bluuebunny/crossref_metadata_2025 huggingface dataset:
ANTAGONISM OF PENTOBARBITONE SLEEP BY DOPAMINE, LEVODOPA AND APOMORPHINE IN CHICKS
Authors: Osuide G. , Wambebe C.
Published: June 2007

1. The influence of dopamine, levodopa and apomorphine on sleep produced by pentobarbitone was studied in 1‐14 day old chicks.

2. Pentobarbitone‐induced sleep was associated with synchronization of the electroencephalogram (EEG) of the hyperstriatum, optic tectum and pontine reticular formation.

3. Dopamine desynchronized the EEG and antagonized pentobarbitone‐induced EEG synchronization.

4. High doses of dopamine produced a delayed sleep which was potentiated by pimozide and antagonized by adrenoreceptor blocking agents.

5. Dopamine, levodopa and apomorphine delayed the onset and shortened the duration of pentobarbitone‐induced sleep; apomorphine was the most potent.

6. Pimozide prolonged the duration of pentobarbitone‐induced sleep, but had less effect when dopamine was also given.
EFFECT OF CORTISOL‐INDUCED INHIBITION OF EXTRANEURONAL UPTAKE ON RESPONSES TO ISOPRENALINE IN THE KITTEN
Authors: Goldie R. G.
Published: June 2007

1. In anaesthetized kittens, Cortisol (16 mg/kg) potentiated peak chronotropic responses to isoprenaline but did not affect peak bronchodilator responses to this amine.

2. In contrast, the duration of both chronotropic and bronchodilator effects of isoprenaline were clearly potentiated by Cortisol.

3. These results have been linked with cortisol‐induced inhibition of 3H‐iso‐prenaline uptake in the perfused kitten heart and isolated tracheal smooth muscle.
MAINTENANCE OF PSEUDOPREGNANCY BY PROLACTIN IN INDOMETHACIN TREATED RATS
Authors: Tan G. J. S.
Published: June 2007

1. The effects of bromocriptine and indomethacin on prolactin‐induced pseudopregnancy were studied in pituitary grafted rats.

2. Administration of bromocriptine (a prolactin suppressant drug) at a total dose of 3 mg/kg body weight, given in 3 divided doses on day 5 of pseudo‐pregnancy, effectively terminated it within 3 days. However, injection of indomethacin (a prostaglandin inhibitor) at a total dose of 6 mg/kg body weight, given in 3 divided doses, on the same day of pseudopregnancy had no significant effect on its duration.

3. It appears unlikely that the luteotrophic effect of prolactin on the corpus luteum is mediated by the stimulation of prostaglandin synthesis.
FURTHER INVESTIGATIONS ON THE INTERACTION BETWEEN α‐ADRENOCEPTOR ANTAGONISTS AND THE CENTRAL HYPOTENSIVE EFFECT OF CLONIDINE IN RATS, RABBITS AND DOGS
Authors: Tsoucaris‐Kupfer Danita , Bogaievsky Dominique , Schmitt H.
Published: June 2007

1. The interactions between five α‐adrenoceptor blocking agents and clonidine have been studied in rats, rabbits and dogs after intracisternal injections.

2. Dibozane, ethomoxane, azapetine, dibenamine and thymoxamine reduced blood pressure in rats and an antagonism of the hypotensive effects of clonidine was detected for the first four drugs.

3. In rabbits, azapetine, dibenamine, dibozane and ethomoxane were hypotensive while thymoxamine had no effect on blood pressure. Dibozane and dibenamine reduced the hypotensive effect of clonidine.

4. In dogs, azapetine, dibozane and ethomoxane reduced blood pressure, while dibenamine induced an increase in blood pressure and thymoxamine was without effect. Only dibenamine antagonized the blood pressure lowering effect of clonidine. A definite conclusion could not be drawn with azapetine due to its long duration of action in both rabbits and dogs.

5. These results suggest that the central receptors involved in the hypotensive effect of clonidine differ from many other central receptors and vary according to the animal species. In addition the a‐adrenoceptor blocking agents appear not to have a unique site and mechanism of action on central cardiovascular control.
PROSTAGLANDIN RELEASE BY ALIPHATIC ALCOHOLS FROM THE RAT ISOLATED LUNG
Authors: Thomas Molly , Boura A. L. A. , Vijayakumar Ramana
Published: June 2007

1. A comparative study has been made of the abilities of members of a homologous series of aliphatic alcohols to release prostaglandins from the rat isolated perfused lung.

2. Infusions of low concentrations (0002 mmol‐0‐2 mmol) of methyl, ethyl, n‐propyl, i‐propyl, n‐butyl and t‐butyl alcohol for periods of up to 5 min was accompanied by the continuous output of prostaglandins into the venous effluent, as measured by biological assay. Maximal release occurred with methyl and ethyl alcohols, the releasing abilities of the rest being in the order of n‐propyl > i‐propyl > n‐butyl >> t‐butyl. Radioimmunoassay revealed that both PGE2 and PGF2α were released by ethyl alcohol with the former being in up to 10 times greater quantities than the latter. However, the amounts of these prostaglandins failed to account for the total release of active substances as measured by bioassay.

3. Examination of concentration‐response relationships showed that as the concentration of methyl, ethyl and n‐propyl alcohol was increased prostaglandin output also increased, but that after reaching a maximum further increase in alcohol concentration resulted in diminished release. In contrast, the lowest concentration of i‐propyl, n‐butyl and t‐butyl alcohol utilized (0002 mmol) caused highest prostaglandin output and release declined as the concentration was increased. Release by ethyl alcohol (002 mmol) was inhibited by t‐butyl alcohol (0‐2 mmol).

4. Thus aliphatic alcohols can not only release prostaglandins but also depress release. Both properties appear to be possessed by each member of the series, their relative prominence varying in each compound. Release is the predominant action of the low molecular weight, short chain compounds whereas depression of release is the most prominent property of those of higher molecular weight, particularly the secondary and tertiary alcohols.

5. It is suggested that release occurs in response to low alcohol concentrations altering the nature of the water‐cell membrane interface, thus producing changes in membrane protein configuration and activation of phospholipase A. Inhibition of release is probably a consequence of non‐specific depression of cell function.
TIENILIC ACID IN THE TREATMENT OF MILD TO MODERATE HYPERTENSION
Authors: Walker R. G. , Yeung C. K. , Hua A. S. P. , Thomas G. W. , Whitworth Judith A. , Kincaid‐Smith Priscilla
Published: June 2007

1. A double‐blind crossover trial comparing the antihypertensive effect of tienilic acid and hydrochlorothiazide was conducted in thirty‐eight patients with mild to moderate hypertension.

2. Tienilic acid was shown to be as effective as hydrochlorothiazide in controlling blood pressure.

3. Tienilic acid significantly lowered serum uric acid levels compared with both placebo and hydrochlorothiazide.

4. Tienilic acid was generally well tolerated but one patient developed acute renal failure due to acute allergic interstitial nephritis whilst taking the drug.
THE EFFECT OF INTRAVENOUS ADMINISTRATION OF GABA AND BRAIN EXTRACTS ON BLOOD PRESSURE IN THE RAT
Authors: Horvath J. S. , Baxter Claire R. , Duggin G. , Tiller D. J.
Published: June 2007

1. A rat bioassay was used to study pressor substances in brain extracts.

2. A compound with pressor activity in pentolinium‐treated rats was extracted from brain, purified using Dowex, Sephadex electrophoresis and identified as γ‐aminobutyric acid (GABA) by HPLC and mass spectrometry.

3. Intravenous GABA (1‐5 μg) or brain extracts caused a dose dependent decrease in blood pressure in pentobarbitone‐anaesthetized rats.

4. After ganglion blockade with pentolinium (2 mg/kg subcutaneously), GABA or brain extracts cause a dose dependent increase in rat blood pressure.

5. This pressor effect is reduced by α‐ and β‐blockers (intravenous phentol‐amine, 0‐5 mg/kg and propranolol, 005 mg/kg).

6. It is concluded that GABA causes a fall in blood pressure by a central mechanism and ganglion blockade unmasks a pressor effect.
ACUTE CHANGES IN BLOOD PRESSURE AND VASOACTIVE HORMONES AFTER CAPTOPRIL IN HYPERTENSIVE PATIENTS
Authors: McGrath Barry P. , Matthews P. Geoffrey , Johnston Colin I.
Published: June 2007

1. The acute effects of captopril on blood pressure, renin, angiotensin, bra‐dykinin and catecholamines were examined in patients with essential (n= 10, Group 1), accelerated (n=6, Group 2) and renal hypertension (n= 14, Group 3).

2. Blood pressure showed little change in Group 1, fell significantly in Group 2, with a marked fall in Group 3. Heart rate did not change.

3. The fall in blood pressure was positively correlated with pretreatment renin and angiotensin II.

4. Angiotensin II fell, with reciprocal increases in renin and angiotensin I. No changes occurred in bradykinin or catecholamines.

5. The rise in renin after captopril was greatest in renovascular hypertension which may prove useful as a screening test for such patients.
RENAL, ADRENAL AND VASCULAR CHANGES DURING INHIBITION OF CONVERTING ENZYME WITH CAPTOPRIL
Authors: Clappison B. H. , Millar J. A. , Casley D. J. , Anderson W. P. , Johnston C. I.
Published: June 2007

1. In rats treated continuously with captopril (80 μg/h, i.p.), for 2 days, blood pressure decreased and adrenal angiotensin II receptor concentration was decreased from 160 fmol/mg protein (s.e.m.=9) in controls to 131 fmol/mg protein (s.e.m. = 7, P < 0.01, n= 10). However, after 5 days of continuous treatment, blood pressure had returned to normal and adrenal receptor concentrations in treated rats were not significantly different from controls (180 fmol/mg, s.e.m. = 11 and 203 fmol/mg protein s.e.m. = 14 respectively, 0.1>P>005).

2. Vascular reactivity, defined as the pressor response to exogenous angiotensin II, increased concurrently by 166 and 33% respectively.

3. In anaesthetized dogs (n= 8), captopril (1.5 mg/kg, i.v.) caused a fall in blood pressure, and urine bradykinin excretion increased from 1 08 (s.e.m.=0 14) to 1 64 μg/h (s.e.m.=0 33, P < 0 025) at 15 min. Renal blood flow increased significantly (P < 0 01) with no change in glomerular filtration rate, and there was no change in either renal venous or arterial blood bradykinin levels.

4. Thus, converting enzyme inhibition produces transient secondary changes in angiotensin receptors and vascular reactivity. Increased urine bradykinin probably reflects decreased catabolism of intrarenal bradykinin. The hypotensive effect of captopril may be due in part to raised levels of bradykinin in the kidney.
COMPARISON OF INITIAL RESPONSES TO RENAL ARTERY STENOSIS IN PENTOBARBITONE–ANAESTHETIZED AND CONSCIOUS DOGS
Authors: Anderson W. P.
Published: June 2007

1. Trained chronically‐instrumented dogs were subjected to renal artery stenosis twice. A 50 mmHg stenosis pressure gradient was established while the dogs were conscious or anaesthetized with pentobarbitone and prepared for renal surgery.

2. Prior to stenosis, the anaesthetized dogs had significantly higher mean arterial pressure, renal vascular resistance and plasma renin activity than when they were conscious.

3. Twenty‐four hours after stenosis, when all dogs were fully conscious, significant elevations in mean arterial pressure and plasma renin activity were seen only in the dogs anaesthetized for stenosis production. Creatinine clearance over this period was also markedly less than after renal artery stenosis of conscious animals.

4. It seems likely that more severe renal artery stenosis is required to produce a given pressure gradient in anaesthetized dogs than in the conscious dogs.
THE PRESENT STATUS OF THE AUTOREGULATION THEORY OF THE PATHOGENESIS OF HYPERTENSION
Authors: Korner P. I.
Published: June 2007

1. The autoregulation theory of hypertension has been attractive because it postulates a mechanism whereby an early rise in cardiac output becomes ‘transformed’ through normal autoregulatory processes into an elevated total peripheral resistance.

2. ‘Normal’ autoregulation involved in control of blood flow of regional beds is a rapid process compared with the slow changes postulated by the autoregulation theory.

3. Evidence is presented that under appropriate experimental conditions ‘volume’ factors (cardiac output) and ‘constrictor’ factors exert independent long‐term effects in developing and in established hypertension. There is little evidence to support the autoregulation theory of hypertension.
HYPOTENSIVE EFFECTS OF CAPTOPRIL ADMINISTERED CENTRALLY IN INTACT CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS AND PERIPHERALLY IN ANEPHRIC ANAESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Hutchinson J. S. , Mendelsohn F. A. O.
Published: June 2007

1. The hypotensive response to captopril in anaesthetized spontaneously hypertensive rats (SHR) is not modified by bilateral nephrectomy performed 1 or 24 h previously.

2. Intracerebroventricular injection (i.c.v.) of captopril (2 mg kg−1) significantly lowered blood pressure of conscious SHR over a 7‐h period of observation but there was no significant blood pressure response to i.c.v. vehicle, or to intravenous captopril (2 mg kg−1) in SHR.

3. There was no significant blood pressure response to captopril (2 mg kg”') i.c.v. in the normotensive Wistar Kyoto controls (NT‐WK).

4. These results indicate that captopril can lower the blood pressure of SHR by mechanisms independent of the kidneys or the circulating renin‐angiotensin system.

5. The hypotensive effect of central captopril in SHR but not in the NT‐WK suggests biochemical differences between the brains of the two rat strains.
FACILITATION OF SYMPATHETIC TRANSMISSION BY PREJUNCTIONAL β‐ADRENOCEPTORS IN CARDIAC AND VASCULAR TISSUES
Authors: Medgett I. C. , McCulloch M. W. , Rand M. J. , Story D. F.
Published: June 2007

1. In rat isolated tail arteries and atria in which transmitter stores are labelled with (3H)‐noradrenaline, isoprenaline in low concentrations facilitates the stimulation‐induced efflux of tritium.

2. This effect is dependent on the frequency and duration of electrical stimulation, being observed only at low frequency (2 Hz) and short duration (10 s in atria and 30 s in arteries) or at high frequency (5 Hz) and long duration (1 min in atria and 4 min in arteries).

3. In atria, phentolamine enhances tritium efflux with stimulation at 5 Hz for 1 min but not at 2 Hz for 10 s. Conversely, propranolol reduces tritium efflux with stimulation at 2 Hz for 10 s but not at 5 Hz for 1 min.

4. The results can be interpreted in terms of the selective operation, depending on the frequency and duration of electrical stimulation, of inhibitory and facilitatory feedback loops for transmitter release involving prejunctional a‐and β‐adrenoceptors, respectively.
THE INFLUENCE OF DIETHYL MALEATE ON THE BILIARY EXCRETION OF INFUSED SULPHOBROMOPHTHALEIN SODIUM AND ITS GLUTATHIONE CONJUGATE IN GUINEA‐PIGS
Authors: Whelan Gregory
Published: June 2007

1. Hepatic sulphobromophthalein (BSP) transport was studied in guinea‐pigs pretreated intraperitoneally with 0 7 ml of diethyl maleate to depress hepatic glutathione levels.

2. Diethyl maleate depressed the hepatic transport of infused conjugated BSP from hepatocytes into bile without influencing hepatic uptake.

3. Unconjugated BSP transport was also depressed markedly as a result of (a) a reduction in the intrahepatic conjugation of BSP with glutathione and (b) suppression of conjugated BSP excretion.
SYSTEMIC AND REGIONAL HAEMODYNAMICS IN EXPERIMENTAL RENAL HYPERTENSION IN CONSCIOUS RABBITS
Authors: van Boom Martin , Saxena Pramod R.
Published: June 2007

1. The radioactive microsphere method was used to measure the distribution of cardiac output, regional flows and resistances in conscious normotensive and hypertensive rabbits implanted with an electromagnetic flow probe on the ascending aorta or pulmonary artery. Hypertension was induced by wrapping one kidney with cellophane and removing the other, and studies were performed about 5 weeks later.

2. Heart rate, stroke volume, cardiac output and total renal mass were reduced in the hypertensive animals, while the weight of, and the cardiac output distribution to left ventricle and the remaining kidney were increased.

3. In renal hypertensive rabbits, the weight normalized regional blood flow was diminished in a number of tissues, including the kidney, and, except for some organs in the splanchnic area (stomach, small intestine, mesentery and pancreas) and the fat, there was a rather uniform increase in tissue vascular resistance.
THE HYPOTENSIVE RESPONSE TO COMPOUND 48/80 IN NORMOTENSIVE AND HYPERTENSIVE RATS
Authors: Kirkendol Paul L. , Cauvin Cynthia A.
Published: June 2007

1. The administration of an initial dose of 50 μg/kg of 48/80 produced a sharp fall in the blood pressure of normotensive rats but produced little change in blood pressure in spontaneously hypertensive rats.

2. The administration of an additional 50 μg/kg and 100 μg/kg of 48/80 in normotensive and spontaneously hypertensive rats resulted in equivalent decreases in pressure in both groups.

3. Both groups had equivalent decreases in blood pressure in response to methylhistamine.

4. Spontaneously hypertensive rats appear to have a reduced ability to release histamine in response to 48/80 due to either an increased threshold for 48/80 or a diminished histamine storage pool.
BOOK REVIEWS
Authors: Doyle A. E. , Bowman W. C. , Yeomans Neville D.
Published: June 2007

Cardiovascular Drugs. Volume 4, Antihypertensive Drugs Today. Ed. by R.N. Brogden.

Cross‐Bridge Mechanism in Muscle Contraction. Ed. by Haruo Sugi and Gerald H. Pollack.

Glucagon in Gastroenterology. Edited by J. Picazo.
IN‐VIVO MODIFICATION OF ANGIOTENSIN 11 PRESSOR RESPONSIVENESS IN SHEEP BY INDOMETHACIN
Authors: Beilby David S. , Coghlan John P. , Denton Derek A. , Graham William F. , Humphery Timothy J. , Scoggins Bruce A. , Whit worth Judith A.
Published: June 2007

1. Sodium (Na) depletion, due to uncompensated loss of parotid saliva, reduces the pressor responsiveness to angiotensin II (AII) in intact conscious sheep.

2. Inhibition of prostaglandin synthesis by indomethacin restored All pressor responsiveness in Na‐deplete sheep.

3. Indomethacin infusion also increased the pressor responsiveness to AII in the Na‐replete sheep.

4. These findings suggest that in vivo prostaglandins may play a role in modulating the pressor responsiveness to angiotensin II in sheep.
ALTERED CARDIAC NORADRENALINE STORES IN DOCA‐SALT HYPERTENSIVE RATS
Authors: Howe P. R. C. , West M. J. , Chalmers J. P.
Published: June 2007

1. The storage of noradrenaline (NA) in hearts of DOCA‐salt hypertensive rats was examined after in vivo administration of labelled NA.

2. The cardiac N A concentration and the neuronal NA storage capacity were reduced in these rats compared with normotensive controls. The extent of reduction was dependent on the duration of hypertension.

3. These findings are similar to observations on spontaneously hypertensive rats and support the hypothesis that storage of the cardiac sympathetic transmitter is impaired in DOCA‐salt hypertension.
A STUDY OF THE EFFECTS OF HYPOTHYROIDISM INDUCED BY PROPYLTHIOURACIL ON ADRENOCEPTORS AND NORADRENALINE LEVELS IN THE VAS DEFERENS OF THE RAT
Authors: Leedham J. A. , Handberg G. M. , Ishac E. J. , Pennefather J. N.
Published: June 2007

1. The anti‐thyroid drug, propylthiouracil (0.05% w/v in drinking water) was administered to rats for 3–4 weeks. This treatment decreased the rate at which rats gained body weight but did not affect the weight of the vasa deferentia. Circulating levels of thyroxine and triiodothyronine were markedly decreased.

2. The potencies of postjunctional α‐adrenoceptor agonists, 1‐noradrenaline and 1‐phenylephrine, in eliciting contraction of the epididymal end of the vas deferens were unaffected by propylthiouracil treatment. In contrast, the potency of the β‐adrenoceptor agonist, 1‐isoprenaline, in inhibiting field stimulation‐induced twitches of the prostatic end of the vas deferens was decreased in tissues from propylthiouracil‐treated rats. Thus hypothyroidism induced by propylthiouracil produced an apparent change in the properties of postjunctional β‐adrenoceptors without a concomitant reciprocal change in the properties of postjunctional α‐adrenoceptors.

3. Treatment of rats with propylthiouracil led to a small increase in the concentration of noradrenaline in the vas deferens, and a concomitant small increase in the rate of accumulation of 3 H‐noradrenaline in in vitro experiments. Extra‐neuronal uptake of 3H‐isoprenaline was unaffected by propylthiouracil treatment.

4. The potencies of the prejunctional α‐adrenoceptor agonists, xylazine and 1‐noradrenaline, in producing inhibition of twitches evoked by field stimulation of preparations of the prostatic end of the vas deferens, were similar in preparations from propylthiouracil‐treated and control rats, although the slope of the log dose‐response curve to xylazine was decreased in the former group. Thus unequivocal changes in the properties of prejunctional α‐adrenoceptors did not accompany the other prejunctional effects of propylthiouracil upon endogenous noradrenaline levels and neuronal uptake of 3H‐noradrenaline in this organ.
INOTROPIC RESPONSES OF ISOLATED ATRIAL AND VENTRICULAR MUSCLE FROM THE DOG HEART TO INOSINE, GUANOSINE AND ADENOSINE
Authors: Chiba Shigetoshi , Watanabe Hidehiko , Furukawa Yasuyuki
Published: June 2007

1. The inotropic effects of inosine, adenosine and guanosine were compared in isolated and blood‐perfused canine atrial and ventricular muscle preparations paced at 1.5 2.5 Hz.

2. In isolated atria, guanosine and inosine usually had positive inotropic effects, but adenosine consistently had a marked negative inotropic effect.

3. In ventricular muscles, the three purine compounds examined produced dose‐related positive inotropic responses, but adenosine also produced a slight negative inotropic response which preceded the positive inotropic response.
EFFECTS OF THYROID HORMONES, ANTITHYROID DRUGS AND IODIDE ON IN VITRO CONVERSION OF THYROXINE TO TRIIODOTHYRONINE
Authors: Aizawa Toru , Yamada Takashi
Published: June 2007

In an attempt to study the effects of thyroid hormones, antithyroid drugs and iodide on the conversion of thyroxine (T4) to triiodothyronine (T3), the liver was obtained from normal, hypothyroid and hyperthyroid rats treated with T4 or T3. T4 was incubated with liver homogenates and generated T3 was measured.

1. The conversion of T4 to T3 was less in the liver homogenates from thyroidectomized, methylmercaptoimidazole (MMI)‐treated and propylthiouracil (PTLT)‐treated rats. The magnitude of decrease was the same in thyroidectomized and MMI‐treated rats, but was greater in PTU‐treated rats.

2. Administration of T4 and T3 to thyroidectomized and MMI‐treated rats restored the converting activity. When excess T4 was administered, the converting activity was above normal. In contrast, administration of graded doses of T4 failed to restore the converting activity of the liver from PTU‐treated rats.

3. In vitro addition of MMI failed to affect converting activity of the liver, but addition of excess iodide and PTU significantly depressed it.
EFFECT OF SUSTAINED HYPERNATRAEMIA ON THE RENIN‐ALDOSTERONE SYSTEM IN THE DOG
Authors: Young David B. , McCaa Robert E.
Published: June 2007

1. To determine if increases in plasma sodium concentration P[Na] have any sustained effects of the renin‐aldosterone system, P[Na] was increased in a group of six dogs over a period of 6 days by increasing sodium intake from 10 to 200 mmol per day while a fixed 700 ml per day water intake was maintained along with a continuous i.v. infusion of antidiuretic hormone (ADH) at a rate of 2.4 units per day.

2. P[Na] rose from 137.3 ± 2.0 to 153.6 ± 6.5 mmol/1 during the high intake period. Plasma potassium concentration, 22Na space, and mean arterial pressure all remained near control levels in response to Na loading.

3. Plasma renin activity (PRA) averaged 1.0 ± 0.1 ngAI/ml per hour on the final low Na day and fell transiently to 0.6 ± 0.2 ngAI/ml per hour on the first day of sodium loading. For the duration of the study it remained at the control level. Plasma aldosterone concentration fell from the low Na level of 15.4 ± 2.4 ng/100 ml to 10.5 ± 1.5 ng/100 ml on the final day of high Na intake.

4. We conclude that increases in P[Na] in the absence of concomitant changes in P[K], 22Na space and MAP do not have a sustained effect on control of renin release but may exert a negative effect on aldosterone secretion.
SERUM CONCENTRATIONS OF DIGOXIN ENTRAPPED IN LIPOSOMES AFTER INTRAVENOUS ADMINISTRATION IN DOGS
Authors: Fountain M. W. , Pedersoli W. D. , Ravis W. R. , Ganjam V. K.
Published: June 2007

1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28–33 mol% in Hank's Buffer, pH 7.4 at 28°C.

2. Digoxin‐liposomes (digoxin concentration 0.022 mg/kg per dog per day) administered intravenously in five adult male dogs attained therapeutic serum concentrations (0.7–3.0 ng/ml) beginning with day 1 of administration.

3. Digoxin serum concentrations obtained by intravenous digoxin‐liposomes compared favorably with normal oral digoxin administration (0.022 mg/kg per dog per day) in all 5 dogs monitoring serum digoxin levels for 7 days showed no significant (P<0.05) differences in mean serum digoxin concentrations ± s.e.m. on 6 of 7 days of treatments.
PIRETANIDE AND URINARY EXCRETION OF IONS IN RAT. EFFECT OF INDOMETHACIN
Authors: Nguyen‐Simonnet H. , Gauthier C. , Pellet M.
Published: June 2007

1. Piretanide is a new loop diuretic resembling furosemide. The effects of this diuretic on various parameters of renal function and on the excretion of the major ions were studied on anaesthetized, hydrated rats.

2. Piretanide induced a marked diuresis and increased sodium, potassium, chloride and calcium excretion. Calcium excretion increased more than that of sodium. Urinary osmolality and water reabsorption decreased.

3. Inulin clearance and phosphate excretion were significantly altered by piretanide.

4. Pretreatment of rats with indomethacin did not suppress the effects of piretanide on diuresis nor its effects on urinary excretion of sodium, chloride and potassium, since these parameters increased in the same proportion in the presence or in the absence of indomethacin.

5. Pretreatment with indomethacin abolished piretanide‐induced dissociation of sodium and calcium excretions.
RESIDUAL CATECHOLAMINES IN EXTRINSICALLY DENERVATED GUINEA‐PIG ILEUM
Authors: Howe P. R. C. , Provis J. C. , Furness J. B. , Costa M. , Chalmers J. P.
Published: June 2007

1. Concentrations of noradrenaline, adrenaline and dopamine were measured in the submucosa and myenteric plexus of innervated and extrinsically denervated guinea‐pig ileum using a sensitive radioisotope enzymatic assay for catecholamines.

2. Subcellular fractionation studies indicated that the microsomal fraction obtained from both layers of the normal ileum was greatly enriched with noradrenaline compared to the total homogenate. Low levels of adrenaline and dopamine were also detected in both layers of the ileum.

3. After extrinsic denervation or pretreatment with reserpine, noradrenaline was reduced to less than 3% and could no longer be visualized histochemically. Small proportions of the adrenaline and dopamine also disappeared after extrinsic denervation.

4. The residual amounts of noradrenaline, adrenaline and dopamine present after extrinsic denervation were not sensitive to reserpine and were not concentrated in microsomal fractions suggesting that these amines are not stored as neurotransmitters in intrinsic neurons of the intestine.
BIOSYNTHESIS OF PREPRORENIN AND INTRACELLULAR CONVERSION OF PRORENIN TO RENIN
Authors: Morris Brian J. , Catanzaro Daniel F.
Published: June 2007

1. The existence of a biosynthetic precursor of renin (prorenin) has been inferred, but never established experimentally. The aim of the present study was to provide this evidence.

2. In a continuous labelling experiment using submandibular glands of male Quackenbush mice (an extraordinarily rich source of renin) a molecule of Mr 44 500 was immunoprecipitated with antiserum to renin.

3. The Mr 44 500 protein was converted to Mr 40 000 renin in a time‐dependent fashion during incubation of tissue at 37Â°C: 15min after addition of [35S] methionine only 16% of immunoprecipitable radioactivity was renin, whereas by 4 h this had increased to 86%. The Mr 44 500 protein would therefore appear to be a ‘pro’ form of renin.

4. Submandibular gland mRNA was translated in a cell‐free system derived from rabbit reticulocyte lysate and a molecule of Mr 46 000 was immunoprecipitated with antirenin. This was preprorenin and the Mr of the ‘pre’ region would thus be 1500, which is consistent with the size generally found for the ‘pre’ region of secretory proteins.

5. The present study has therefore demonstrated for the first time the biosynthesis of a ‘pro’ form of renin (prorenin) and its conversion to renin intra‐cellularly.
EFFECT OF CONVERTING ENZYME INHIBITION WITH CAPTOPRIL ON IN VITRO ANGIOTENSIN PRODUCTION IN SHEEP
Authors: Fei David T. W. , Coghlan John P. , Scoggins Bruce A.
Published: June 2007

1. The effect of captopril on in vitro production of angiotensin I (ANG I), [Val5] ‐angiotensin II ([Vals]‐ANG II) and [Val4]‐angiotensin III ([Val5]‐ANG‐(2–8)) in central venous blood taken from sodium‐deficient sheep was studied.

2. Captopril enhances in vitro production of ANG I but blocks the in vitro production of [Val5] ‐ANG II and [Val5] ‐ANG‐(2–8).

3. The production of ANG I in blood is faster than that of [Val5]‐ANG II and [Val5] ‐ANG‐(2–8).

4. The half‐life of [Val5]‐ANG II and [Val5]‐ANG‐(2–8) in vitro in blood in the presence of captopril was 10 and 14 min, respectively.

5. This in vitro study suggests that the production of [Val5]‐ANG II and [Val5] ‐ANG‐(2–8) in blood forms a small part of the total body production of each peptide.
ADRENALINE SYNTHESIZING NERVE CELLS IN THE MEDULLA OF NORMOTENSIVE AND HYPERTENSIVE RATS
Authors: Chalmers J. P. , Howe P. R. C. , Costa M. , Furness J. , Lovenberg W. , Wallman Y.
Published: June 2007

1. We have studied the number and distribution of adrenaline synthesizing nerve cells in the medulla oblongata of the rat, using a combination of immunofluorescence to visualize the enzyme phenylethanolamine‐N‐methyltransferase (PNMT) and catecholamine fluorescence to detect central catecholamines.

2. The distribution of adrenaline synthesizing nerve cells was similar in normo‐tensive (Wistar Kyoto) rats, spontaneous hypertensive rats, and stroke‐prone rats. Few of the cells visualized by PNMT immunofluorescence were detected by the Faglu fluorescence method for catecholamines. The CI (ventrolateral) and C2 (dorsomedial) groups of PNMT cells were anatomically distinct from the Al and A2 groups of catecholamine fluorescent cells and lay rostral to these cells within the medulla. There was a third group of adrenaline synthesizing cells close to the midline in the rostral medulla, and we have called this the C3 group.

3. There was a 32% increase in the number of PNMT cells in the medulla of 4‐week‐old stroke‐prone rats.

4. PNMT enzyme activity in a cross‐segment of the medulla containing the adrenaline synthesizing cells was also increased by 30% in both spontaneous hypertensive rats and stroke‐prone rats.
RENAL AUTOTRANSPLANTS IN SHEEP: INVESTIGATION OF RENAL FUNCTION AND RENOVASCULAR HYPERTENSION
Authors: McDougall John G. , Coghlan John P. , Denton Derek A. , Fei David T. W. , Hammond Timothy G. , Hardy Kenneth J. , Potocnik Simon J. , Scoggins Bruce A. , Wright R. Douglas
Published: June 2007

1. A novel surgical preparation of sheep with a cervical renal autotransplant has been developed.

2. Glomerular filtration rate and effective renal plasma flow were 25.1 ± 1.0 ml/min and 208 ± 10 ml/min respectively (n= 26).

3. The responses to water load and deprivation, to AVP injection, to Na depletion and intravenous hypertonic saline load show the kidneys responded in an appropriate physiological manner.

4. Constriction of the carotid‐renal artery to reduce mean renal arterial pressure to 23 ± 4 mmHg (n= 4) resulted in an increase in systemic mean arterial pressure from 70 ± 4 mmHg to 75 ± 4 mmHg within 5 min. Systemic blood pressure further increased to 110 ± 7 mmHg with 2 h of constriction, when renal arterial pressure had increased to 45 ± 2 mmHg.
ROLE OF THE KALLIKREIN‐KININ SYSTEM IN THE RENAL EFFECTS OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITION IN ANAESTHETIZED DOGS
Authors: Clappison B. H. , Anderson W. P. , Johnston C. I.
Published: June 2007

1. Administration of captopril (1.5mg/kg i.v.) to anaesthetized dogs was associated with an increase in renal blood flow of 56 ml min‐1 (s.e.m. = 13, n= 9) despite a significant fall of 17 mmHg (s.e.m. = 5, n= 9) in mean arterial pressure.

2. Treatment of dogs with the angiotensin receptor antagonist, Sar'lle8‐angiotensin II (2.5 fxgjkg per min i.v.), or the cyclo‐oxygenase inhibitor indo‐methacin (10 mg/kg i.v.) did not prevent the renal vasodilation and hypotension following angiotensin‐converting enzyme inhibition. This suggests that these effects are neither solely due to inhibition of the renin‐angiotensin system nor mediated by prostaglandins.

3. Increased urinary kinin excretion, possibly reflecting increased renal concentrations of kinins, accompanied the renal vasodilation after both captopril and renal artery occlusion.

4. The kallikrein‐kinin system may play a role in the regulation of the renal vasculature in anaesthetized dogs.
DIFFERING NORADRENALINE KINETICS IN ESSENTIAL HYPERTENSION AND DEPRESSIVE ILLNESS, TWO DISEASES IN WHICH THE PLASMA CONCENTRATION OF NORADRENALINE IS SOMETIMES ELEVATED
Authors: Esler M. , Turbott J. , Schwarz R. , Leonard P. , Jackman G. , Skews H. , Bobik A. , Jennings G. , Korner P.
Published: June 2007

1. The rate of spill‐over of noradrenaline to plasma, and neuronal noradrenaline uptake, which influences spill‐over, were studied in patients with essential hypertension and depressive illness.

2. Noradrenaline spill‐over was increased in seven of thirty‐four patients with essential hypertension and five of eleven patients with primary depressive illness, compared with values in seventeen normal subjects (range 1.0–3.63 nmol/min perm2).

3. Faulty neuronal reuptake of noradrenaline seemed to be the cause of higher noradrenaline spill‐over in patients with essential hypertension. Increased sympathetic nerve firing rates apparently were responsible in the primary depres‐sives, despite their normal blood pressure.

4. These puzzling findings suggest that hypertension occurs when neurotransmitter excess is due to defective noradrenaline reuptake (in essential hypertension), but not chronically increased nerve firing (in depressive illness).
THE EFFECTS OF INDOMETHACIN IN TREATED HYPERTENSIVE PATIENTS
Authors: Wing L. M. H. , Bune A. J. C. , Chalmers J. P. , Graham J. R. , West M. J.
Published: June 2007

1. Twelve treated hypertensive patients (ages 58–71 years) who had also been treated for joint disease participated in a randomized double‐blind crossover placebo‐controlled study to investigate the effects of indomethacin (25 mg three times daily) on blood pressure and biochemical parameters over a 6‐week period.

2. Blood pressure was increased in all patients throughout the indomethacin treatment period (P<0.001) ‐ average mean blood pressure increases were 9 mmHg (casual), 8 mmHg (supine), 10 mmHg (standing).

3. The blood pressure increase during indomethacin treatment was independent of the particular antihypertensive regimen in use.

4. Plasma aldosterone concentration was reduced by 50% (P<0.01), plasma renin activity was reduced by 43% (P= 0.102) and plasma urea concentration was increased by 17% (P<0.001) during indomethacin treatment.

5. The findings confirm that indomethacin impairs the blood pressure lowering effect of antihypertensive regimens.
EFFECTS OF MECLOFENAMATE AND CAPTOPRIL ON BLOOD FLOW TO THE KIDNEY AND SPLEEN IN CONSCIOUS RABBITS SUBJECTED TO MILD HAEMORRHAGE
Authors: Banks Richard A. , Beilin Lawrence J. , Soltys Jan , Davidson Lisa
Published: June 2007

1. Regional haemodynamic responses to mild haemorrhage were studied in three groups each of seven conscious rabbits, in the presence of either buffer, the prostaglandin cyclo‐oxygenase inhibitor meclofenamate, or the kininase II inhibitor captopril.

2. Renal and splenic vasoconstriction occurred with meclofenamate in haemorrhaged animals, and were accentuated by the subsequent administration of captopril.

3. Captopril alone caused mild renal vasodilatation, but subsequent administration of meclofenamate again caused vasoconstriction.

4. Flow to the adrenal coronary, cerebral and hepatic artery circulations was unaffected by meclofenamate or captopril after haemorrhage.

5. The results indicated that the enhanced vasopressor activity occurring during haemorrhage greatly increased the dependence on vasodilator prostaglandins of flow to the renal and splenic vascular beds.

6. The vasoconstrictor effect of meclofenamate does not appear to be due to unopposed action of angiotensin II when prostaglandin synthesis is suppressed.
CARDIOHAEMODYNAMIC EFFECTS OF LONG‐TERM INTRAVENOUS ADMINISTRATION OFW‐(2‐HYDROXYETHYL)NICOTINAMIDE NITRATE (SG‐75), A POTENT CORONARY VASODILATOR: COMPARISON WITH GLYCERYL TRINITRATE
Authors: Sakai K. , Shiraki Y. , Yamazaki T. , Akima M. , Nabata H. , Ohba Y.
Published: June 2007

1. Cardiohaemodynamic changes have been studied in beagle dogs treated with intravenous injections of either 300 μg/kg of N‐(2‐hydroxyethyl) nicotinamide nitrate (SG‐75) or 30 μg/kg of glyceryl trinitrate three times a day for 1 ‐2 months. Throughout the experimental period, no significant changes in general behaviour, body weights and plasma levels of enzymes and substrates were observed in either the SG‐75‐ or glyceryl‐trinitrate‐treated groups.

2. At 1 and 2 months after the start of chronic drug administrations, the dogs were anaesthetized and measurements were made of resting systemic blood pressure, pulse pressure, heart rate, right atrial pressure, coronary blood flow, aortic blood flow, left ventricular (LV) pressure and LVdP/dt: there were no significant differences between non‐treated dogs and dogs treated chronically with SG‐75 or glyceryl trinitrate.

3. The effects of the acute intravenous administration of SG‐75 and glyceryl trinitrate were examined in dogs pretreated intravenously with SG‐75 (300 μg/kg) and glyceryl trinitrate (30 μg/kg), respectively, three times a day for 1‐2 months. The depressor and coronary vasodilator responses to the two drugs remained unchanged in comparison with those in non‐treated dogs.

4. These results indicated that, with the doses used, neither SG‐75 nor glyceryl trinitrate produced changes in sensitivity or tolerance after long‐term intravenous administration.
THE EFFECT OF LONG‐TERM CHLORPROMAZINE AND DESIPRAMINE TREATMENT ON ADRENAL CORTICOSTERONE, CYCLIC AMP, AND CHOLESTEROL DISTRIBUTION IN RATS
Authors: Hung Francis , Chan Mo‐Yin
Published: June 2007

1.Male rats were injected intraperitoneally with chlorpromazine (10 mg/kg) and desipramine (10 mg/kg), respectively, twice daily for 2 weeks.

2. The adrenal corticosterone concentrations were significantly lowered in chlorpromazine‐ and desipramine‐treated rats.

3. Large dose of corticotrophin would increase the adrenal corticosterone level in chlorpromazine‐treated rats but the adrenal response was significantly less than in the untreated controls.

4. The adrenal cyclic AMP level was similar in treated and control rats and the adrenal response to corticotrophin was not decreased at the cyclic AMP level.

5. The cholesteryl ester concentrations in the adrenals were significantly increased by drug treatment, although the free cholesterol concentrations were unchanged in the cytosol and mitochondrial cell fractions.

6. The possible site of action of chlorpromazine in suppressing corticosterone production is discussed.
EFFECTS OF 2‐NICOTINAMIDOETHYL NITRATE (SG‐75) ON PANCREATIC SECRETION IN THE ISOLATED, BLOOD‐PERFUSED PANCREAS OF THE DOG
Authors: Iwatsuki K. , Ikeda K. , Chiba S.
Published: June 2007

1. The effects of 2‐nicotinamidoethyl nitrate (SG‐75) on the secretion of pancreatic juice were compared with those of acetylcholine, secretin and pancreozymin in the isolated, blood‐perfused dog pancreas.

2. Intra‐arterial administration of SG‐75 (0.3‐3 mg) elicited a dose‐dependent increase in pancreatic secretion. Acetylcholine (10‐100 μg), secretin (0.03‐0.3 units) and pancreozymin (0.1‐1.0 units) also elicited increased secretion.

3. Secretory responses to acetylcholine were inhibited by treatment with atropine, while SG‐75‐, secretin‐, and pancreozymin‐induced secretions were not modified.

4. Bicarbonate concentrations in pancreatic juice induced by SG‐75 and secretin were increased in a dose‐dependent manner. However, there were slight changes with acetylcholine or pancreozymin.

5. Amylase activity in pancreatic juice was increased by SG‐75, acetylcholine and pancreozymin, but was decreased by secretin.

6. These results suggest that SG‐75 stimulates pancreatic secretion by acting both on the acinar and ductular cells of the dog pancreas.
POTENTIATION OF THE NEGATIVE CHRONOTROPIC AND INOTROPIC EFFECTS OF ADENOSINE BY 2‐PHENYLAMINOADENOSINE
Authors: Chiba Shigetoshi , Watanabe Hidehiko
Published: June 2007

Effects of 2‐phenylaminoadenosine on SA nodal pacemaker activity and atrial contractility were studied, using eleven isolated, blood‐perfused dog atrial preparations. The compounds were administered via the cannulated sinus node artery of the isolated atrium.

2‐Phenylaminoadenosine induced negative chronotropic and inotropic effects and was 100 times less potent than adenosine in this action.

The interaction between adenosine and 2‐phenylaminoadenosine was studied. 2‐Phenylaminoadenosine potentiated the effect of adenosine on atrial muscle, but not that of acetylcholine.
THE EFFECT OF PHENTOLAMINE ON ACTIVE AND INACTIVE RENIN RELEASE IN HUMAN RENOVASCULAR HYPERTENSION
Authors: Pedrinelli R. , Arzilli F. , Sassano P. , Salvetti A.
Published: June 2007

1. Phentolamine was infused at low increasing doses (0.2, 0.3, 0.4 and 0.5 mg/min) in five patients with unilateral renal artery stenosis measuring active and inactive (cryoactivable) renin in the renal veins from the stenosed and nonstenosed kidney and in a peripheral vein.

2. PRA values from the stenosed kidney (11.59, s.e.m. = 5.79 pmol ang I/ml per h) were higher than those in the peripheral vein (5.19, s.e.m. =2.64) while these latter were similar to those from the contralateral kidney (5.09, s.e.m. =2.93). Phentolamine significantly increased PRA from the stenosed kidney and in the peripheral vein in a dose‐related manner. PRA changes were unrelated both to blood pressure decrements and to heart rate increments induced by the drug.

3. Before phentolamine, inactive renin from the stenosed kidney (5.19, s.e.m. = 2.84 pmol ang I/ml per h) did not differ significantly from that on the contralateral side (3.15, s.e.m. = 1.96) and in the peripheral vein (4.40, s.e.m. = 1.96). Phentolamine induced significant (P < 0.005) increments of inactive renin only from the stenosed kidney at the doses of 0.3, 0.4 and 0.5 mg/min. Inactive renin from the contralateral kidney was unchanged and it tended to increase, but not to a significant extent, in the peripheral vein. A highly significant relationship was found between active and inactive renin from the stenosed kidney (r = 0.79, P < 0.001, n= 25) and in peripheral blood (r = 0.71, P < 0.001, n= 25) but not from the stenosed kidney (r = 0.29, n= 25).

4. These results suggest that phentolamine, infused at low increasing doses causes an increase of PRA only in the stenosed kidney, an action which does not seem to be wholly explained by either sympathetic nervous system activation or decrease of renal perfusion pressure, and which suggests an action on intrarenal a‐adrenoreceptors. Furthermore, phentolamine stimulated inactive renin release only from the stenosed kidney without evidence of intrarenal conversion of the inactive into the active form.
THE EFFECT OF LONG TERM TREATMENT WITH A β‐ADRENOCEPTOR BLOCKER, l‐PROPRANOLOL, ON THE DISTRIBUTION OF CARDIAC OUTPUT OF THE LATE GESTATIONAL GUINEA‐PIG
Authors: Bjellin Leif , Mårtensson Lena
Published: June 2007

The effects of daily administration of propranolol on the distribution of cardiac output were studied in the late pregnant guinea‐pig.

The animals were given either saline, 5 or 50 mg/kg per day ofl‐propranolol for 15 days during the last trimester of gestation.

Blood flow responses were assessed by injecting 15 μm microspheres into the conscious animal one to two days prior to parturition.

The fraction of cardiac output reaching the placentas was significantly reduced in both groups (P<0.5 andP< 0.001, respectively), while flow to all other organs studied remained unaltered.

It is suggested that propranolol exerts a selective effect on the placental vascular bed in the guinea‐pig.
BLOOD PRESSURE AND ITS RELATIONSHIP TO LOW LEVELS OF ALCOHOL CONSUMPTION
Authors: Cooke Kenneth M. , Frost Gavin W. , Stokes Gordon S.
Published: June 2007

1. The association between average weekly alcohol consumption and blood pressure was studied in relation to age, adiposity and smoking in 13 535 men and 7385 women.

2. There was a progressive increase in blood pressure with increasing alcohol consumption, even at low levels of consumption.
VASCULAR SMOOTH MUSCLE SEROTONIN AND α‐ADRENOCEPTORS
Authors: Marwood John F. , Stokes Gordon S.
Published: June 2007

1. Rat isolated perfused tail arteries were used to investigate interactions between serotonin receptors and α‐adrenoceptors.

2. Ketanserin was shown to be a potent serotonin antagonist (pA2=9.17, s.e.m. =0.06, n= 6) which also antagonized phenylephrine {pA2= 7.47, s.e.m. =0.10, n= 4) and noradrenaline (pA2= 7.55, s.e.m. =0.14, n = 6).

3. Ketanserin reduced the maximal response to serotonin but not to phenylephrine or noradrenaline.

4. Prazosin antagonized phenylephrine (pA2= 9.60, s.e.m. =0.12, n= 5) and noradrenaline (pA2= 9.14, s.e.m.=0.11, n= 6) and had no effect on maximal responses. Prazosin reduced the maximal response to serotonin but did not displace the dose‐response curve.

5. These results are interpreted to indicate the existence of separate, but overlapping, serotonin and a‐adrenoceptors.
ERYTHROCYTE CATION FLUXES IN NORMAL AND HYPERTENSIVE HUMAN SUBJECTS
Authors: Stokes G. S. , Monaghan J. C. , Middleton A. T.
Published: June 2007

1. Intracellular cation concentrations ([Na]i, [K]i and influxes of 22Na and 86Rb were determined in the erythrocytes of hypertensive and control groups of subjects.

2. In both groups [Na]i showed a positive correlation with frusemide‐resistant Na influx and was inversely correlated with ouabain‐sensitive Rb influx, whereas [K]i was inversely correlated with frusemide‐sensitive Na influx (FSNal).

3. No significant differences between groups were found in [Na]i, [K]i or frusemide‐resistant Na influx.

4. FSNal was greater in males than females.

5. FSNal was slightly greater (P0.06) in the hypertensive group, but the significance of the difference diminished with sex‐matching.

6. Ouabain‐sensitive Rb influx was increased in the hypertensive group.