN II IN THE CONTRALATERAL KIDNEY OF ONE‐CLIP TWO‐KIDNEY HYPERTENSIVE RATS
Authors: Mendelsohn F. A. O.
Published: June 2007

1. Two‐kidney one‐clip hypertension was produced in rats by application of a 0‐20 mm clip to the left renal artery.

2. After three weeks, the animals had mildly elevated PRA, kidney renin was elevated in the clipped kidney and markedly suppressed in the contralateral kidney when compared to values in sham‐operated rats.

3. Intrarenal All was elevated in the clipped kidney either when compared to the contralateral kidney or to values in the controls. However, in the contralateral kidney, All was not different from controls.

4. Changes in intrarenal AH do not, therefore, always parallel those of renal renin. Failure of suppression of All in the contralateral kidney is likely to be of pathogenetic importance in development of hypertension in this experimental model.
THE EFFECT OF METOPROLOL AND ATENOLOL ON PLASMA HIGH DENSITY LIPOPROTEIN LEVELS IN MAN
Authors: England John D. F. , Simons Leon A. , Gibson Joyce C. , Carlton Michael
Published: June 2007

1. The effects of two β‐adrenoreceptor blocking drugs, metoprolol and atenolol, on plasma lipoproteins were studied in thirty‐four patients using a single‐blind cross‐over design, with a 10‐day placebo washout period between drugs.

2. Compared with placebo values, neither metoprolol nor atenolol influenced total plasma cholesterol levels, while total plasma triglycerides increased slightly.

3. Low density lipoprotein protein level remained unaltered, while high density lipoprotein (HDL) cholesterol and protein were significantly reduced by both β‐adrenoreceptor blockers.

4. The ratio of total cholesterol to HDL cholesterol was increased by both drugs.

5. The data suggest that patients taking these drugs over many years may be exposing themselves to increased vascular risk, despite other anticipated benefits from such therapy.
A METHOD OF DETERMINING INTRINSIC HEPATIC CLEARANCE FROM THE FIRST‐PASS EFFECT
Authors: Bass L. , Winkler K.
Published: June 2007

1. The relation between systemic hepatic clearance, intrinsic hepatic clearance and hepatic blood flow is considered from the point of view of the sinusoidal perfusion (parallel tube) model of the liver.

2. It is shown how intrinsic hepatic clearance may be calculated, for substrates eliminated in the liver and the kidney only, from data obtained by introducing successively an oral and an intravenous dose (i.e., by using the first‐pass effect) without the clinically cumbersome catheterization of the liver vein.

3. The rate of hepatic blood flow is shown to follow from the same data.
THE ACTION OF ASPIRIN ON PLASMA KININOGEN AND OTHER PLASMA PROTEINS IN RHEUMATOID PATIENTS: RELATIONSHIP TO DISEASE ACTIVITY
Authors: Sharma J. N. , Zeitlin I. J. , Brooks P. M. , Buchanan W. W. , Dick W. C.
Published: June 2007

1. When six female seropositive rheumatoid patients were given placebo therapy for 48 h, their mean plasma kininogen level, 9.2 ± 0.7 μg bradykinin equivalents (bk eq) per ml, was found to be 59% greater than that of a group of eight healthy female volunteers (5.8 ± 0.5 μg/ml).

2. When the rheumatoid patients received aspirin therapy for 1 week, their mean plasma kininogen concentration fell by 31% to 6.3 ± 0.8 μg Bk eq/ml. This was accompanied by a 20.4% fall in mean plasma α2‐globuKn level. Haematocrit and total plasma protein were not significantly altered (P > 0.05).

3. The fall in kininogen was very rapid, the main reduction occurring within the first hour.

4. Aspirin therapy greatly reduced the pain assessments but had no effect on plasma concentrations of IgG, IgA, IgM, complement component C3, nor on ESR, haemoglobin, leucocyte count, nor ring size. Left hand grip strength was increased while right hand grip strength was unchanged.

5. The action of aspirin on plasma kininogen and α2‐globulin was similar to that of indomethacin. Plasma kininogen has been considered to be an acute phase reactant. The possible diagnostic value of plasma kininogen estimation is discussed.
CHANGES IN PLASMA NORADRENALINE AND ADRENALINE DURING ISOMETRIC EXERCISE
Authors: Watson R. D. S. , Littler W. A. , Eriksson B‐M
Published: June 2007

1. Plasma noradrenaline and adrenaline were measured radioenzymatically in twelve hypertensive and four normotensive subjects before and during handgrip. In the resting arm (n= 11), plasma noradrenaline increased by 17% (P<0 01) and plasma adrenaline by 27% (P<0 01). In the exercising arm, plasma adrenaline increased by 97% (P< 0 005) but the mean increase of noradrenaline of 10% was not significant (P>0 1).

2. The noradrenaline response suggests a small and variable sympathetic adrenergic response; the significant difference (P<0 05) in adrenaline responses between resting and exercising arms may reflect local variation in tissue clearance.
ROUTE AND RATE OF HYDRALLAZINE ADMINISTRATION AS DETERMINANTS TO ITS HYPOTENSIVE EFFECT IN RABBITS
Authors: Talseth T. , McNay J. L. , Clementi W. A.
Published: June 2007

1. The cardiovascular responses to varying doses of hydralazine were studied in renal hypertensive rabbits.

2. The depressor effect of hydralazine was independent of the rate of its i.v. administration (bolus v. a 15 min constant infusion).

3. Intraperitoneally administered hydralazine was significantly less active than equimolar i.v. doses, and the relative potency (i.p. v. i.v.) did not increase with increasing doses.

4. In spite of inferential evidence to the contrary, we did not find any pharmacodynamic support for non‐linear processes being involved in metabolism of hydralazine.
DOES THE BARORECEPTOR‐HEART RATE REFLEX INDICATE THE CAPACITY OF THE ARTERIAL BARORECEPTORS TO CONTROL BLOOD PRESSURE?
Authors: Ludbrook J. , Mancia G. , Zanchetti A.
Published: June 2007

1. We have examined the question asked in the title by studying: the carotid baroreceptor reflex in man with a variable‐pressure neck chamber; the carotid baroreceptor reflex in conscious rabbits with a variable‐pressure capsule around the carotid bifurcation; and the baroreceptor‐heart rate reflex.

2. At rest, the association between the sensitivities of the carotid barorecep‐tor‐blood pressure and ‐heart rate reflexes, and of these with the baroreceptor‐heart rate reflex, is weak. Exercise causes dissociation between control of blood pressure and heart rate. In hypertension, depression of the baroreceptor‐heart rate reflex does not reflect the altered characteristics of the carotid sinus‐blood pressure reflex.
REDUCED RESPONSES TO NORADRENALINE OF ISOLATED DIGITAL ARTERIES FROM HYPERTENSIVES
Authors: Moulds Robert F. W.
Published: June 2007

1. Strips of digital arteries obtained post‐mortem from thirteen hypertensives have been compared with those from thirteen normotensives.

2. The strips from hypertensives and from males had a significantly greater response to 80 mmol/1 KCl, but this was due to the increased cross‐sectional areas of the strips from hypertensives and from males.

3. The maximum responses to noradrenaline and serotonin, but not the pED50 values, were significantly smaller in the strips from the hypertensives than in those from the normotensives, but there were no differences between the strips from hypertensives and normotensives in either the maximum response or pED50 values to angiotensin or barium chloride.

4. It is concluded that these results suggest a decreased number of α‐receptors are present in human hypertensive vascular smooth muscle and this is a sequel either of the increased pressure itself, or of increased exposure in vivo of the blood vessels from hypertensives to noradrenaline.
INCREASED SODIUM PERMEABILITY OF ERYTHROCYTES IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Wiley J. S. , Hutchinson J. S. , Mendelsohn F. A. O. , Doyle A. E.
Published: June 2007

1. The Na permeability of red cells from spontaneously hypertensive rats (SHR) has been studied. In the Japanese Wistar‐Kyoto strain, a significant increase of 30% in 22Na influx for male SHR was found compared with normotensive male controls. In contrast the Na influx for genetically hypertensive and normotensive New Zealand rats did not differ. Normotensive Wistar‐Kyoto rats rendered hypertensive by unilateral renal artery clipping, did not show any difference in Na influx from control animals.

2. These results suggest that the Japanese strain of SHR has a genetically determined increase in erythrocyte Na permeability.
THE EFFECTS OF MECLOFENAMATE ON RENAL AND PERIPHERAL VASCULAR BEDS IN CONSCIOUS RABBITS
Authors: Banks R. A. , Beilin L. H. , Soltys J. S.
Published: June 2007

1. Meclofenamate caused a dose‐dependent increase in renovascular resistance in conscious rabbits.

2. This effect was greatest in inner cortical zones at the highest dose (6 mg/kg) but at the lowest dose (0‐75 mg/kg) vascular resistance in the outer cortex was preferentially increased.

3. In contrast, meclofenamate increased cerebral perfusion and the proportion of cardiac output received by the testis. No effect was demonstrated on other organs studied.

4. The results suggest a local vasodilator influence of renal prostaglandins in normal conscious rabbits.
ASSESSMENT OF NEURONAL UPTAKE OF NORADRENALINE IN HUMANS: DEFECTIVE UPTAKE IN SOME PATIENTS WITH ESSENTIAL HYPERTENSION
Authors: Esler Murray , Leonard Paul , Kelleher Dianne , Jackman Graham , Bobik Alex , Skews Helen , Jennings Garry , Korner Paul
Published: June 2007

1. Disappearance of tritiated noradrenaline from plasma, after infusion to steady‐state, was studied to assess neuronal uptake of noradrenaline in essential hypertension.

2. Plasma tritiated noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed both in normal subjects after desipramine, and in patients with sympathetic nerve dysfunction (autonomic insufficiency).

3. In nine of thirty‐eight hypertensive patients the t1½ similarly was prolonged. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, was increased in these patients.

4. Defective neuronal uptake of noradrenaline, by exposing adrenergic receptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.
THE PATHO‐PHYSIOLOGY OF CHRONIC ARTERIAL HYPERTENSION: A HYPOTHESIS
Authors: Boyd G. W.
Published: June 2007

An important unresolved problem in hypertension is how an elevated blood pressure from any cause may eventually become self‐sustaining and apparently independent of the initiating event. Folkow has suggested that this results from arteriolar narrowing due to a physiological response or ‘structural adaptation’ to the higher pressure, but it is suggested here that the histological appearances within the arterioles in chronic hypertension are much more in keeping with a pathological process, and not vastly different from those observed after intimal damage to larger arteries in experimental atherosclerosis. From this, it is proposed that the arteriolar narrowing is secondary to the endothelial damage which arises when a maintained cardiac output is forced through a constricted arteriolar bed, so increasing substantially the shearing stress on their walls.
STIMULATION BY ANGIOTENSIN OF PROSTACYCLIN BIOSYNTHESIS IN RATS AND DOGS
Authors: Dusting G. J. , Mullins Elizabeth M.
Published: June 2007

1. Stimulation of prostanoid release by angiotensins (AI and All) in rat isolated mesenteric vasculature and in the circulation of anaesthetized dogs has been investigated by bioassay.

2. AI and All released a PGI2‐like substance into rat mesenteric effluent and arterial blood of dogs; PGE2, PGF2α or TXA2 were not detected.

3. AI stimulated PGL release in both systems largely as a result of its conversion to All, since PGI2 release was much reduced after treatment with captopril.

4. Intravenous AII (0‐2‐1.0μg kg−1min−1) in dogs released PGI2 mainly from the lungs since right atrial blood contained much less than arterial blood.

5. Indomethacin (1 μg/ml) abolished All‐induced PGI2 release from the mesentery preparation, but intravenous indomethacin (10 mg/kg), meclofena‐mate (2 mg/kg) or aspirin (100 mg/kg) did not eliminate the pulmonary source of PGI2 in dogs. These findings highlight the dangers of assuming in vivo treatment with cyclo‐oxygenase inhibitors abolishes biosynthesis of all prostanoids.
EFFECT OF β‐ADRENORECEPTOR BLOCKADE ON THE RENIN RESPONSE TO ACUTE NATRIURESIS
Authors: Vandongen Robert , Barden Anne , Tunney Anne
Published: June 2007

1. The response of plasma renin activity to frusemide 40 mg given intravenously, was examined before and after oral propranolol 160 mg daily for 7 days in normal and hypertensive subjects.

2. Although basal renin levels were often reduced, the increase following frusemide was essentially unaltered by propranolol therapy.

3. These findings indicate that enhanced renin activity associated with diuretic use may not be prevented by concurrent propranolol administration. Limitation of the hypotensive action of combined β‐blocker diuretic therapy can therefore be anticipated.

4. Preservation of the renin stimulatory effect of frusemide during beta blockade confirms the value of this procedure in the investigation of mineralo‐corticoid and renovascular hypertension where discontinuation of treatment may be undesirable.
EFFECTS OF MEXILETINE ON TRANSMEMBRANE ACTION POTENTIALS AS AFFECTED BY EXTERNAL POTASSIUM CONCENTRATION AND BY RATE OF STIMULATION IN GUINEA‐PIG PAPILLARY MUSCLES
Authors: Sada Hideaki , Ban Takashi , Oshita Shuzo
Published: June 2007

1. The effects of mexiletine and quinidine were compared on transmembrane potentials in guinea‐pig papillary muscles, using conventional microelectrode techniques.

2. Mexiletine (23–1 μ mol/1) decreased the maximum rate of rise of the action potential (V̇max) and increased the ratio of the effective refractory period to the action potential duration at 90% repolarization level (ERP/APD90); these effects were prominent with elevation of the external potassium concentration ([K]o) from 2–7 to 5–4, 81 and 100mmol/1.

3. The percentage decrease in V̇max induced by 5 and 10 μmol/1 of quinidine was approximately constant in 2–7, 5–4 and 100 mmol/1 [K]o solutions.

4. The decrease in V̇max produced by mexiletine was progressively increased as the driving rate was raised from 0–25 to 5H z. This rate‐dependent change was pronounced when the concentration was raised from 23–1 to 46–2 and 92–4 /μmol/1.

5. Mexiletine in concentrations of 23–1 and 92–4 μ miol/1 delayed the recovery of V̇max in a premature action potential to the level of V̇max in the conditioning action potentials at the driving rate of 0–25 Hz.

6. It appears that mexiletine exerts its anti‐arrhythmic action by a selective depressant effect on depolarized cells (high [K]o) and cells with high frequency discharges, as is the case with lignocaine.
THE CARDIAC AND VASCULAR EFFECTS OF SODIUM GLUTAMATE
Authors: Kirkendol Paul L. , Pearson James E. , Robie Norman W.
Published: June 2007

1. The cardiovascular effects of sodium glutamate were investigated in anaesthetized dogs with bolus injections, intravenous infusions and rabbit isolated papillary muscles.

2. The intravenous bolus injections of sodium glutamate resulted in slight, transient decreases in contractile force at doses of 58 and 117 mg/kg, which were followed by brief increases in blood pressure.

3. Sodium glutamate had no effect on contractile responses of isolated papillary muscles at any of the concentrations used.

4. Infusions of glutamate produced no change in blood pressure, an increase in cardiac output, and a decrease in heart rate, total peripheral resistance and femoral vascular resistance.

5. The infusion of sodium glutamate into animals with no renal function resulted in an increased plasma osmolality and a decreased haematocrit.

6. The results from this study show that sodium glutamate had minimal cardiovascular effects. The results from the infusion data suggest that glutamate increases intravascular volume by an osmotic effect.
ORTHOSTATIC HYPOTENSION AFTER THE FIRST ADMINISTRATION OF PRAZOSIN IN HYPERTENSIVE PATIENTS: ROLE OF THE PLASMA VOLUME
Authors: Semplicini A. , Pessina A. C. , Palatini P. , Hlede M. , Dal Palù C.
Published: June 2007

1. Prazosin (2 mg, p.o.) was administered to nine patients with essential hypertension while intra‐arterial pressure was recorded by an Oxford portable apparatus. In all patients, 30 min‐3 h after the administration, systolic and diastolic pressure fell on assuming the upright posture and four patients fainted. No correlation was found between the degree of fall in pressure and the plasma concentration of the drug. Acute expansion of the plasma volume by means of 6% Dextran infusion reduced the orthostatic blood pressure fall in all cases and a significant inverse correlation was found between plasma volume and orthostatic fall of pressure.

2. After ten days of continuous treatment with prazosin, 2 mg daily, a significant decrease in blood pressure was observed while orthostatic hypotension disappeared, probably due to the plasma volume expansion induced by the drug.
ADRENALINE DEPLETION IN THE HYPOTHALAMUS OF THE RAT AFTER CHRONIC α‐METHYLDOPA
Authors: Beart P. M. , Prosser Denise , Louis W. J.
Published: June 2007

1. Individual anterior hypothalamic‐preoptic nuclei were dissected from the brains of control and α‐methyldopa treated (2 × 40 mg/kg, 5 days) rats, and the concentrations of adrenaline and other catecholamines were estimated.

2. By a combination of radioenzymatic assay and paper chromatography the concentrations of adrenaline, noradrenaline, dopamine, α‐methylnoradrenaline and α‐methyldopamine were determined concurrently in the same sample.

3. α‐Methyldopa reduced the adrenaline levels of the hypothalamic nuclei by 47–68% of control concentrations.

4. A differential displacement of the parent catecholamines was observed and the depletions were ranked: adrenaline < dopamine < noradrenaline.

5. α‐Methylnoradrenaline and α‐methyldopamine were found in all hypothalamic nuclei.

6. The depletion of hypothalamic adrenaline by α‐methyldopa could represent a pharmacological mechanism contributing to the antihypertensive action of the drug.
EFFECTS OF ISOPRENALINE, LEVODOPA AND A PHOSPHODIESTERASE INHIBITOR (ICI 63,197) ON CYCLIC AMP LEVELS AND CONTRACTIONS OF SOLEUS MUSCLES IN ANAESTHETIZED CATS
Authors: Merican Zainuddin , Nott M. W.
Published: June 2007

1. Cyclic AMP levels have been determined in the soleus muscles of anaesthetized cats in the absence of drugs, and during depression of incomplete tetanic contractions produced by (‐)‐isoprenaline, ICI 63,197 (a phosphodiesterase inhibitor) or levodopa.

2. Cyclic AMP levels were elevated at the peak of tension depression produced by isoprenaline. Effects of isoprenaline on cyclic AMP and on contractions were dose dependent and statistically significantly related one to the other. Both effects were blocked by propranolol.

3. ICI 63,197 and levodopa produced isoprenaline‐like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated.

4. The results support the involvement of cyclic AMP in the depressant effect of β‐adrenoreceptor agonists on slow‐contracting mammalian skeletal muscle.
EFFECT OF DEPLETION OF SPINAL NORADRENALINE BY 6‐HYDROXYDOPAMINE ON THE DEVELOPMENT OF RENAL HYPERTENSION IN RATS
Authors: Bosland M. C. , Versteeg D. H. G. , van Put J. , de Jong W.
Published: June 2007

1. A single injection in rats of 250 μg of 6‐hydroxydopamine HCl (6‐OHDA) into the subarachnoidal space of the spinal cord of rats resulted in a lasting, selective depletion of spinal noradrenaline. Dopamine levels in the spinal cord and catecholamine levels in various brain regions were not markedly affected.

2. When ether anaesthesia was used spinal noradrenaline was found to be almost completely depleted by the administration of 6‐OHDA. Only partial depletion was achieved when pentobarbitone anaesthesia or neuroleptic analgesia was used.

3. The blood pressure rise caused by electrical stimulation of the posterior hypothalamus was not affected by 6‐OHDA treatment 7 days previously.

4. 6‐OHDA administration did not influence the development of two‐kidney Goldblatt hypertension. When 6‐OHDA was administered 7 days before clipping, a slight delay of the development was observed, but this did not occur when 6‐OHDA treatment was given 3–4 h before clipping.

5. It is concluded that intact spinal noradrenergic neurotransmission is neither a prerequisite for the development of two‐kidney Goldblatt hypertension, nor for the pressor response to hypothalamic stimulation.
STUDIES IN THE RAT ON ENDRALAZINE, A NEW ANTIHYPERTENSIVE DRUG STRUCTURALLY RELATED TO HYDRALAZINE
Authors: Oates Helen F. , Stoker Lynette M.
Published: June 2007

1. The effects on blood pressure, heart rate and plasma renin activity of a new hydralazine congener, endralazine, were evaluated in anaesthetized rats. Dose‐response relationships for endralazine, hydralazine and diazoxide, administered intravenously, were compared, and the interactions of endralazine with the ganglionic blocking agent, pentolinium, or with adrenaline, noradrenaline and angiotensin II were examined.

2. In the dose range 0.05 to 1.0 mg/kg, endralazine produced prompt dose‐related reductions in systolic and diastolic blood pressure, with relatively little effect on heart rate. The drug had a pronounced dose‐related renin stimulating effect.

3. Endralazine retained approximately 80% of its hypotensive activity after pretreatment with pentolinium, and caused no significant attenuation of pressor responses to adrenaline, noradrenaline or angiotensin II.

4. Endralazine was an effective hypotensive agent, with a prompt onset of action, a prolonged and stable effect, and a potency at least twice that of hydralazine and 20 to 25 times that of diazoxide. The data are consistent with a predominantly direct vasodilator mode of action.
THE EFFECTS OF GABA‐ERGIC DRUGS ON ENKEPHALIN‐INDUCED MOTOR SEIZURE PHENOMENA IN THE RAT
Authors: Dzoljic M. R. , Poel‐Heisterkamp A. L. v. d.
Published: June 2007

1. The relationship between the effects of GABA‐ergic drugs and D‐ala2 ‐met‐enkephalinamide (DALA)‐induced myoclonic contractions of inframandibular muscles has been studied in the rat.

2. GABA‐ergic drugs altered enkephalin‐induced myoclonic contractions in the following manner:

(a) The GABA‐mimetic drugs, muscimol, gabaculine and baclofen, decreased DALA‐induced myoclonic contractions.

(b)The GABA antagonist, bicuculline and the anticonvulsant substance, sodium valproate (dipropylacetic acid, DPA) potentiated DALA‐induced myoclonic contractions. The potentiating effect of DPA is probably due to its opiate‐like activity, since naloxone abolished this effect.

3. The modulatory effect of the GABA‐mimetic drug on enkephalin‐induced myoclonic contractions may give grounds for further study to test the possible use of other GABA‐mimetic drugs and possibly opiate antagonists for the treatment of myoclonic syndromes.
CARDIAC β‐ADRENORECEPTORS IN THE THYROXINE‐TREATED DOG
Authors: Ho K. , Lloyd B. L. , Taylor R. R.
Published: June 2007

1. Myocardial β‐adrenoreceptors, assessed in membrane preparations of left ventricle by 3 H‐dihydroalprenolol binding, were compared in dogs following thyroxine administration (n= 6), aortocaval fistula (n= 12), and in normal dogs (n= 7).

2. Left ventricular hypertrophy occurred in response to both aortocaval fistula and thyroxine treatment. Yield of myocardial membrane between the different groups was not significantly different.

3. Binding site concentration (pmol/mg membrane protein) in dogs with aortocaval fistulae was similar to that in normal dogs and was not significantly influenced by the presence or absence of cardiac failure, degree of hypertrophy or duration of fistula.

4. Thyroxine‐treated dogs had an increased concentration of binding sites (c. 1.8‐fold) compared with both fistula and normal groups, while binding affinities were similar in all groups.

5. The data suggest that β‐adrenoreceptor concentrations in myocardium increase as a direct result of thyroid hormone action rather than as a result of secondary haemodynamic changes or ventricular hypertrophy.
IMPORTANCE OF CIRCULATING ANGIOTENSIN II FOR ELEVATION OF ARTERIAL PRESSURE DURING ACUTE HYPERCAPNIA IN ANAESTHETIZED DOGS
Authors: Staszewska‐Barczak Janina , Dusting Gregory J.
Published: June 2007

1. In anaesthetized dogs acute hypercapnia produced by ventilation with 10% CO2 in air caused release of vasoactive substances and changes of arterial pressure. Catecholamines, angiotensin II, bradykinin and prostaglandin‐like substances were bioassayed continuously in arterial blood using the blood‐bathed organ technique of Vane.

2. Acute hypercapnia in control dogs causes responses of rat stomach strip, chick rectum and rat colon indicating initial release of noradrenaline, followed by angiotensin II, and occasionally release of prostaglandin‐like substances into the circulation.

3. The initial transient, pressor response to hypercapnia coincided with the appearance of noradrenaline, and the secondary progressive rise in arterial pressure was accompanied by increased circulating angiotensin II.

4. In dogs treated with the angiotensin converting enzyme inhibitor SQ 20881 (1–2 mg/kg, i.v.), hypercapnia did not cause the secondary elevation of arterial pressure despite pronounced elevation of noradrenaline levels in the circulation. Increased arterial concentrations of bradykinin of less than 1 ng/ml, assayed by a strip of cat jejunum, were detected during hypercapnia in four out of six dogs treated with SQ 20881, but not in untreated dogs.

5. Intravenous infusion of the angiotensin antagonist [Sar1‐Ile8]‐angiotensin II (0.5–1.0 μg/kg per min) attenuated the secondary pressor response to hypercapnia and abolished the contractions of rat colon produced by hypercapnia and angiotensin II.

6. The results indicate that adrenergic stimulation may be responsible for the transient pressor response on induction of hypercapnia, but elevation of angiotensin II activity in the circulation is of major importance for mediating the secondary progressive rise in arterial pressure during the later stage of acute respiratory acidosis.

7. After inhibition of angiotensin converting enzyme, hypercapnia reduces arterial pressure, not only because the vasoconstrictor effect of angiotensin has been removed, but also because inhibition of pulmonary kininase may allow vasodilator kinins to reach the arterial circulation.
SODIUM‐DEPENDENT RELAXATION IN ARTERIAL SMOOTH MUSCLE *
Authors: Gillespie Mark N. , Niehaus Karl E. , Rodger Ian W. , Diamond Louis
Published: June 2007

1. The effects of isosmotic substitution of choline for sodium on resting tension and on relaxation after noradrenaline‐induced contraction was studied in rabbit isolated aortic strips immersed in Hepes‐buffered physiologic salt solution (PSS) warmed to 37°C and gassed with 100% O2.

2. Isosmotic substitution of choline for sodium produced a sustained increase in resting tension which effectively prevented any evaluation of the influence of sodium on relaxation. The increase in resting tension was insensitive to 10−8 mol/1 atropine but was abolished by 10 min exposure to calcium‐free PSS prior to replacement of sodium.

3. Under sodium‐calcium free conditions which eliminated the increase in resting tension observed in sodium‐free PSS, stimulation with 10−5 mol/1 noradrenaline initiated contractions that were 55 ± 7.5% of the control response in normal PSS. Washout of noradrenaline with sodium‐calcium‐free PSS failed to produce any decrement in tension. However, restoration of the normal sodium resulted in gradual relaxation.

4. These results suggest that sodium is required for relaxation after noradrenaline‐induced contraction of arterial smooth muscle.
SYSTEMIC AND REGIONAL HAEMODYNAMIC RESPONSES TO ISOPRENALINE IN CONSCIOUS RENAL HYPERTENSIVE RABBITS
Authors: van Boom Martin , Saxena Pramod R.
Published: June 2007

1. Using the electromagnetic flow probe and the radioactive microsphere technique, systemic and regional haemodynamic variables were measured in conscious normotensive and hypertensive rabbits. The rabbits were made hypertensive by unilateral nephrectomy combined with cellophane‐wrapping of the remaining kidney and systemic and regional haemodynamic effects of isoprenaline infusions (0.5 μg‐kg−1 .min−1) were compared in the two groups of animals.

2. Isoprenaline evoked increases in heart rate and cardiac index while the total peripheral resistance decreased. In the hypertensive rabbits the effects were similar, except for a significantly more pronounced decrease in blood pressure.

3. Isoprenaline increased the fraction of the cardiac output delivered to the heart, skin and fat, at the expense of the fractions to the brain, stomach, small intestine, pancreas, liver and kidney(s) in both normotensive and hypertensive animals. Local peripheral resistance was decreased, most prominently, in the heart, skin, skeletal muscle and fat.

4. In the normotensive rabbits pretreatment with propranolol (4 mg.kg−1 infused in 1 h) effectively blocked the cardiovascular responses following isoprenaline infusion.

5. Since the systemic and regional haemodynamic effects of isoprenaline were not less (if anything, slightly more) in the hypertensive than in the normotensive rabbits, our results provide no evidence for subsensitivity of β‐adrenoceptors as a contributory factor in the development of hypertension in this model.
THE β‐ADRENORECEPTOR IN HUMAN LYMPHOCYTES
Authors: Watanabe Yasuhiro , Lai Rong‐Tsan , Yoshida Hiroshi
Published: June 2007

The β‐adrenoreceptors of human lymphocytes were investigated by binding assays using a radiolabeled β‐adrenoreceptor agonist, 3H‐hydroxybenzylisoproterenol, in an intact cell system. Intact human lymphocytes had binding sites for the ligand, which seemed to represent physiological β‐adrenoreceptors. Thus, assay of binding of the β‐adrenergic agonist, 3H‐HBI, by intact lymphocytes can be used to study β‐adrenoreceptors in human tissue and to elucidate possible β‐adrenoreceptor disorders in human diseases.
DIRECT VASODILATOR ACTIVITY OF ATROPINE IN THE RAT PERFUSED HINDLIMB PREPARATION
Authors: Merrick B. Alex , Holcslaw Terry L.
Published: June 2007

1. The autoperfused hindlimb technique in the rat was used to determine the effects of atropine upon the peripheral vasculature.

2. Injection of atropine (0.1–0.8 μmoles) into the hindlimb perfusion circuit resulted in a dose‐dependent decrease in perfusion pressure which was immediate in onset and always preceded systemic pressure changes. The duration of vasodilation lengthened with increasing doses of atropine and ranged from 1.5 to 9 min.

3. During atropine‐induced vasodilation, challenging doses of acetylcholine did not alter the perfusion pressure.

4. These experiments suggest that atropine is capable of direct vasodilator activity upon the peripheral vasculature in which a muscarinic mechanism appears unlikely.
THE INFLUENCE OF HEART RATE ON DIGOXIN‐INDUCED INHIBITION OF MYOCARDIAL NA+‐K+‐ATPASE ACTIVITY IN THE DOG
Authors: Marsh A. J. , Lloyd B. L. , Taylor R. R.
Published: June 2007

1. Groups of sedated dogs were studied at spontaneous heart rates (HR), 55–100/min, or at paced HR 200/min, with or without intravenous digoxin administration. After 60 min, active rubidium uptake (86Rb+) of ventricular samples was determined in vitro.

2. Untreated fast and slow HR groups had similar uptakes. Following digoxin, 0.08 mg/kg, uptake was less at fast than slow HR (63.8, s.e.m. = 4.5 v. 87.5, s.e.m. = 5.0 pmol/mg LV/15 min, P< 0.01). After 0.125 mg/kg, values were again lower in the fast HR group in which five of seven developed ventricular tachycardia.

3. Heart rate does not alter in vitro activity of myocardial Na+‐K+‐ATPase but does influence inhibition of the enzyme resulting from digoxin administration.