bluuebunny/crossref_metadata_2025 huggingface dataset:
SYNTHESIS OF MOUSE RENIN AS A 2‐5‐33‐5 KILODALTON PRE‐PRO‐ TWO‐CHAIN MOLECULE AND USE OF ITS cDNA TO IDENTIFY THE HUMAN GENE
Authors: Morris Brian J. , Catanzaro Daniel F. , Mullins John J. , Hardman Judy , Shine John
Published: June 2007

1. A DNA coding for mouse submandibular gland (MSG) renin was used in studies of the biosynthesis and processing of MSG renin and precursors and as a probe for identification of the human renin gene.

2. A 2 kilodalton signal peptide was demonstrated by cleavage of preprorenin (45 kilodaltons) in the presence of microsomal membranes from dog pancreas. Prior selection of renin mRNA by hybridization with its cDNA obviated the possibility that a protease translated from total MSG mRNA could be activated by the microsomal membranes and then act on the primary translation product.

3. In vitro labelling experiments with female MSG demonstrated that prorenin (43 kilodaltons) is rapidly converted to renin (38 kilodaltons) and that testosterone stimulated synthesis by increasing transcription of renin mRNA.

4. Electrophoresis under non‐reducing conditions demonstrated 38 kilodalton renin which when reduced ran as two bands of 33 and 5 kilodaltons. Thus, native MSG renin has two chains linked by disulphide bonding. Hydrolysis of the 38 kilodalton single chain occurred only slowly during in vitro labelling.

5. Prorenin bound only weakly to a pepstatin affinity column and could be activated by adding trypsin to column fractions. Both 38 kilodalton single and two chain renin bound strongly however, suggesting that both are active.

6. Base sequencing of MSG renin cDNA indicated an Arg‐Arg residue additional to the published amino acid sequence of the heavy chain. This may account for the two forms seen on isolectric focusing.

7. Mouse renin cDNA was used as a hybridization probe in screening a human genomic library in order to identify the human renin gene. The DNA in positive colonies had overlapping restriction maps and the coding region was found.
DEMONSTRATION OF SPECIFIC RECEPTORS FOR ADENOSINE IN GUINEA‐PIG MYOCARDIUM
Authors: Leung E. , Johnston C. I. , Woodcock E. A.
Published: June 2007

1 Adenosine analogues N6‐phenylisopropyladenosine and 5′‐N‐ethylcarbox‐amidoadenosine inhibit cardiac adenylate cyclase in a concentration dependent manner.

2 Inhibition of adenylate cyclase required the presence of guanosine‐triphosphate and Mg2+ ion. The concentration of Na+ ion was critically important: maximal inhibition was observed at 50 mmol/1 Na+.

3 8‐Phenyltheophylline and isobutylmethylxanthine antagonized the inhibition of adenylate cyclase mediated by adenosine analogues.

4. Adenosine receptors of the inhibitory type (R1 or A1) are present in guinea‐pig myocardium and may mediate some actions of adenosine.
DIFFERENTIAL BLOOD PRESSURE AND METABOLIC EFFECTS OF 9α‐FLUOROCORTISOL IN MAN
Authors: Whitworth Judith A. , Saines Dianne , Thatcher Robin
Published: June 2007

1. The blood pressure and metabolic effects of 9α‐fluorocortisol at 0.15 mg/day and 1.5 mg/day were examined in man.

2. At high dose, systolic pressure and body weight rose, and plasma [K+], urinary sodium excretion and renin concentration fell. At low dose similar metabolic effects were seen but blood pressure was unchanged.

3. 9α‐Fluorocortisol has ‘mineralocorticoid’ effects in man at a dose which does not alter blood pressure. These studies do not provide evidence of a ‘hyperten‐sinogenic’ class of steroid hormone action in man.
VERAPAMIL‐INDUCED CONTRACTURE IN AN EXCISED, BLOOD‐PERFUSED SKELETAL MUSCLE PREPARATION FROM THE DOG
Authors: Sato T. , Suzuki K. , Aoyama T. , Ono H.
Published: June 2007

1. The ability of verapamil to induce a contractile response in skeletal muscle was investigated using the canine isolated, blood‐perfused diaphragm preparation.

2. Verapamil‐induced contracture was characterized by a biphasic increase in muscle tension consisting of an initial phasic and subsequent tonic contracture.

3. The second tonic component of the verapamil‐induced contracture was inhibited by procaine, but procaine had no effect on the initial phasic contracture.

4. Verapamil potentiated both KCl‐ and caffeine‐induced contractures during the second tonic stage. This action might be explained by enhancement by the drug of availability, or by an increased sensitivity of the contractile machinery to calcium liberated by membrane depolarization or by the calcium‐induced calcium release mechanism.

5. The second tonic component of verapamil‐induced contracture was much less than the initial phasic component. It seems, therefore, that the calcium release induced by the procaine‐resistant process is the principal action of verapamil in inducing contracture in skeletal muscle.
CEREBRAL MECHANISMS INFLUENCING RENAL SODIUM EXCRETION IN DEHYDRATED SHEEP
Authors: McKinley M. J. , Denton D. A. , Fryday H. W. , Weisinger R. S.
Published: June 2007

1. Reducing the cerebrospinal fluid concentration of NaCl by infusion into a lateral cerebral ventricle of isotonic solutions of 0.3 mol/1 mannitol or sucrose at 1 ml/h for 2 h caused a large reduction in renal Na excretion in conscious sheep deprived of water for 24 or 48 h.

2. Infusion of 0.3 mol/1 mannitol into the lateral ventricle of water‐replete sheep did not alter renal Na excretion but induced a water diuresis.

3. These data indicate that during dehydration, renal Na excretion may be under the control of the brain. The pathway(s) from brain to kidney mediating this antinatriuretic effect are not known.
INHIBITION OF AMINO ACID TRANSMITTER RELEASE FROM RAT BRAIN SLICES BY PHENYTOIN AND RELATED ANTICONVULSANTS
Authors: Skerritt John H. , Johnston Graham A. R.
Published: June 2007

1. The in vitro effects of the major non‐benzodiazepine anticonvulsants were studied upon potassium‐stimulated release of radiolabelled GABA and D‐aspartate from minislices of rat cerebral cortex.

2. At 100 μmol/1, some anticonvulsants effective in grand mal seizures (phenytoin, phenobarbitone, mephobarbitone and beclamide) selectively inhibited K+‐evoked release of the excitant amino acid D‐aspartate, consistent with an anticonvulsant action.

3. In contrast, several other anticonvulsants, namely ethosuximide, methsuximide, carbamazepine, sulthiame and dipropylacetate failed to alter potassium‐evoked release of either amino acid.

4. The ionic basis of phenytoin action on release was further studied; interactions with both neuronal calcium and sodium ion channels appear necessary for the drug's inhibitory action.
DUAL MODES OF ACTION FOR DISODIUM CROMOGLYCATE IN INHIBITION OF ANTIGEN‐INDUCED CONTRACTIONS OF GUINEA‐PIG ISOLATED AIRWAYS SMOOTH MUSCLE
Authors: Stewart A. G. , Fennessy M. R.
Published: June 2007

1. Disodium cromoglycate (DSCG; 10 μmol/l‐1 mmol/l) relaxed the tone induced in the guinea‐pig isolated trachea by histamine (5 μmol/l). Both isoprenaline and fenoterol were approximately 1000 times more potent than DSCG in relaxing tracheal smooth muscle.

2. Ovalbumin (1 μg/ml) contracted isolated tracheal and parenchymal strips from sensitized guinea‐pigs. The sensitization procedure used was selective for eliciting IgG antibody production.

3. In concentrations equieffective for relaxation of the isolated trachea, fenoterol (20 nmol/l), isoprenaline (60 nmol/l) and DSCG (100 μmol/l) inhibited ovalbumin‐induced contractions of both tracheal and parenchymal strip preparations.

4. DSCG produced a significantly greater (P < 0.05) inhibition of ovalbumin‐induced contractions of isolated trachea than did isoprenaline, suggesting that at 100 μmol/l DSCG produced a greater inhibition of mediator release than that produced by isoprenaline.

5. Compound 48/80 (200 μg/ml) contracted the isolated trachea whereas this concentration had no contractile effect on the parenchymal strip. The failure of DSCG to inhibit compound 48/80 induced contractions of the isolated trachea together with the lack of contractile effect of compound 48/80 on the parenchymal strip suggest that compound 48/80 is inferior to antigenic stimulation as a reliable analogue of immunological activation of mast cells and consequent mediator release.

6. On the basis of DSCG‐induced relaxation of the isolated trachea and greater inhibition of ovalbumin‐induced contractions relative to that produced by isoprenaline, it is concluded that DSCG has dual modes of action in inhibition of antigen‐induced contraction of isolated airways smooth muscle, that is, DSCG produced functional antagonism of antigen‐induced mediators in addition to inhibiting mediator release.
A STUDY OF STIMULATION‐EVOKED ACTIVATION OF α2‐ADRENOCEPTORS IN THE RAT ISOLATED VAS DEFERENS
Authors: Pennefather Jocelyn N.
Published: June 2007

1. Experiments were performed with prostatic and epididymal segments of rat vas deferens to determine whether α2‐adrenoceptors in this organ were activated during field stimulation of sympathetic terminals with short trains of pulses applied at low frequencies.

2. In prostatic segments the magnitude of twitches evoked by trains of ten field pulses at 1 or 2 Hz declined after 2–3 s of stimulation. In contrast, facilitation of twitches and fusion of contractions occurred when similar stimulation was applied to epididymal segments.

3. In prostatic segments from rats treated with reserpine (2.5 mg/kg i.p.) 24 h previously, there was no decline in the magnitude of twitches produced by successive impulses in a train of stimulating pulses. In epididymal segments from reserpine‐treated rats facilitation of twitches in response to successive impulses in each train still occurred.

4. In prostatic segments cocaine (5 and 10 μmol/1) enhanced twitch fade with stimulation at 1 and 2 Hz without altering the time for onset of this effect. In epididymal segments cocaine led to enhancement and prolongation of contractile responses.

5. In prostatic segments yohimbine (0.01–0.06 μmol/l) reduced or reversed the effect of cocaine in enhancing twitch fade. In preparations where the reversal of the effect of cocaine by yohimbine was incomplete, subsequent addition of phentolamine (1 μmol/l) produced complete reversal.

6. In epididymal segments yohimbine (0.01 μmol/l) produced a further enhancement in the twitch responses to stimulation at 1 and 2 Hz. Subsequent addition of phentolamine (1 μmol/l) reversed the facilitatory effects of cocaine and yohimbine.

7. Propranolol (10 μmol/l) was without effect upon responses to stimulation in either segment of rat vasa deferentia.

8. These experiments indicate that noradrenaline, released by short trains of impulses applied at low frequency to hypogastric nerve terminals activates prejuctional α2‐adrenoceptors in the prostatic segment of the vas deferens. In the epididymal portion the effects arising from activation of prejunctional α2‐adrenoceptors are outweighed by the consequences of activation of extrajunctional α1‐adrenoceptors located on longitudinally arranged muscle.
SECRETORY AND VASCULAR EFFECTS OF THE OPTICAL ISOMERS OF NICARDIPINE
Authors: Iwatsuki K. , Iijima F. , Chiba S.
Published: June 2007

1. The effects of optical isomers of nicardipine on the secretion of pancreatic juice and blood flow were investigated in the dog‐isolated, blood‐perfused pancreas.

2. Intra‐arterial administration of (‐)‐nicardipine (10–300 μg) caused a dosedependent increase in pancreatic secretion. However, the (+)‐isomer was much less potent than the (‐)‐isomer and even in 300 μg of (+)‐isomer caused only a slight secretion.

3. (+)‐ And (‐)‐nicardipine increased perfusion blood flow in a dose‐dependent manner, and (+)‐nicardipine was approximately five times as potent as the (‐)‐isomers. The maximum increase in a flow rate was produced by 30 μg of (+)‐isomer and 100 μg of (‐)‐isomer.

4. Bicarbonate concentration in pancreatic juice induced by (‐)‐ and (+)‐nicardipine was increased in a dose‐dependent manner, but the protein concentration was only increased slightly.

5. From these results, it is concluded that there is a stereoselectivity in the secretory and vascular actions of optical isomers of nicardipine.
EFFECTS OF Δ1 AND Δ6‐TETRAHYDROCANNABINOL ON THE ADENYLATE CYCLASE ACTIVITY IN VENTRICULAR TISSUE OF THE RAT HEART
Authors: Li D. M. F. , Ng Camay K. M.
Published: June 2007

1. Adrenaline 1 μg markedly elevated the activity of adenylate cyclase in ventricular tissue of rat hearts.

2. Δ1‐THC 25, 50 and 100 μg significantly reduced the adenylate cyclase activity with the maximum effect observed with the dose or 25 μg. Doses below or above this range did not produce any significant effect on the enzyme activity.

3. Neither Δ6‐THC 25 and 100 μg nor PVP 400 μg had any significant action on adenylate cyclase.

4. The Δ1‐THC‐induced lowering of the cyclic AMP concentration in ventricular tissue of rat hearts can be explained, at least partly, by its ability to reduce the activity of adenylate cyclase in these tissues. It is suggested that this enzyme inhibition underlies the cardiac depressant action of Δ1‐THC.
CARDIAC HYPERTROPHY IN THE ABSENCE OF PRESSURE OVERLOAD: AN EXPERIMENTAL AND CLINICAL REPORT
Authors: Genovese Arturo , Latte Salvatore , Betocchi Sandro , Bozzaotre Mariano , Giunta Anna , Chiariello Massimo
Published: June 2007

1. A simulated altitude of 7000 m was applied in rats chronically exposed to hypoxia in a hypobaric chamber. In these experimental conditions the contralateral ventricle not exposed to pressure overload (that is, the left) showed a significant degree of hypertrophy. The hypoxic stimulus did not affect systemic artery pressure or the heart rate.

2. Chronic adrenergic stimulation performed in the rat treated with low doses of isoprenaline (a direct stimulating adrenergic drug) or with tyramine (primarily a releaser of endogenous catecholamines) induced hypertrophy of the right ventricle, left ventricle, and interventricular septum without modifying the haemodynamic parameters mentioned above.

3. The development of ventricular hypertrophy in the absence of pressure overload is stressed.

4. A role for neurohumoral factors (that is, adrenergic stimulation and catecholamines) in the development of ventricular hypertrophy is suggested.
STUDIES ON THE MECHANISM OF ACTION OF THE HYPOTENSIVE EFFECT OF KETANSERIN
Authors: Marwood John F. , Stokes Gordon S.
Published: June 2007

1. Ketanserin, 0.01–3.0 mg/kg i.v., was found to cause a dose‐related fall in blood pressure in anaesthetized rats. However, these decreases were only significant after 1 and 3 mg/kg doses. Subsequent administration of prazosin, 0.2 mg/kg i.v., had no significant effect on blood pressure.

2. In the presence of ketanserin 3 mg/kg, plus prazosin 0.2 mg/kg, adenosine caused a significant dose‐dependent fall in blood pressure in anaesthetized rats.

3. Methysergide, 1 mg/kg i.v., significantly attenuated the blood pressure responses to serotonin in anaesthetized rats whereas ketanserin (1 and 3 mg/kg) had no overall effect on serotonin responses.

4. Ketanserin, 1 and 3 mg/kg i.v., was found to antagonize the pressor effects of phenylephrine and reverse the pressor effects of adrenaline in anaesthetized rats. Responses to angiotensin II were not significantly affected by ketanserin.

5. These results suggest that ketanserin lowers blood pressure in anaesthetized rats by blockade of α‐adrenoceptors.
EFFERENT MECHANISMS RESPONSIBLE FOR THE BRADYCARDIA PRODUCED BY LESIONS COINCIDING WITH THE A1 GROUP OF CENTRAL CATECHOLAMINE NEURONS IN THE CONSCIOUS RABBIT
Authors: Denoroy Luc , West Malcolm J. , Chalmers John
Published: June 2007

1. The effector mechanisms responsible for the bradycardia evoked by bilateral lesions of the brainstem coinciding with the A1 catecholamine cells were analyzed in four groups of rabbits. Sham or lesion operations were carried out in animals with intact cardiac effectors, with cardiac sympathetic block induced by propranolol, with cardiac vagal block induced by methylscopolamine and with total cardiac autonomic block induced by the use of both drugs together.

2. Lesions produced a transient increase in blood pressure of 25 (s.e.m. =4) mmHg and a transient bradycardia, or increase in heart period of 141 (s.e.m. =18) ms. The bradycardia had both baroreflex‐independent and baroreflex‐dependent components as determined from analysis of stimulus response curves relating heart period to mean arterial pressure.

3. The ‘baroindependent’ component of the bradycardia, measured as a lengthening in heart period, ranged from 35–49 ms in the four groups of animals and was unaffected by administration of propranolol alone, methylscopolamine alone, or of both together. These findings suggest that the baroindependent slowing of the heart is not mediated through changes in activity of either the cardiac sympathetic nerves or of the vagal fibres innervating the heart.

4. The ‘baroreceptor’ component of the bradycardia reflects that portion of the decrease in heart rate resulting directly from the increase in blood pressure. This component was found to account for a lengthening in the heart period of 81 (s.e.m. =23) ms in animals with intact effector mechanisms: it was virtually abolished by methylscopolamine (0 ms, s.e.m. =13) but not significantly affected by propranolol (54 ms, s.e.m. =25), indicating that this barodependent component is predominantly mediated through the vagus.
HAEMODYNAMIC AND HORMONAL EFFECTS OF PRAZOSIN ON HEAD‐UP TILT IN ESSENTIAL HYPERTENSIVE PATIENTS: COMPARISON WITH THOSE OF PROPRANOLOL
Authors: Kida Osamu , Morotomi Yasuyuki , Higa Toshinobu , Kodama Kenji , Someya Noriyuki , Tanaka Kenjiro
Published: June 2007

1. To evaluate the haemodynamic and hormonal effects of prazosin, head‐up tilt was performed in 10 essential hypertensive patients, and these effects of prazosin on the tilt were compared with those of propranolol. The tilts were performed in control phase and the last days of treatment for two weeks with propranolol (90 mg/day) or prazosin (3–6 mg/day).

2. Each drug significantly lowered the mean blood pressure at rest, and also suppressed its rise on the tilt. Heart rates were significantly increased by the tilt in the control phase, in the propranolol phase and in the prazosin phase. Cardiac index was significantly reduced by the tilt from 2.66 (s.e.m. =0.22) 1/min per m2 to 2.08 (s.e.m. =0.20) in the propranolol phase. However, there were not significant changes in other phases. Total peripheral resistance indices were significantly increased by the tilt in all three phases. Plasma renin activity and plasma aldosterone were significantly increased by the tilt from 2.14 (s.e.m. =0.47) ng/ml per h to 2.46 (s.e.m. =0.54) and from 50.6 (s.e.m. =12.9) pg/ml to 74.9 (s.e.m. =14.9) respectively, in the control phase. And they were also significantly increased from 1.06 (s.e.m. =0.29) to 1.65 (s.e.m. =0.45) and from 41.4 (s.e.m. =16.3) to 54.0 (s.e.m. =17.4) in the prazosin phase. There were no significant increases during the administration of propranolol.

3. We observed that prazosin did not alter heart rate and cardiac index, but suppressed the renin‐angiotensin system at rest. It is suggested that prazosin did not influence haemodynamic and hormonal responses to the tilt.
ACUTE EFFECTS OF COLD ON BLOOD PRESSURE, RENIN‐ANGIOTENSINALDOSTERONE SYSTEM, CATECHOLAMINES AND ADRENAL STEROIDS IN MAN
Authors: Hiramatsu Kunihide , Yamada Takashi , Katakura Masafumi
Published: June 2007

1. In an attempt to study effects of cold on blood pressure and the reninangiotensin‐aldosterone system, 34 healthy young subjects with or without a family history of essential hypertension were exposed to moderate cold (4°C for 1 h) or severe cold (immersion of the hands to 0°C for 10 min). Moderate cold elevated blood pressure, aldosterone, cortisol and noradrenaline when the subjects wore summer clothing but not when the subjects wore winter clothing. Regardless of the clothing worn, skin blood flow and plasma renin activity decreased significantly in response to moderate cold but angiotensin II decreased insignificantly.

2. Severe cold elevated blood pressure, cortisol, aldosterone and noradrenaline. Administration of dexamethasone significantly depressed an increase of aldosterone and cortisol in response to cold but failed to effect an elevation of blood pressure and noradrenaline. Plasma renin activity and angiotensin II concentration were not affected at all during and after cold exposure.

3. It is suggested that, among the various hormones studied, noradrenaline is the only hormone responsible for an elevation of blood pressure in response to cold.
AN IMPORTANT EFFECT OF TSH ON PROSTACYCLIN CONCENTRATION IN PORCINE THYROID CELLS
Authors: Takasu N. , Takahashi K. , Ishigami T. , Shimizu Y. , Yamada T. , Sato S.
Published: June 2007

1. Fresh thyroid slices obtained from normal pigs contained prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) and prostacyclin (PGI2, measured as the end metabolite, 6‐keto PGF1α), but the concentrations of PGI2 exceeded those of PGE2 and PGF2α. A preferential increase of PGI2 was produced when the slices were exposed to a large dose of TSH (thyroid‐stimulating hormone).

2. When thyroid cells were isolated and cultured in the absence of TSH, thyroidal concentrations of PGI2, PGE2 and PGF2α were about equal. When the cells were acutely exposed to a large dose of TSH, intrathyroidal concentration of prostaglandin increased significantly, but the relative concentrations of prostaglandins were not markedly altered.

3. When thyroid cells were cultured in the presence of a small dose of TSH, relative concentrations of thyroidal prostaglandins were comparable to those of fresh thyroid slices, as a result of a preferential increase of PGI2 and decreases of PGE2 and PGF2α. Further increase of PGI2 was induced when the cells cultured with TSH were acutely exposed to a large dose of TSH.

4. It is concluded that although cells contain PGE2, PGF2α and PGI2, a preferential accumulation of PGI2 is found only when thyroid cells are chronically stimulated by TSH.
ACTIVITIES OF NAD+‐DEPENDENT ALDEHYDE DEHYDROGENASE AND ALCOHOL DEHYDROGENASE IN THE LIVER OF SPONTANEOUSLY HYPERTENSIVE RATS IN THE PROCESS OF DEVELOPMENT
Authors: Shiohara E. , Tsukada M. , Iwatsuki K. , Iijima F. , Chiba S.
Published: June 2007

1. The difference in the basal activities of NAD+‐dependent aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) was investigated in the liver of age‐matched spontaneously hypertensive (SH) and normotensive Wistar Kyoto (WK) rats.

2. A significant difference between the SH and WK rats in the basal ALDH activity, ADH activity and the protein content of subcellular fractions was observed. The activities of mitochondrial low Km‐ and high Km‐ALDH in the SH rats at 5–8 weeks of age were higher than those in the WK rats. The microsomal high Km‐ALDH activity in the SH rats at 5 and 11 weeks of age was higher than that in the WK rats. The ADH activities in the SH rats at 5–14 weeks of age were lower than those in the WK rats. The mitochondrial protein content in the SH rats at 5–14 weeks of age was higher than those in the WK rats.

3. At 14 weeks of age, an increase in the blood acetaldehyde level was observed after an intraperitoneal injection of 1.5 g/kg of ethanol in the SH rats. No difference in blood ethanol level was observed between the SH and WK rats.
EFFECTS OF BROMOCRIPTINE ON PANCREATIC SECRETION IN THE ISOLATED, BLOOD‐PERFUSED PANCREAS OF THE DOG
Authors: Iwatsuki K. , Iijima F. , Chiba S.
Published: June 2007

1. Effects of bromocriptine on the secretion of pancreatic juice were investigated with dog isolated, blood‐perfused pancreas.

2. Bromocriptine (1–10 mg) caused dose‐dependent increases in the secretion of pancreatic juice. However, bromocriptine did not affect the perfusion blood flow rate. The secretory response to bromocriptine was inhibited by pretreatment with a dopamine antagonist, sulpiride, but not by phentolamine, propranolol, atropine, metiamide, indomethacin or tetrodotoxin.

3. Bromocriptine caused a dopamine‐like secretion of the pancreatic juice containing a high concentration of bicarbonate but had little effect on protein output.

4. These results suggest that bromocriptine increases pancreatic secretion stimulating directly on pancreatic dopamine receptors.
COMPARISON OF THE REFLEX EFFECTS OF ARTERIAL BARORECEPTORS AND CARDIAC RECEPTORS ON THE HEART RATE OF CONSCIOUS RABBITS
Authors: Ludbrook John
Published: June 2007

1. The reflex effects on heart rate (HR) of presumptive cardiac receptors have been differentiated from those of the arterial baroreceptors in conscious rabbits by inflating cuffs on the ascending aorta, descending aorta, inferior vena cava and pulmonary artery.

2. When the outflow from the right ventricle was progressively impeded the accompanying increase in HR was entirely explicable by unloading of the arterial baroreceptors.

3. As the outflow from the left ventricle was progressively impeded there was an initial increase in HR due to unloading of the arterial baroreceptors, followed by a progressive decline. This decline was attributed to a reflex arising from vagallyinnervated receptors in the left side of the heart. The threshold of this cardiac receptor‐HR reflex occurred at a higher level of mean aortic pressure than that at which the effects of the arterial baroreceptors on HR were maximal. Cholinergic (vagal) efferent nerves were responsible for two‐thirds of the decline in HR caused by the reflex.

4. The properties of the cardiac receptor‐HR reflex were altered by drugs that affect myocardial contractility. Isoprenaline raised the mean aortic pressure at which the threshold occurred, but lowered the corresponding level of left ventricular end‐diastolic pressure. Propranolol virtually abolished the reflex, even though left ventricular end‐diastolic pressure reached a high level.

5. It is concluded that in the conscious rabbit the arterial baroreceptor reflexes normally prevent the threshold of the cardiac receptor‐HR reflex from being attained.
COMPARISON OF THE EFFECTS OF d‐AMPHETAMINE ON FI AND DRL SCHEDULE PERFORMANCE OF SELF‐STIMULATING RATS
Authors: Nalwa V. , Rao P. S.
Published: June 2007

1. Six rats bar‐pressed for intracranial self‐stimulation in a Skinner box on fixed interval and differential reinforcement of low rate schedules with an interval parameter of 1.3 s.

2. After amphetamine timing efficiency was reduced immediately on both the schedules; it recovered after 60 min on the DRL schedule but not within 120 min on the FI schedule. Response rates increased on both the schedules.

3. The increased response rates correlated with the low efficiency on the DRL but not on the FI schedule.

4. The selective sparing of DRL performance is in line with the similarity between the effects of amphetamine and frontal cortical lesions.
EFFECT OF MEFENAMIC ACID ON PLASMA PROTEIN‐THYROID HORMONE INTERACTION, MONODEIODINATION OF THYROXINE, URINARY EXCRETION OF TRI‐IODOTHYRONINE AND THYROTROPIN REGULATION
Authors: Koizumi Y. , Sato A. , Yamada T. , Inada M.
Published: June 2007

1. A single oral dose of mefenamic acid significantly depressed plasma thyroxine (T4) within 3 h in man. Similarly, mefenamic acid depressed plasma T4 within 3 h in thyroidectomized, T4‐maintained rats.

2. Plasma free fractions of T4 and tri‐iodothyronine (T3) increased significantly after a single oral administration of mefenamic acid in man. In vitro addition of mefenamic acid to plasma also increased the plasma free fraction of T4.

3. Three times more T3 was excreted into urine after an acute administration of mefenamic acid.

4. In vitro conversion of T4 to T3 by liver homogenate was stimulated when T4 was displaced from plasma binding protein by mefenamic acid.

5. Pituitary content of T3 increased when mefenamic acid displaced T4 and T3 from the binding protein. Simultaneously, thyrotropin (TSH) secretion in response to thyrotropin releasing hormone (TRH) was completely blocked by mefenamic acid.

6. Prolactin release in response to TRH and luteinizing hormone (LH) and follicle stimulating hormone (FSH) release in response to luteinizing hormone releasing hormone (LH‐RH) were not affected by mefenamic acid.

7. It is concluded that mefenamic acid displaces T3 and T4 from their plasma binding protein and more T4 and T3 are available to peripheral tissues for excretion, degradation and TSH regulation.
FURTHER STUDIES ON NEOMYCIN AND EXPERIMENTAL HYPERTENSION
Authors: Fraillon Danielle , Wynne Ken. N. , Funder John W.
Published: June 2007

1. Acute glucocurticoid (corticosterone) hypertension in the rat is significantly attenuated by neomycin administration (Honour 1981), as is ACTH‐induced hypertension is the same species (Honour & Kent 1981) presumably by altering gut bacterial steroid metabolism.

2. The effect on blood pressure of oral neomycin administration was therefore examined in hypertension resulting from administration of a variety of glucocorticoid hormones.

3. Neomycin significantly attenuated the elevation of blood pressure following ACTH or corticosterone, as previously shown, or prednisolone 1 mg/day; it did not affect blood pressure in rats given dexamethasone 0.2 mg/day, or cortisol 4 mg twice daily.

4. Since the differential effect of neomycin on hypertension parallels neither pressor nor glucocorticoid activity of the administered steroids we propose that it reflects different patterns of enterohepatic handling and metabolism.
VASOCONSTRICTOR EFFECTS OF URIDINE AND ITS NUCLEOTIDES AND THEIR INHIBITION BY ADENOSINE
Authors: Macdonald Graham , Assef Rhonda , Guiffre Ann , Lo Ed
Published: June 2007

1. Uridine, uridine monophosphate (UMP) and uridine diphosphate (UDP) increased blood pressure when infused into intact anaesthetized rats and had similar effects on the perfusion pressure in the rat isolated perfused kidney.

2. In an isolated vascular preparation, the everted rat portal vein, uridine was without effect while UMP and UDP caused log dose‐related increases in contractile work.

3. Adenosine infused at a dose of 200 nmol/kg per min blocked the response to uridine in the intact rat, converting it to a depressor response at higher doses, and reduced the response to UMP.

4. Uridine may need to be phosphorylated to UMP to act on blood vessels. The two compounds are effective at similar dose ranges and suppress renin secretion in the isolated kidney, while UDP, which is effective at lower doses and stimulates renin secretion, may act by a different mechanism.

5. Adenosine competes for membrane transport with uridine but its inhibition of the effects of UMP is consistent with activity at intracellular sites as well.
ROLE OF PROSTAGLANDINS DURING REVERSAL OF ONE‐KIDNEY, ONE‐CLIP HYPERTENSION IN THE RAT
Authors: Vandongen Robert , O'Dwyer Julie , Barden Anne
Published: June 2007

1. Unclipping the one‐kidney, one‐clip rat returned blood pressure to normotensive levels within 24 h and was associated with a substantial increase in urinary PGE2 and 6‐keto PGF1α excretion.

2. Prior treatment with indomethacin (6.0 mg/kg) markedly reduced urinary prostaglandins after clip removal and attenuated the fall in blood pressure. Aspirin (100 mg/kg) treatment, which reduced 6‐keto PGFα to a lesser degree without altering PGE2 excretion, had no significant effect on the blood pressure fall.

3. It is suggested that in the one‐kidney, one‐clip rat prostaglandins are released as the result of exposing the unclipped kidney to elevated arterial pressure, and that these contribute to the subsequent fall in blood pressure.
LOCALIZATION OF ANGIOTENSIN CONVERTING ENZYME IN RAT FOREBRAIN AND OTHER TISSUES BY IN VITRO AUTORADIOGRAPHY USING 125‐I‐LABELLED MK351A
Authors: Mendelsohn F. A. O.
Published: June 2007

1. The potent angiotensin converting enzyme inhibitor, MK351A, was radioiodinated and found to show saturable, high affinity, reversible binding to membrane fractions of rat lung. At 20°C the labelled inhibitor bound to lung membranes with a T½ of ≏ 2–3 min and reached a plateau at 15 min; the complex dissociated with a T½, ≏ 65 min on addition of excess unlabelled MK521.

2. The potency of a series of converting enzyme inhibitors in displacing the radioactive ligand closely paralleled their anticatalytic potency, strongly suggesting that the ligand labels the active site of converting enzyme.

3. This ligand has the desired properties as a probe for autoradiographic localization of converting enzyme since it exhibits high affinity, stable binding to the enzyme with very low non‐specific binding (< 2% of total).

4. In vitro autoradiographic analysis using 125I‐MK351A revealed a very high density of converting enzyme in lung, small bowel mucosa, adrenal zona glomerulosa and medulla and renal cortex. In rat forebrain a very high density of binding was found in the choroid plexus, subfornical organ and caudate‐putamen.

5. This technique provides a promising method for the quantitative localization of angiotensin converting enzyme in tissues.
DEVELOPMENT OF ANGIOTENSIN CONVERTING ENZYME IN FETAL LUNG AND PLACENTA OF THE RAT AND HUMAN
Authors: Sim M. K. , Seng K. M.
Published: June 2007

1. Angiotensin converting enzyme (ACE) activity in fetal lung and placenta was determined by the method of Cushman and Cheung (1971) during the second trimester of human pregnancy and throughout the rat gestation. The enzyme activity in the neonatal rat lung was also determined during the first 19 days of life.

2. The enzyme activity in both tissues of both species increased with gestation. The activity in human fetal lung at the end of the second trimester was already 70% of that present in the adult human lung while rat fetal lung enzyme activity at term was only 15% of the adult value. The activity in the term placenta of the human and rat was respectively 13% and 5% that of the adult lung value. Developmental increases in enzyme activity continued in the neonatal rat lung till adult value at about 19 days postpartum.

3. The pattern of fetal lung enzyme development in the rat resembled that of the rabbit fetal lung as determined by other investigators using different techniques but was different from that of the human.

4. The findings support the suggestion that ACE in the lung and placenta play important roles in the maintenance of circulatory homeostasis during the latter part of gestation, at birth and early postpartum, albeit at a different extent in different species.
ALTERATIONS IN CEREBROSPINAL FLUID SODIUM AND OSMOLALITY IN RATS DURING ONE‐KIDNEY, ONE‐WRAP RENAL HYPERTENSION
Authors: Haywood J. R. , Buggy J. , Fink G. D. , DiBona G. F. , Johnson A. K. , Brody M. J.
Published: June 2007

1. Measurements of plasma and cerebrospinal fluid (CSF) sodium and osmolality were made throughout the course of one‐kidney, one‐wrap Grollman renal hypertension.

2. Although the plasma sodium and osmolality did not rise after 28 days, CSF sodium and osmolality was increased significantly at 3 days postwrap.

3. As a result, the CSF to plasma ratio for both sodium and osmolality was significantly elevated during the initial postwrap period.

4. These observations suggest that an increase in CSF sodium may provide an initiating stimulus for an elevated arterial pressure in one‐kidney, one‐wrap renal hypertension.
THE MEASUREMENT OF PLASMA THROMBOXANE B2 AND THE EFFECT OF SMOKING
Authors: Sturm M. , Barden A. , Beilin L. J. , Taylor R. R.
Published: June 2007

1. Plasma thromboxane B2 (TxB2) was measured by radioimmunoassay using an iodinated ligand following extraction and further purification by thin layer chromatography. Venous blood was sampled into a syringe containing the cyclooxygenase inhibitor meclofenamate.

2. Normal levels, 15 pg/ml (s.d. = 8, n= 21), were lower than usually reported and measured values increased several fold over 20 min sampling from an indwelling needle.

3. With appropriate sampling there was a statistically insignificant increase in plasma TxB2 after subjects smoked two cigarettes (n= 11). An average decrease occurred in a control group (n= 10) and the difference between groups was of borderline significance (P<0.05). Smoking did not change TxB2 production associated with platelet aggregation induced in vitro by collagen, whereas plasma adrenaline increased significantly.

4. The results emphasize the importance of the technique of sampling and assay in the measurement of plasma TxB2.
A COMPARISON OF THE EFFECTS OF SALBUTAMOL, ETILEFRINE AND DEXTRAN DURING HYPOTENSION AND LOW CARDIAC OUTPUT STATES IN RABBIT
Authors: Adigun S. A. , Fentem P. H.
Published: June 2007

1. The effects of salbutamol (25 and 50 μg/kg), etilefrine (50 and 200 μg/kg) and dextran (8 ml/kg) on cardiovascular function have been studied in the rabbit.

2. The three drugs raised the resting cardiac output (with salbutamol producing Δ max 52%, P<0.001, n=5) and right heart filling pressure (RHFP, Δ max from dextran 3.5 cmH2O; P<0.001, n=6) and lowered total peripheral resistance (TPR, Δ max from salbutamol 46%, P<0.001, n=5). However, TPR rose with the 200 μg/kg etilefrine (P<0.05, n=5). Pulse pressure rose with salbutamol (P<0.001, n=6) and etilefrine (P<0.05, n=6). Etilefrine raised resting BP (Δ max, P<0.001, n=6); salbutamol lowered resting BP (Δ max, P<0.001, n=6) while dextran (n=6) had little effect on resting BP.

3. The actions of salbutamol are mediated mainly through β2‐adrenoceptors although the drug also has some minor β1‐adrenoceptor action. With etilefrine, the increase in cardiac output and the reduction in TPR are mediated through (β‐adrenoceptors while the increases in RHFP, blood pressure and TPR are a direct action on the α‐adrenoceptors.

4. However, during haemorrhage the fall in diastolic pressure produced by salbutamol was considerably reduced while the reduction in mean BP and systolic pressure (which sometimes rose) was abolished. Dextran raised BP during hypotension produced by either sympathectomy or haemorrahge but not during normotension.

5. The reflex recovery in RHFP and the reflex tachycardia were slightly attenuated during lower body negative pressure (LBNP) after salbutamol or dextran. The reflex recovery in blood pressure was complete and the pressure sometimes exceeded the resting level by up to 10 mmHg during LBNP after salbutamol, etilefrine (50 μg/kg only) and dextran.

6. The reduced TPR (presumably due to vasodilation) and the increases in cardiac output and RHFP at an adequately maintained blood pressure produced by suitable doses of the three drugs may be useful in the management of circulatory shock and related states.
INTERACTION OF CHOLINE WITH NICOTINIC AND MUSCARINIC CHOLINERGIC RECEPTORS IN THE RAT BRAIN IN VITRO
Authors: Costa Lucio G. , Murphy Sheldon D.
Published: June 2007

1. The ability of choline to interact with nicotinic receptors was investigated by measuring its ability to inhibit the specific binding of [3H]‐nicotine in rat brain.

2. Choline, with an IC50 of 241 μmol/l, was three times more potent than its analogue deanol and almost 1000‐fold less potent than acetylcholine.

3. Choline also inhibited the binding of the antagonist [3H]‐quinuclidinyl benzilate (IC50=2.5 mmol/l) and of the agonist [3H]‐oxotremorine‐M (IC50=165 μmol/l) to muscarinic cholinergic receptors.

4. These results indicate that choline is able to interact directly, in vitro with brain cholinergic receptors of both the nicotinic and muscarinic type.
PARADOXICAL CARDIOVASCULAR RESPONSE TO VISCERAL AFFERENT STIMULATION IN THE ESTABLISHED SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Koyama Shozo , Manning John W.
Published: June 2007

1. Afferent splanchnic nerve stimulation with different frequencies in Wistar Kyoto rats caused depressor and pressor responses depending on the frequency employed.

2. Similar visceral afferent activation in spontaneously hypertensive rats caused depressor responses at all frequencies of stimulation.

3. It is suggested that the central integrated mechanisms for activating a cardiovascular state change as evoked by visceral afferents may differ in the established hypertensive rat from that of the normotensive.
FURTHER STUDIES ON THE EFFECTS OF ADRENAL STEROIDS IN THE ACTIVE TRANSPORT OF SEROTONIN INTO RAT PLATELETS
Authors: Lee P. H. K. , Chan Mo‐Yin
Published: June 2007

1. Male rats were treated with a fixed dose of aminoglutethimide (50 mg/kg s.c.) or with progressively increasing doses (50‐100 mg/kg s.c.) for 3 days. Corticosterone levels were found to be decreased in the latter group. Platelet uptake of serotonin as well as the apparent Vmax were decreased, whereas the Km of uptake were increased when compared with that of the control group.

2. Addition of ACTH (10 iu/dl) to control rat platelet and corticosterone (10‐80 μg/dl) or triamcinolone (0.5‐5.0 μg/dl) to adrenalectomized rat platelet suspension in vitro did not increase the serotonin uptake of the preparation.

3. Administration of exogenous dexamethasone (0.05‐0.2 mg/kg i.m.) or triamcinolone (0.05‐5.0 mg/kg i.m.) to adrenalectomized rats, caused a dose related increase in active uptake of serotonin by the platelets. Deoxycorticosterone (0.1‐1.0 mg/kg i.m.) did not have this effect.

4. The time course of response to, and the maximum percentage increase in platelet serotonin uptake by, exogenous corticosteroids are related to their glucocorticoid potency.

5. The possible role of glucocorticoids on platelet serotonin uptake process is discussed.
CHOLINERGIC NEUROMODULATION BY ATP, ADENOSINE AND ITS N6‐SUBSTITUTED ANALOGUES IN GUINEA‐PIG ILEUM
Authors: Katsuragi T. , Furuta K. , Harada T. , Furukawa T.
Published: June 2007

1. The effects of ATP, adenosine and N6‐substituted adenosines, adenosine receptor agonists, on the twitch contraction of guinea‐pig ileum evoked by transmural stimulation were evaluated.

2. Adenosine and ATP produced an immediate and concentration dependent inhibition of the twitch, IC50 being 1.1 × 10−5 mol/l and 1.2 × 10−5 mol/l, respectively.

3. N6‐l‐phenylisopropyl adenosine (L‐PIA), N6‐cyclohexyl adenosine (CHA) and N6‐allyl adenosine also induced inhibitions which were gradual and persistent, IC50 being 2.6 × 10−8, 2.7 × 10−8 and 5.4 × 10−7 mol/l, respectively.

4. Dipyridamole (10−7 mol/l), an adenosine uptake inhibitor, markedly augmented the inhibition evoked by adenosine and ATP, but not that by three N6‐substituted adenosines, while theophylline (10−4mol/l) almost completely antagonized the inhibitory effects of all purine compounds. IC50 value of adenosine in the presence of dipyridamole (5 × 10−7 mol/l) was shifted to the left about 50 times from the control, whereas that of L‐PIA was virtually unchanged.

5. Tissue‐medium ratios indicating uptake of [H]adenosine, [3H]ATP and [3H]CHA into the segment were 3.23 (s.e.m. =0.59), 3.59 (s.e.m. =0.78) and 0.41 (s.e.m. =0.04), respectively.

6. These results suggest that not only adenosine and ATP but also these N6‐substituted adenosines are potent agonists for the PI receptor, implying a similarity between PI and A, receptor in a functional role and these purine compounds may thereby modulate cholinergic neurotransmission by altering adenylate cyclase activity.
REGIONAL O2 SUPPLY/CONSUMPTION IN NORMAL AND ISCHAEMIC RABBIT MYOCARDIUM: EFFECT OF NIFEDIPINE
Authors: Eliades Diane , Talafih Khalid , Weiss Harvey R.
Published: June 2007

1. The effect of nifedipine infusion on myocardial O2 supply and consumption in flow‐restricted and normal regions of the left ventricle was tested in anaesthetized open‐chest rabbits after ligation of the left anterior descending coronary artery for one hour.

2. Ten min after occlusion, nifedipine‐treated animals were given either a low or high dose of the drug: a 5 μg/kg bolus followed by 1 μg/kg per min infusion or a 10 μg/kg bolus and 10 μg/kg per min infusion, respectively. Regional blood flow was measured before and after occlusion using radioactive microspheres and O2 saturation was measured microspectrophotometrically; the Fick Principle was then employed to determine regional O2 consumption.

3. After a 60 min occlusion, blood flow was reduced overall to 51% of pre‐ligation flows in the occluded region, and treatment with nifedipine or vehicle did not significantly alter this flow reduction.

4. Blood flow in nonoccluded regions increased 1.6‐fold only with the high dose of nifedipine and was unchanged in all other groups.

5. Microspectrophotometric analysis of low dose nifedipine and control hearts showed that O2 extraction was greater in occluded than in normal myocardium (9.0, s.d. = 0.9, ml O2/100 ml blood vs 7.2, s.d. = 0.7, respectively) and that subendocardial extraction exceeded subepicardial.

6. These data suggest that nifedipine administration at this dose had no apparent beneficial effect on O2 supply or O2 consumption in normal or flow‐restricted regions of the left ventricle during 1 h of coronary artery occlusion.
THE EFFECTS OF NIFEDIPINE ON THE SYSTEMIC AND CORONARY VASCULAR BEDS OF THE SHEEP: A POTENTIAL METHOD FOR INDUCTION OF ISCHAEMIA
Authors: Fu W. K. , Yong A. C. , Gangell P. , Roberts M. S. , Kilpatrick D.
Published: June 2007

1. Nifedipine has been reported to aggravate symptoms of ischaemic heart disease in some patients. To investigate the possible reasons for this, vascular resistance changes in the systemic and coronary beds of sheep were compared with and without coronary artery stenoses.

2. In six anaesthetized sheep, the dose‐response curve comparing vascular resistance to nifedipine dose showed greater sensitivity than that reported for either dogs or humans. The coronary vascular bed was more reactive than the systemic vascular bed but this difference did not reach a level of statistical significance.

3. With fixed non‐elastic proximal coronary artery stenoses, the relationship of both coronary flow and coronary resistance to a standard dose of nifedipine (5 μg/kg) was indirectly related to the degree of stenosis. With stenosis reducing flow at rest by 50% or more, nifedipine usually produced a reduction in coronary flow in the stenosed artery and associated ST elevation, consistent with severe ischaemia in the distribution of the coronary. This effect is related to the reduction in perfusion pressure.
AN INVESTIGATION OF THE RECEPTORS INVOLVED IN THE CORONARY VASODILATORY EFFECT OF ADENOSINE ANALOGUES
Authors: Leung Edward , Johnston Colin I. , Woodcock Elizabeth A.
Published: June 2007

1. The coronary vasodilatory effect of stable adenosine analogues is mediated by adenosine A2 receptors.

2. These coronary receptors differ from A2 receptors found in other tissues.
ACTIONS OF THE SLOW CHANNEL ACTIVATOR, BAY‐K‐8644, ON THE ELECTRICAL ACTIVITY OF 3‐DAY‐OLD EMBRYONIC CHICK HEARTS
Authors: Sada H. , Sada S. , Sperelakis N.
Published: June 2007

1. In order to assess the effects of Bay‐K‐8644 on electrical activities of young embryonic chick hearts in which the rising phase of the action potential (AP) depends on tetrodotoxin‐insensitive slow Na+ currents, slow AP were recorded in spontaneously beating 3‐day‐old embryonic chick hearts.

2. Bay‐K‐8644(10‐6 mol/l) caused increases in the maximum rate of rise, amplitude, and duration of the slow AP; there was a slow increase in the spontaneous firing rate.

3. Thus, Bay‐K‐8644 stimulates Na+ influx through TTX‐insensitive slow channels.