bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF HISTAMINE RECEPTOR ANTAGONISM ON ADRENALINE‐INDUCED CHANGES IN BLOOD PRESSURE IN INTACT DOGS
Authors: Johnson Michael D. , Williams J. Lynn
Published: June 2007

1. This study was designed to test the hypothesis that histamine may contribute to the vasodepressor response which occurs in response to physiologic increments in adrenaline concentration in intact animals. Accordingly, following a control period of 30 min, adrenaline was infused intravenously for 45 min at a rate of 250 ng/kg per min in 14 anaesthetized dogs (Group 1).

2. A second group of eight dogs received an identical adrenaline infusion following complete H1 and H2‐histamine receptor antagonism with tripelennamine plus cimetidine (Group II).

3. A time control group of experiments, in which no drugs were infused, as well as groups receiving adrenaline plus either tripelennamine or cimetidine, were also performed.

4. In Group I, adrenaline infusion increased heart rate and reduced mean arterial blood pressure by 10 mmHg (P <0.01).

5. Following combined H1 and H2‐histamine receptor antagonism (Group II), adrenaline infusion failed to reduce mean arterial blood pressure.

6. However, mean arterial blood pressure was reduced significantly in the groups receiving adrenaline plus only one of the histamine receptor blocking agents.

7. Since only the combined histamine receptor blockade completely eliminated the vasodepressor response to adrenaline, the data suggest that histamine may play a physiological role in the vasodepressor response to circulating adrenaline in the intact animal, and that both H1‐ and H2‐histamine receptors may be involved.
THE EFFECT OF THE 'HYPERTENSINOGENIC STEROID, 9α‐FLUORO‐CORTISOL ON BLOOD PRESSURE IN SHEEP WITH ACTH‐INDUCED HYPERTENSION
Authors: Mills Eric H. , Coghlan John P. , Denton Derek A. , Nelson Mark A. , Spence Campbell D. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. The effect of treatment with 9α‐fluorocortisol (9aFF), a steroid which causes hypertension in sheep, was examined in sheep with ACTH‐induced hypertension.

2. ACTH treatment alone increased mean arterial pressure (MAP), plasma Na concentration, water intake and urine volume and decreased plasma K concentration.

3. 9αFF treatment, for 3 days during continuing ACTH administration, did not change blood pressure but increased heart rate, water intake and urine volume and decreased urinary K excretion.

4. As 9αFF did not cause a further increment in blood pressure in sheep with ACTH‐induced hypertension it is possible that both ACTH and 9αFF may produce hypertension by similar mechanisms.
THE EFFECT OF ALTHESIN, KETAMINE OR PENTOTHAL ON RENAL FUNCTION IN SALINE LOADED RATS
Authors: Chen C. F. , Chapman B. J. , Munday K. A.
Published: June 2007

1. Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery.

2. A steady‐state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excretion rates, GFR, ERPF, ERBF and blood pressure were measured.

3. Five groups of rats were studied: (1) control animals given saline in place of any anaesthetic agent, all parameters measured remained constant; (2) althesin (1.2 mg/kg), all parameters remained constant except for the blood pressure which decreased slightly for 5 min; (3) althesin (12 mg/kg); (4) ketamine (50 mg/kg); (5) pentothal (50 mg/kg). The above anaesthetics altered all of the measured parameters except urine output.

4. Various mechanisms for these anaesthetic agents are discussed.

5. In althesin anaesthetized rats, all the retarded renal parameters recovered within 30 min. It is concluded that for the study of renal function, if a brief anaesthesia is needed, althesin is a more suitable anaesthetic agent.
EFFECTS OF OPIATES AND OPIOIDS ON INTRAOCULAR PRESSURE OF RABBITS AND HUMANS
Authors: Drago F. , Panissidi G. , Bellomio F. , Belle A. Dal , Aguglia E. , Gorgone G.
Published: June 2007

1. Acute intraocular injection of morphine or D‐Ala‐met‐enkephalinamide (D‐Ala‐E) in rabbits caused a sustained decrease in intraocular pressure. Conjunctival instillation of naloxone solution prevented the lowering effect of morphine or D‐Ala‐E on intraocular pressure.

2. Aqueous outflow facility appeared to be significantly higher in patients addicted to morphine or heroin than in healthy volunteers. Intraocular pressure was significantly lower in addicted patients than in control subjects. Conjunctival instillation of naloxone solution decreased aqueous outflow facility and increased intraocular pressure in addicted patients.

3. Patients with chronic open angle glaucoma showed a significant decrease in intraocular pressure after conjunctival instillation of morphine solution.

4. It is concluded that intraocular opiate receptors are involved in the regulation of intraocular pressure in animals and humans.
USE OF SYNTHETIC OLIGONUCLEOTIDE AND RECOMBINANT DNA PROBES TO STUDY RENIN GENE EXPRESSION
Authors: Darby Ian A. , Aldred G. Peter , Coghlan John P. , Fernley Ross T. , Penschow Jennifer D. , Ryan Graeme B.
Published: June 2007

1. Using hybridization histochemistry renin gene expression has been localized in the juxtaglomerular apparatus (JGA) of the renal cortex in both mouse and sheep kidney.

2. This technique also located renin gene expression in afferent arterioles and interlobular arteries distant from the glomerular tuft in lamb renal cortex.

3. A short (30 mer) synthetic oligonucleotide probe, complementary to a region of the mouse submaxillary gland renin gene, specifically labelled mouse submaxillary gland and kidney.

4. Hybridization histochemistry and Northern blot analysis using both the synthetic oligonucleotide (mouse) probe and a 700 base pair recombinant (sheep) probe showed differences in renin gene expression in the kidney in response to Na restriction in the mouse and Na depletion in the sheep.
BLOOD PRESSURE, SALT TASTE AND SODIUM EXCRETION IN RATS EXPOSED PRENATALLY TO HIGH SALT DIET
Authors: Myers J. B. , Smidt V. J. , Doig S. , Nicolantonio R. Di , Morgan T. O.
Published: June 2007

1. Blood pressure, sodium excretion and salt taste were examined in Sprague Dawley (SD) and Munich Wistar (MW) rats exposed prenatally to either a high salt (2.3% NaCl w/w) or control diet.

2. There was no significant difference in blood pressure at 2, 6 or 12 months between high salt and control groups in either strain. Similarly there was no significant difference in sodium excretion following a saline load by gavage (150 mmol/l, 1.5% BW).

3. Munich Wistar rats which received high salt diet prenatally exhibited a reduced saline preference when offered a choice between water and 150 mmol/l NaCl as drinking fluid. There was no significant difference in saline preference between Sprague Dawley rats which received the high salt or control diet.

4. Prenatal exposure to high salt diet failed to alter the blood pressure or excretion of a salt load in either SD or MW rats. In MW rats but not SD high salt diet prenatally resulted in a reduced saline preference at 3 months of age.
TIME COURSE OF CHANGES IN BLOOD PRESSURE, ALDOSTERONE AND BODY FLUIDS DURING ENALAPRIL TREATMENT: A DOUBLE‐BLIND RANDOMIZED STUDY VS HYDROCHLOROTHIAZIDE PLUS PROPRANOLOL IN ESSENTIAL HYPERTENSION
Authors: Semplicini A. , Rossi G. P. , Bongiovì S. , Perissinotto F. , Samà B. , Mozzato M. G. , Pessina A. C.
Published: June 2007

1. Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive.

2. The effects of the angiotensin converting enzyme inhibitor enalapril (10‐40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80‐160 mg/day, p.o.) for 4 more weeks during a randomized double‐blind parallel study in 14 essential hypertensives.

3. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids.

4. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P < 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values.

5. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal.

6. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.
THE RELATIONSHIP BETWEEN TISSUE LEVELS OF CYCLIC GMP AND TRACHEAL SMOOTH MUSCLE RELAXATION IN THE GUINEA‐PIG
Authors: Suzuki Kiyoshi , Takagi Kenzo , Satake Tatsuo , Sugiyama Satoru , Ozawa Takayuki
Published: June 2007

1. The effect of cyclic GMP was investigated using guinea‐pig tracheal smooth muscle.

2. 8‐Bromo‐cyclic GMP showed a dose‐dependent relaxation of spontaneous tension of tracheal smooth muscle.

3. Administration of sodium nitroprusside induced dose‐dependent relaxation of tracheal smooth muscle as well as an increase in tissue levels of cyclic GMP.

4. Nicorandil, N‐(2‐hydroxyethyl) nicotinamide nitrate showed dose‐dependent relaxation of tracheal smooth muscle and an increase in cyclic GMP levels in the tissue.

5. N‐(2‐aminoethyl) nicotinamide dihydrochloride, which is a nicorandil derivative and differs minimally in its molecular structure (‐NH2 vs ‐NO2), had neither a relaxant effect on tracheal smooth muscle nor did it increase the level of cyclic GMP in the tissue.

6. The rise in cyclic GMP levels preceded the relaxation of tracheal smooth muscle induced by sodium nitroprusside.

7. These results suggest that cyclic GMP is one of the relaxant factors and that nitro‐derivatives exhibit their relaxant effect on the smooth muscle mediated by an increase in cyclic GMP level.
AROMATIC l‐AMINO ACID DECARBOXYLASE: HISTOCHEMICAL LOCALIZATION IN RAT KIDNEY AND LACK OF EFFECT OF DIETARY POTASSIUM OR SODIUM LOADING ON ENZYME DISTRIBUTION
Authors: Adam William R. , Culvenor Anne J. , Hall John , Jarrott Bevyn , Wellard R. Mark
Published: June 2007

1. Utilizing a mono‐specific antiserum produced in rabbits to hog kidney aromatic l‐amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining.

2. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts.

3. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney.

4. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading.

5. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium loading.
SAR1‐LEU8‐ANGIOTENSIN II REVERSES THE EFFECTS OF CAPTOPRIL ON RENAL FUNCTION IN RATS
Authors: Harris P. J. , Mitchell K. D. , Munro J. O.
Published: June 2007

1. In Inactin‐anaesthetized rats inhibition of angiotensin converting enzyme by captopril resulted in a small decrease in mean arterial blood pressure accompanied by increases in the rates of glomerular filtration, water and electrolyte excretion.

2. Infusion (100 pmol/min) of sar1‐leu8‐angiotensin II (sar1‐leu8‐AII) during continuing converting enzyme blockade reversed these changes in renal function but had no effect on arterial blood pressure.

3. The data indicate that sar1‐leu8‐AII has partial agonist activity in the kidney although it acts as an antagonist of AII in the systemic circulation. This supports the proposai that angiotensin receptors within the kidney differ from those in the peripheral circulation.
DISTRIBUTION AND KINETICS OF INJECTED NICKEL IN THE PREGNANT RAT
Authors: Mas A. , Peligero M. J. , Arola LI. , Alemany M.
Published: June 2007

1. Radioactive nickel (Ni) was injected intraperitoneally both carrier‐free and in 4 mg/kg body weight of Ni as NiCl2 doses in control and pregnant rats on days 12 and 19 after impregnation.

2. The time‐course of disappearance of radioactivity from the tissues and blood of the rat was determined, as well as the degree of incorporation of radioactivity from the injected doses.

3. The maximal uptake of the metal 15 min after injection corresponded to kidney uptake, followed by pancreas, blood plasma and then all other target organs studied. The presence of cold nickel resulted in higher uptake of the metal without much change in the proportion of distribution between tissues. The kinetics of disappearance was similar in all tissues and was little affected by pregnancy, with mean half‐lives of about 3‐5 h irrespective of doses.
NATRIURETIC AND HYPOTENSIVE EFFECTS OF α‐HUMAN ATRIAL NATRIURETIC POLYPEPTIDE IN ANAESTHETIZED DOCA‐SALT HYPERTENSIVE RATS
Authors: Kondo K. , Kida O. , Kangawa K. , Matsuo H. , Tanaka K.
Published: June 2007

1. Both natriuretic and hyportensive effects of α‐human atrial natriuretic polypeptide (α‐hANP) were investigated in anaesthetized DOCA‐salt hypertensive rats and control rats.

2. An intravenous injection of two doses (0.3 and 3.0 μg/kg body weight) of α‐hANP produced a rapid and marked increase in natriuresis and fall in blood pressure in DOCA‐salt rats.

3. Natriuretic and hypotensive effects of α‐hANP in DOCA‐salt rats were significantly greater than those in the control rats.

4. It is suggested that DOCA‐salt rats may have an enhanced natriuretic and hypotensive responsiveness to α‐hANP.
DICLOFENAC SODIUM IN THE TREATMENT OF PRIMARY NOCTURNAL ENURESIS: DOUBLE‐BLIND CROSSOVER STUDY
Authors: AL‐Waili Noori S.
Published: June 2007

1. The prostaglandin synthesis inhibitor diclofenac sodium has been compared with a placebo in the treatment of primary nocturnal enuresis in a double‐blind crossover trial.

2. Twenty patients were entered: 14 female, six male; age range 6–17 years.

3. The results showed that diclofenac sodium was significantly more effective than placebo in the treatment of nocturnal enuresis.
NO EFFECT OF ATRIAL NATRIURETIC FACTOR ON CARDIAC RATE, FORCE AND TRANSMITTER RELEASE
Authors: Hiwatari Masao , Satoh Keisuke , Angus James A. , Johnstond̊ Colin I.
Published: June 2007

1. The effects of atrial natriuretic factor (ANF, 1‐300 nmol/l) on cardiac rate, force and neurotransmitter release were examined in guinea‐pig isolated heart preparations.

2. Synthetic ANF had little effect on the contractile force of electrically driven papillary muscle regardless of the presence or absence of isoprenaline.

3. The pulse period of spontaneously beating right atria was not affected by ANF. Neither the positive nor negative chronotropic effect of isoprenaline or bethanechol respectively were changed in the presence of ANF.

4. ANF did not affect the release of neurotransmitter from the nerve endings in the isolated atrium.

5. ANF was confirmed to relax isolated aortic rings precontracted with either noradrenaline (ANF, IC50= 3 nmol/l, s.e.m. = 0.2, n= 5) or potassium (ANF, IC50= 24 nmol/l, s.e.m. = 0.2, n= 5).

6. These results demonstrate that ANF within doses effective for vasorelaxation has no appreciable effect on myocardial function or neutrotransmitter release in the heart.
PROSTAGLANDIN SYNTHETASE INHIBITION WITH INDOMETHACIN RECTAL SUPPOSITORIES IN THE TREATMENT OF ACUTE AND CHRONIC URINARY CALCULUS OBSTRUCTION
Authors: AL‐Waili Noori S.
Published: June 2007

1. The effect of indomethacin suppositories on both acute urinary colic and urinary calculus, resistant or refractory to conventional therapy with analgesics and spasmolytics was investigated.

2. Fifty‐five patients with acute urinary colic refractory to treatment with repeated injections of antispasmodics and analgesics had dramatic or complete pain relief after receiving indomethacin suppositories (100 mg) (P<0.01). Fifteen of the 55 patients passed urinary stones within 30 days of treatment with indomethacin. Three out of 30 other patients with renal or ureteric stones were treated with indomethacin suppositories (100 mg) twice daily. Twenty‐one of the 30 patients passed their stones within 30 days of treatment.

4. It is concluded that indomethacin suppositories can relieve acute urinary colic resistant to treatment with analgesic/antispasmodic drugs, and facilitate expulsion of urinary calculi.

5. The mechanism of action of indomethacin is discussed in terms of its analgesic and anti‐inflammatory effects and its prostaglandin synthesis inhibition.
ADRENOCORTICOID‐DEPENDENT α‐LACTALBUMIN SYNTHESIS IN RAT MAMMARY GLAND EXPLANTS: ANTAGONIST STUDIES
Authors: Quirk Susan J. , Gannell Jennifer E. , Funder John W.
Published: June 2007

1. Though adrenal steroids are required for the production of α‐lactalbumin by mammary gland explants, the physiological class of steroid activity (mineralocorticoid, glucocorticoid) remains to be established.

2. α‐Lactalbumin production by mammary gland explants from mid‐pregnant rats has been shown in previous studies to be increased by high doses of aldosterone, but not by deoxycorticosterone; in six of 11 experiments corticosterone, the physiological glucocorticoid in the rat, elevated α‐lactalbumin; in five other studies corticosterone had no effect.

3. In the present studies the mineralocorticoid antagonist, spirolactone, at very high doses (3‐10 μmol/1) blocked the stimulatory effect on α‐lactalbumin levels of both 30 nmol/1 corticosterone and 3 nmol/1 RU 26988, a pure synthetic glucocorticoid (Type II) receptor agonist.

4. Receptor studies, however, indicated that this antagonism is consistent with Type II, glucocorticoid receptor occupancy by spirolactone.

5. Since deoxycorticosterone is without agonist effect, and only very high doses of spirolactone affect α‐lactalbumin synthesis, we conclude that the effect of adrenal steroids on α‐lactalbumin production is a manifestation of glucocorticoid and not mineralocorticoid activity.
EFFECTS OF ENDOTHELIUM‐DERIVED RELAXING FACTOR ON THE SMOOTH MUSCLE OF THE RAT TAIL ARTERY
Authors: Kotecha N. , Neild T. O.
Published: June 2007

1. Simultaneous measurements of smooth muscle membrane potential and tension were made from isolated pieces of rat tail artery.

2. A single electrical stimulus to the perivascular nerves produced a transient contraction of the smooth muscle. The amplitude of the contraction was increased after removal of the endothelium.

3. The excitatory junction potentials and action potentials in the smooth muscle had the same amplitudes before and after removal of the endothelium.

4. Tension obtained by direct stimulation of the arterial muscle in guanethidine‐treated arteries was also increased by removal of the endothelium.

5. When the artery was constricted by noradrenaline or 5‐hydroxytryptamine, electrical stimulation caused a relaxation that was reduced by removing the endothelium.

6. It was concluded that the electrical stimulus released the endothelium‐derived relaxing factor (EDRF) which reduced the amount of contractile force that could be produced by an action potential in the smooth muscle.
EFFECT OF SODIUM INTAKE AND SODIUM DELIVERY TO THE MACULA DENSA ON RENAL RENIN CONTENT AND JUXTAGLOMERULAR APPARATUS MORPHOLOGY
Authors: Wong T. , Morgan T. O. , Alcorn D. , Ryan G. B.
Published: June 2007

1. Active and inactive renin were measured in individual juxtaglomerular apparatus (JGA) and in whole kidney homogenates.

2. The morphology of the JGA was examined in microbiopsy glomerular specimens and in kidneys fixed by arterial perfusion.

3. In rats on high and normal salt intake the total renin content of a single JGA was 14 (s.e.m. = 3) and 29 (s.e.m. = 4) ng AI/h, respectively. The amount of cystoplasm occupied by renin granules was 20% and 27%. Crystalline cores were seen in 1.5% and 7% of the granules, respectively.

4. Increased delivery of NaCl to the macula densa did not alter total renin, but decreased inactive renin from 30% to 0, crystalline core‐containing cells from 33% to 14% and decreased the percentage of granules with crystalline cores from 12% to 2.2%.

5. Increased sodium in the diet and increased delivery of NaCl to the macula densa decreased the proportion of renin present in the inactive form and decreased the proportion of crystalline cores.

6. These coincidental alterations suggest that crystalline cores contain inactive renin and suggest that the delivery of sodium to the macula densa activates renin.
EFFECTS OF TETRADECAPEPTIDE RENIN SUBSTRATE ON ISOLATED PREPARATIONS OF RAT CAUDAL ARTERY, GUINEA‐PIG ATRIA AND ON PITHED RAT BLOOD PRESSURE
Authors: Ziogas J. , Story D. F. , Rand M. J.
Published: June 2007

1. In rat isolated caudal artery preparations, tetradecapeptide renin substrate enhanced the responses to sympathetic nerve stimulation (0.5 Hz, 10 s).

2. In guinea‐pig isolated atria, previously incubated in 3H‐noradrenaline, tetradecapeptide renin substrate enhanced the stimulation‐induced efflux of radioactivity.

3. The facilitation of noradrenergic transmission in rat caudal arteries and guinea‐pig atria was blocked by the angiotensin II receptor antagonist saralasin, but was not altered by converting enzyme inhibitors.

4. In the pithed rat tetradecapeptide renin substrate increased blood pressure and this effect was reduced by the converting enzyme inhibitor, captopril.
MODULATION OF PROXIMAL TUBULAR REABSORPTION BY ANGIOTENSIN II
Authors: Zhuo J. , Harris P. J. , Skinner S. L.
Published: June 2007

1. In shrinking‐drop micropuncture studies in anaesthetized rats proximal tubular fluid reabsorption (Jva) decreased by 36% following intravenous infusion of enalapril. In a separate group of rats enalapril reduced fractional lithium clearance indicating decreased proximal fluid reabsorption.

2. Following enalapril, GFR rose by 46% but absolute proximal reabsorption rose by 22% indicating 48% effectiveness of proximal glomerulo‐tubular balance (GTB). Since renal blood flow and glomerular filtration rate (GFR) increased in parallel and arterial pressure fell, fluid uptake and proximal GTB were unlikely to have been decreased by peritubular physical forces.

3. In anaesthetized rats proximal fluid reabsorption and proximal GTB are modulated by endogenous All through direct stimulation of proximal tubular transport.
EFFECTS OF SHORT‐TERM MODIFICATION OF DIETARY SODIUM INTAKE ON PLASMA CATECHOLAMINES AND BLOOD PRESSURE IN PREHYPERTENSIVE CHILDREN
Authors: Howe P. R. C. , Rogers P. F. , Smith R. M. , Jureidini K. F.
Published: June 2007

1. The influence of dietary sodium intake on plasma catecholamines was examined as part of a dietary intervention study in 21 prehypertensive school children.

2. Diastolic blood pressure was significantly elevated in girls after 3 weeks on a high sodium diet compared with a low sodium diet. Plasma adrenaline levels were raised slightly by the high sodium intake but plasma noradrenaline was significantly reduced.

3. Increases of plasma catecholamines in response to standing or cold stress were unaffected by changes in sodium intake.

4. The results indicate that the pressor effect of dietary sodium in children is not attributable to increased sympathetic nerve activity.
PRESERVATION OF RENAL FUNCTION IN THE RAT REMNANT KIDNEY MODEL OF CHRONIC RENAL FAILURE BY BLOOD PRESSURE REDUCTION
Authors: Jackson B. , Debrevi L. , Cubela R. , Whitty M. , Johnston C. I.
Published: June 2007

1. The remnant kidney model of chronic renal failure was established in female Sprague‐Dawley rats subjected to surgical removal of the right kidney and segmentai infarction of seven‐eighths of the left kidney. Plasma creatinine (μmol/1) rose from 65 (s.e.m. = 16, n= 18) to 153 (s.e.m. = 27, t‐test, P < 0.001, d.f. = 17) over 6 weeks. Histological glomerulosclerotic lesions were present from 2 weeks and prominent by 6 weeks post‐surgery.

2. Rats were treated with enalapril (5 mg/kg per day, n= 11) or felodipine (30 mg/kg per day, n= 13) from 1 week post‐surgery, and their course compared to untreated rats (n= 18).

3. Blood pressure (mmHg) was lowered by both treatments. Six weeks post‐nephrectomy, systolic blood pressure in the untreated group was 176 (s.e.m. = 7, n= 18), enalapril group 122 (s.e.m. = 5, t‐test, P < 0.001, d.f. = 27), and felodipine group 128 (s.e.m. = 3, t‐test, P < 0.001, d.f. = 29).

4. Plasma creatinine (μmol/1) was lower in the enalapril group (110, s.e.m. = 8, t‐test, P < 0.05, d.f. = 27) but not the felodipine group (173, s.e.m. = 19, t‐test, n.s.) 6 weeks after subtotal nephrectomy compared to the untreated group (153, s.e.m. = 27).

5. Glomerulosclerosis (blinded histological score) was reduced with enalapril treatment (1.93, s.e.m. = 0.03, t‐test, P < 0.05, d.f. = 27) but not felodipine treatment (2.15, s.e.m. = 0.04, c.f. untreated 2.36, s.e.m. = 0.12, t‐test, n.s.). Urinary protein excretion (mg/24 h) was 84 (s.e.m. = 22, n= 13) in untreated rats, 15 (s.e.m. = 3, t‐test, t‐test, P < 0.001, d.f. = 22) in enalapril‐treated rats and 221 (s.e.m. = 35, n= 10) with felodipine treatment.

6. Functional and structural damage in the rat remnant kidney model of chronic renal failure was ameliorated by treatment with enalapril but not by treatment with felodipine.
THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA WITH NORMAL GFR. A UNIQUE PATHOPHYSIOLOGICAL MECHANISM FOR HYPERTENSION?
Authors: Gordon Richard D.
Published: June 2007

1. Based on 28 reported patients, constant features of the syndrome of hypertension and hyperkalaemia are hyperkalaemia, hyperchloraemia, normal renal glomerular function and, in all adult patients, hypertension.

2. Inconstant features include short stature, intellectual impairment and muscle weakness.

3. Levels of renin and aldosterone are low, but respond to dietary salt restriction and diuretic therapy, both of which reverse the hypertension and hyperkalaemia.

4. The basic abnormality is excessive renal sodium retention, leading to chronic suppression of renin and aldosterone; the latter is then hyporesponsive to the hyperkalaemic stimulus.

5. Dietary salt loading or impaired production of any natriuretic or chloriuretic factor (for example atrial natriuretic peptide or renal natriuretic prostaglandins) would predispose to development of the syndrome. With normal GFR, this appears to be a unique mechanism for hypertension and hyperkalaemia.
STIMULATION OF PHOSPHATIDYLINOSITOL METABOLISM IN THE HEART
Authors: Leung E. , Johnston C. I. , Woodcock E. A.
Published: June 2007

1. Receptor‐stimulated hydrolysis of inositol phospholipids was studied in atrial and ventricular myocytes isolated from guinea‐pigs.

2. Acetylcholine and carbachol stimulated inositol phosphate accumulation with a maximum of more than 12 times the unstimulated values in atrial myocytes and 7 times in ventricular myocytes.

3. The vasoactive peptides angiotensin II and vasopressin also stimulated inositol phosphate accumulation, but the maximum effect was lower than that mediated through muscarinic receptors.

4. However, the adenosine analogues, l‐N6‐phenylisopropyladenosine and 5'N‐ethylcarboxamidoadenosine which, like muscarinic agonists depress cardiac contractility, did not affect inositol phosphate accumulation at concentrations up to 10−4 mol/1.

5. Stimulation of phosphatidylinositol turnover in heart bears no obvious relationship to either contractility or release of atrial natriuretic factor.
EVOLUTION OF RENIN
Authors: Morris B. J. , Catanzaro D. F.
Published: June 2007

1. New gene data for three aspartyl proteases (human renin, mouse renin and human pepsin) permitted closer analysis of the gene duplication and fusion hypothesis for the evolution of this family of enzymes.

2. Alignment of sequences in the hemilobes of human pepsin revealed only weak homology in amino acid sequences. Nucleotides were, however, more homologous.

3. Splice junctions between putative duplicated exons did not match.

4. Repeated sequences in the human renin gene were detected by hybridization with total human DNA labelled with 32P. These were not, however, consistent with unequal crossing‐over between repeated sequences of an ancestral gene having occurred.

5. The data thus provide no immediate support for the gene duplication and fusion hypothesis. The symmetry in structure of an aspartyl protease may arise from the tendency of hydrophilic amino acids to be encoded at splice junctions. This would divide a molecule comprised mainly of β‐sheets into roughly superimposable domains.
FACTORS INFLUENCING THE EFFECTS OF INTRAVENOUS NALOXONE ON ARTERIAL PRESSURE AND HEART RATE AFTER HAEMORRHAGE IN CONSCIOUS RABBITS
Authors: Rutter Peter C. , Potocnik Simon J. , Ludbrook John
Published: June 2007

1. The circulatory responses to different intravenous doses of naloxone were studied in conscious rabbits before and after haemorrhage, under different conditions including prior ganglion blockade.

2. Unless there had been blood loss, naloxone elicited no pressor response, even in high dose. After bleeding so that arterial pressure fell to 40 mmHg, the dose‐response relationship for naloxone had two components. Over a low‐dose range (threshold 0.3 mg/kg) naloxone had a modest pressor effect but did not affect heart rate. Over a much higher dose range (threshold 0.6 mg/kg) naloxone caused a marked rise in arterial pressure and a profound bradycardia. The highest dose of naloxone examined (25 mg/kg) caused a rise in arterial pressure of 70 mmHg and a reduction in heart rate of 160 beats/min.

3. The pressor and bradycardic effects of naloxone were the same whether post‐haemorrhagic hypotension lasted 5, 10, 20 or 30 min.

4. The responses to naloxone in low or high dose depended much more closely on the volume of blood removed than on the level to which arterial pressure fell. Even after non‐hypotensive haemorrhage a high dose of naloxone had marked pressor and bradycardic effects.

5. Ganglion blockade prior to haemorrhage abolished the pressor response to a low, but not to a high, dose of naloxone.

6. It was concluded that prolonged and severe hypotension are not necessary to ‘prime’ the cardiovascular system to respond to naloxone after haemorrhage. In a high dose its pressor effects appear to be mediated post‐ganglionically, but in a low dose it may act within the central nervous system.
FURTHER EVIDENCE OF THE ROLE OF CYCLIC AMP AS A MEDIATOR OF THE DEPRESSANT EFFECTS OF β‐ADRENOCEPTOR AGONISTS AND PHOSPHODIESTERASE INHIBITORS ON SLOW‐CONTRACTING MAMMALIAN SKELETAL MUSCLES
Authors: Merican Zainuddin , Morat Paden , Dan Rahim , Khalid B. A. K.
Published: June 2007

1. The depressant effects of β‐adrenoceptor agonists and phosphodiesterase inhibitors on contractions of slow‐contracting mammalian skeletal muscles are associated with increased muscular cyclic AMP levels.

2. A strong correlation was found to exist between the percentage depression of contraction and the percentage increase in cyclic AMP level, irrespective of the drug used and regardless of the mechanism of cyclic AMP production.

3. The results strongly support the mediatory role of cyclic AMP in the depressant effects of β‐adrenoceptor agonists and phosphodiesterase inhibitors on slow‐contracting mammalian skeletal muscle contractions.
BRAIN NORADRENALINE AND THE DEVELOPMENT OF HYPERTENSION: THE EFFECT OF TREATMENT WITH CENTRAL 6‐HYDROXYDOPAMINE OR DSP‐4
Authors: van den Buuse Maarten , Versteeq Dirk H. G. , de Jong Wybren
Published: June 2007

1. The relative role of brain catecholamines in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied.

2. Treatments consisted in five weeks old SHR of central injections of 6‐hydroxydopamine (6‐OHDA), 3 × 200 μg either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), or of intraperitoneal (i.p.) injections of DSP‐4, either once or three times 50 mg/kg.

3. Compared to the pronounced attenuation of the development of hypertension following i.c.v. 6‐OHDA treatment, the i.c. 6‐OHDA treatment and the multiple DSP‐4 treatment were less effective. A single injection of DSP‐4 had only minor effects on blood pressure. Heart rate was markedly lower in i.c.v. 6‐OHDA treated SHR, but the other treatments induced no effects on this parameter.

4. Noradrenaline depletion was found in various parts of the brain particularly after i.c.v. 6‐OHDA or either DSP‐4 treatment. Brain dopamine and adrenaline were depleted to a lesser extent. However, the best correlation between blood pressure and brain catecholamine concentration was found for dopamine in the hippocampus and hypothalamus and for adrenaline in the hypothalamus. Noradrenaline levels were also correlated with blood pressure, but to a lesser extent.

5. These results suggest that the depletion of dopamine or adrenaline in the brain may be of more importance in the effects of neurotoxic treatments on the development of hypertension than the effects on brain noradrenaline. Thus, these experiments lend support to the hypothesis that brain noradrenaline systems may not play an important role in the development of hypertension in the SHR.
RELATION OF INTRAMYOCARDIAL PRESSURE TO CORONARY PRESSURE AT ZERO FLOW
Authors: Sabbah Hani N. , Marzilli Mario , Liu Zhi‐quan , Stein Paul D.
Published: June 2007

1. The purpose of this study was to determine the extent to which coronary pressure at zero coronary flow (Pf=0) may relate to extravascular compressive forces determined by direct measurements of left ventricular intramyocardial pressure.

2. Studies were performed in nine open‐chest anaesthetized dogs in which the anterior descending coronary artery was cannulated and perfused from the carotid artery. Coronary pressure was measured at the tip of the cannula.

3. Intramyocardial pressure was measured with a 1 mm diameter micromanometer inserted directly into the subepicardium. The atrioventricular node was obliterated by cautery and the heart was electrically paced. Long diastolic pauses, sufficient to allow coronary flow to reach zero, were produced by the cessation of electrical pacing.

4. In the autoregulated coronary bed, Pf=0, 47 mmHg (s.e.m. = 9), exceeded subepicardial pressure at zero flow, 23 mmHg (s.e.m. =2; P < 0.001). During maximal vasodilatation with adenosine, Pf=0, 16 mmHg (s.e.m. = 11), was not significantly different from subepicardial pressure at zero flow, 21 mmHg (s.e.m. =4). These observations indicate that, in addition to coronary vasomotor tone, diastolic myocardial tissue pressure is important in the genesis of Pf=0.
EFFECTS OF A SYNTHESIZED PHOSPHODIESTERASE INHIBITOR, ZSY‐27, ON PANCREATIC EXOCRINE SECRETION OF THE DOG
Authors: Iwatsuki K. , Yamagishi F. , Chiba S.
Published: June 2007

1. The effects of a synthesized phosphodiesterase inhibitor, ZSY‐27, on the secretion of pancreatic juice were investigated in dog isolated and blood‐perfused pancreas, and compared with those of secretin and dopamine.

2. Intravenous administration of ZSY‐27 (0.3‐1 mg/kg) elicited increases in pancreatic secretion. Intra‐arterial (i.a.) administration of ZSY‐27 (0.1‐1 mg) also elicited increased secretion. The secretory activity of ZSY‐27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 μg of dopamine.

3. The concentration of bicarbonate in the pancreatic juice induced by ZSY‐27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine.

4. ZSY‐27‐induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine.

5. Secretin‐induced secretion was significantly potentiated by infusion of ZSY‐27 (25 μg/min) but dopamine‐induced one was not.

6. These results suggest that ZSY‐27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intra‐cellular cyclic AMP concentration by inhibiting phosphodiesterase activity.
BAROREFLEX SENSITIVITY ALTERATION FOLLOWING TRANSIENT HEMISPHERIC ISCHAEMIA IN RATS: PROTECTIVE EFFECT OF ALPHAMETHYLDOPA AND GUANFACINE
Authors: Saad Mohamed A. A. , Elghozi Jean‐Luc , Meyer Philippe
Published: June 2007

1. The reflex tachycardia to arterial vasodilation was analysed in anaesthetized and ventilated Long Evans rats. Nicardipine was given by slow intravenous injection. The decrease in blood pressure was accompanied by a sympathetically mediated reflex tachycardia. The slope of the mean blood pressure‐pulse period relationship was considered as an index of baroreflex sensitivity. Two injections of nicardipine were given during a single experiment.

2. For studying the suprapontine control of the baroreflex arc, rats were subjected to transient (10 min) bilateral hemispheric ischaemia. These rats exhibited a blood pressure drop following recirculation and baroreflex sensitivity was impaired.

3. Pretreatment with α‐methyldopa, guanfacine and enalapril lowered mean blood pressure to a similar extent. In those rats pretreated with α‐methyldopa and guanfacine transient hemispheric ischaemia did not alter baroreflex sensitivity while enalapril pretreated rats exhibited an impaired baroreflex. The protective effect of α‐methyldopa and guanfacine against the cardiovascular consequence of hemispheric ischaemia may depend on reduced monoamine turnover resulting from central α‐adrenoceptor stimulation.
PRESSOR SENSITIVITY TO ANGIOTENSIN I AND ANGIOTENSIN II DURING THE DEVELOPMENT OF EXPERIMENTAL RENAL HYPERTENSION IN THE RAT
Authors: Doyle A. E. , Harrap S. B. , Torresi J.
Published: June 2007

1. Treatment with the potent angiotensin converting enzyme inhibitor perindopril completely prevented any rise in blood pressure in the 2‐kidney, 1 ‐clip (2K1C) model of renal hypertension in rats. Withdrawal of this inhibitor was followed by a slow rise in blood pressure.

2. In 2K1C rats treated with perindopril, pressor responses to angiotensin I fell during the treatment period, but returned to normal after the inhibitor was stopped. Pressor responses to angiotensin II (AII) increased during treatment with perindopril; this was presumably due to increased receptor sensitivity consequent on the falls in endogenous AII levels. Responses to AII fell to control levels after the inhibitor was stopped.

3. It is concluded that an increased pressor sensitivity to AII is not the cause of the slowly developing hypertension in the 2K1C model of hypertension, and that the slow pressor response to AII must be due to other factors.
RENAL PROSTAGLANDIN EFFLUX INDUCED BY VASOPRESSIN, DDAVP AND ARACHIDONIC ACID: CONTRASTING PROFILE AND SITES OF RELEASE
Authors: Miller Mark J. S. , Westlin William F. , McNeill Helen , McGiff John C.
Published: June 2007

1. Prostaglandin (PG) efflux into ureteral (UE) and venous effluents (VE) of rabbit isolated perfused kidneys was determined by superfusion bioassay and radioimmunoassay (RIA), in response to injections of arginine‐vasopressin (AVP), the non‐pressor vasopressin analogue 1‐deamino‐8‐D‐arginine vasopressin (dDAVP) and arachidonic acid (AA).

2. dDAVP (10–1000 ng) failed to stimulate renal PG release, whereas AVP (10–100 ng) and AA (10–50 μg) caused a dose‐dependent release of PG.

3. AVP evoked PG release into both effluents with release into the VE greater than UE at high doses. In contrast, PG release by AA was almost exclusively into the VE.

4. Indomethacin (2.8 × 10‐6 mol/1) abolished AVP‐ and AA‐induced PG efflux in both effluents, and vasodepressor responses to AA.

5. PGE2 was the predominant PG released in response to AVP in both effluents whereas AA released primarily 6‐keto‐PGF1α.

6. The contrasting sites and profile of released PG suggest that exogenous AA and AVP stimulate the release of PG from different regions/cell types within the kidney.
PROSTANOID CONCENTRATIONS IN HUMAN CSF FOLLOWING ACUTE ISCHAEMIC BRAIN INFARCTION
Authors: Fagan S. C. , Castellani D. , Gengo F. M.
Published: June 2007

1. Thromboxane A2 and prostacyclin are two compounds which have been implicated as important modulators of local cerebral blood flow.

2. Concentrations of the stable metabolites of these two compounds, thromboxane B2 and 6‐keto‐PGF1α, were measured in cerebrospinal fluid (CSF) from eight acute ischaemic stroke patients and 14 patients with no evidence of cerebrovascular disease.

3. Concentrations of thromboxane B2 ranged from 0.15 to 4.0 pg/ml and were significantly higher (P= 0.025) in the ischaemic stroke group when compared with the control group (0.1–0.3 pg/ml). Simultaneously acquired concentrations of 6‐keto‐PGF1α were not elevated in the stroke group when compared to normals.

4. These clinical findings support evidence from animal studies that emphasizes the importance of cerebral prostaglandins in mediating the secondary vascular changes of cerebral infarction. In conclusion there is an aberration in CSF thromboxane B2 concentrations in patients who have had a stroke. This may be an acute or chronic phenomenon.
PROPRANOLOL AMELIORATES EXERCISE‐INDUCED REGIONAL MYOCARDIAL DYSFUNCTION IN DOGS
Authors: Mayer N. , Krumpl G. , Schneider W. , Raberger G.
Published: June 2007

1. The effects of propranolol (0.5 mg/kg) on exercise‐induced regional myocardial dysfunction were investigated in an animal model with limited coronary reserve.

2. Limited coronary reserve was accomplished in conscious, chronically instrumented dogs by external filling of a hydraulic cuff occluder placed on a coronary vessel which did not impair resting myocardial function but induced severe dysfunction during treadmill exercise.

3. Propranolol led to a distinct reduction of heart rate, myocardial contractility and systolic blood pressure, thereby ameliorating exercise‐induced regional myocardial dysfunction.
THE EFFECT OF HIGH FREQUENCY OSCILLATORY VENTILATION ON EXTRAVASCULAR LUNG WATER IN THE RABBIT
Authors: Ritchie B. C. , Brodecky V. , Scott A. , Wilkinson M. H.
Published: June 2007

1. High frequency ventilation (HFV) systems have the theoretical advantage of producing less barotrauma and lung damage because of the associated smaller oscillations in alveolar pressure compared to conventional ventilators.

2. An index of lung damage is an increase in extravascular lung water but previous studies using HFV have produced conflicting results.

3. Lung wet‐to‐dry ratio, extravascular lung water and blood mass were measured in 30 rabbits divided into three groups (n= 10); spontaneously breathing (SV), conventional positive pressure ventilation (CV) and high frequency oscillatory ventilation (HFV).

4. HFV maintained normal blood gases and produced a significant reduction in the wet‐to‐dry weight ratio compared to SV and CV (P < 0.05). Extravascular lung water and blood mass were significantly reduced in HFV compared to SV (P < 0.05).

5. It is concluded that the system of HFV used in this study has clinical potential in the treatment of lung injury.
STREPTOKINASE ALTERS MYOCARDIAL CREATINE KINASE DEPLETION AFTER ISCHAEMIA AND REPERFUSION IN RABBITS
Authors: Mickelson J. K. , Carlson C. J. , Margaretten W. , Rapaport E.
Published: June 2007

1. The efficacy of streptokinase as an intracoronary thrombolytic agent is wellrecognized. The effect of streptokinase, distinct from its thrombolytic action, on ischaemic myocardium distal to an area of coronary artery occlusion when reperfusion occurs has not been well‐defined.

2. In order to do this, myocardial creatine kinase depletion and the histopathology of infarctions produced in rabbits after 1 h of circumflex coronary artery occlusion and mechanical release of the occlusion were assessed.

3. Streptokinase or saline was infused intravenously for 1 h beginning 0.5 h after occlusion. Rabbits were divided into two time intervals: early (<10 h) and late (24 h) after release of coronary artery occlusion.

4. When streptokinase was infused in early infarctions, haemorrhage did not correlate with infarction cross‐sectional area or myocardial creatine kinase depletion. However, myocardial creatine kinase depletion was 40% less when streptokinase was infused than when saline was infused, suggesting that streptokinase might limit infarct size.

5. In late infarctions, the degree of haemorrhage, infarction cross‐sectional area, and myocardial creatine kinase depletion were similar after reperfusion with streptokinase or saline. By 24 h, the beneficial effect of a single dose of streptokinase given early in the course of occlusion‐reperfusion myocardial injury was no longer evident in limiting infarct size.
NUCLEAR LOCALIZATION OF TYPE 1 ALDOSTERONE BINDING SITES IN STEROID‐UNEXPOSED GH3 CELLS
Authors: Pearce Paul T. , McNally Margaret , Funder John W.
Published: June 2007

1. The nuclear localization of unoccupied oestrogen receptors has been demonstrated in MCF 7 (human breast tumour) cells by immunocytochemistry, and in GH3 (rat pituitary tumour) cells by enucleation techniques.

2. The present study shows, by similar enucleation techniques, that high affinity (Type 1) aldosterone binding sites are similarly located in the nucleus of steroidunexposed pituitary GH3 cells.

3. It is, therefore, suggested that such high‐affinity Type 1 sites, which are mineralocorticoid receptors in the kidney and glucocorticoid receptors in the hippocampus, are nuclear‐associated proteins in the absence of steroid and are found in the cytosol compartment only upon cell disruption.
ACCELERATED PROGRESSION OF DIABETIC NEPHROPATHY IN THE SPONTANEOUSLY HYPERTENSIVE STREPTOZOTOCIN DIABETIC RAT
Authors: Cooper M. E. , Allen T. J. , Jerums G. , Doyle A. E.
Published: June 2007

1. Streptozotocin (STZ)‐diabetes was induced in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats with their litter mates serving as controls. The animals were studied for 6 months and blood pressure, weight, urinary and serum glucose, creatinine clearance, total proteinuria and albuminuria were measured monthly.

2. With induction of diabetes, there was a significant rise in creatinine clearance in the hypertensive diabetic animals (SHR‐STZ). SHR‐STZ (n= 6) developed higher levels of total proteinuria than WKY‐STZ (n= 5) although the rise from basal levels was only apparent after 20 weeks of diabetes. All SHR‐STZ developed albustix positive proteinuria after 6 months of diabetes.

3. In the first 12 weeks after onset of diabetes, albuminuria increased to a greater degree in SHR‐STZ than in WKY‐STZ. This occurred before there was a detectable rise in total proteinuria.

4. The SHR‐STZ model of genetic hypertension and diabetes may be suitable for the evaluation of antihypertensive therapy in human diabetic renal disease.
CHARACTERIZATION OF ANGIOTENSIN CONVERTING ENZYME FROM RAT TISSUE BY RADIO‐INHIBITOR BINDING STUDIES
Authors: Jackson Bruce , Cubela Rose , Johnston Colin I.
Published: June 2007

1. Angiotensin converting enzyme (ACE) derived from rat lung, aorta, epididymus, brain, kidney and plasma was characterized by radio‐inhibitor (125I‐MK351A) binding studies. Under optimal binding conditions at equilibrium 125I‐MK351A bound to ACE was displaced from ACE in a concentration related manner by unlabelled MK351A.

2. MK351A binding site concentration for each tissue and equilibrium dissociation constant (KD) was estimated by Scatchard analysis of binding data. Binding sites/mg protein was greatest in lung and least in brain. The KD for kidney ACE was significantly higher than that of lung, aorta, epididymus or brain ACE (P<0.005; t‐test, d.f. = 10).

3. 125I‐MK351A bound to ACE prepared from lung and kidney was displaced in a concentration dependent manner by SQ20881, SQ14225, MK422, and Ro31–3113–000. Concentration of ACE inhibitor required to displace 50% of bound 125I‐MK351A (DD50) was consistently higher for kidney‐derived ACE than lung‐derived ACE.

4. The differences in radio‐inhibitor binding characteristics of ACE from different rat tissues suggests that the enzyme active site may not be identical in all organs.