bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF ARACHIDONATE DEFICIENCY ON ENDOTHELIUM‐ DEPENDENT VASCULAR REACTIONS
Authors: Loiacono R. E. , Kudo K. , Dusting G. J. , Sinclair A. J.
Published: June 2007

1. The release of endothelium‐derived relaxing factor (EDRF), which appears to be impaired in vessels chronically exposed to hypertension, may involve mobilization of arachidonate from phospholipids. In this study the effects of arachidonate deficiency on endothelium‐dependent responses were examined in rat isolated aorta.

2. Weanling rats were fed an essential fatty acid‐deficient (EFAD) diet for 8 weeks which reduced plasma and aortic phospholipid arachidonate content from 17 to 1.8% and from 21 to 8%, respectively. After this time the rats were killed and the reactivity of aortic rings was studied in organ baths.

3. In aortic rings from control rats the concentration‐response curves for the contractile action of phenylephrine were shifted to the left 3.5‐fold by removal of the endothelium, and the maximum was not altered.

4. In contrast, in EFAD rings with endothelium, the maximal vasoconstriction to phenylephrine was less than in control rings, and removal of the endothelium increased the maximum (from 1.9±0.2 to 3.2±0.1 g, P < 0.05) and reduced the EC50 7‐fold.

5. In EFAD rings precontracted with phenylephrine (0.3 μml/l) the relaxations produced by the endothelium‐dependent dilator acetylcholine were not significantly different from those produced in control rings. The dilator actions of sodium nitroprusside were also similar in EFAD and control rings.

6. Thus, endothelium‐dependent dilatation in the aorta is not impaired by partial depletion of phospholipid arachidonate. However, contractile responses to α‐adrenoceptor agonists are depressed by spontaneously released EDRF in rat aorta, so that the results suggest that depletion of phospholipid arachidonate either augments spontaneous release of EDRF, or impairs EDRF inactivating mechanisms.
RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY
Authors: Sang Kim Hahn Le Quan , Elghozi Jean‐Luc , Meyer Philippe , Devynck Marie‐Aude
Published: June 2007

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects.

2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject.

3. These results are consistent with the hypothesis that angiotensin II causes a concentration‐dependent calcium mobilization.
STUDY OF RECEPTOR‐STIMULATED PHOSPHATIDYLINOSITOL HYDROLYSIS IN INTACT, PERFUSED RAT HEARTS
Authors: Woodcock Elizabeth A. , McLeod Jennifer K. , Smith A. Ian , Clark Michael G.
Published: June 2007

1. Phosphatidylinositol turnover has been measured in intact, perfused rat hearts by measuring generation of inositol phosphates following [3H]‐inositol labelling. Stimulation of accumulations of inositol wonophosphate, inositol bisphosphate and inositol tris phosphate were observed during perfusion with either noradrenaline (3×10‐5 mol/l) or carbachol (10‐3 mol/l).

2. Stimulation by noradrenaline was antagonized by prazosin (10‐7 mol/l) but not by propranolol (10‐7 mol/l), indicating mediation via α‐adrenoceptors. Stimulation by carbachol was antagonized by atropine (10‐7 mol/l).

3. Transmural electrical stimulation of the hearts failed to increase inositol phosphate accumulation through α1‐adrenoceptors. A small stimulation mediated by muscarinic receptors was observed. Therefore α1‐adrenoceptors which stimulate phosphatidylinositol turnover probably do not have a synaptic localization in heart.

4. The development of methods for the study of phosphatidylinositol turnover in intact hearts will facilitate an investigation of relationships between this signal transduction pathway and cardiac function.
HANDLING OF A SODIUM LOAD BY RATS ON A LOW SODIUM INTAKE AND FRUSEMIDE
Authors: Ledingham Janet M. , Simpson F. O.
Published: June 2007

1. Groups of rats (n= 9–10 per group) were given a medium sodium (Na) diet or a low Na diet or a low Na diet plus low or high dose frusemide in order to have their body Na in a state of surplus or deficit or neither.

2. Body Na was measured by a 22Na whole body counting method involving Na‐free chow and the drinking fluid as the only source of Na (22Na‐labelled NaCl). Intraperitoneal NaCl (same specific activity) loads were given and their excretion was measured by repeated measurements of body Na over the next 48 h.

3. Rats in surplus excreted more than the load; those in neither surplus nor deficit excreted more or less exactly the load (allowing for growth); those with a small deficit retained enough Na to make up most of the deficit; those with a deficit that was larger than the load retained approximately the whole load.

4. The results support the Strauss‐Hollenberg concept that there is a basal body Na above which Na is excreted and below which any available Na is retained.
ANGIOTENSIN II‐INDUCED CONTRACTION OF MESANGIAL CELLS IN ACUTE RENAL ARTERY STENOSIS IN DOGS
Authors: Anderson W. P. , Alcorn D. , Gilchrist A. I. , Ryan G. B.
Published: June 2007

1. Renal artery stenosis was induced in anaesthetized dogs, and the kidney rapidly fixed after 30 min.

2. Electron microscopy revealed marked folding of the paramesangial basement membrane in stenotic kidneys (n= 7). The extent of this folding was significantly less in dogs treated with captopril (n= 6).

3. It is suggested that this folding reflects angiotensin II‐induced contraction of the mesangial cells, which may help maintain glomerular filtration rate following stenosis.
CHANGES IN THE CONTENT OF DOPAMINE AND ITS METABOLITES IN THE BASAL GANGLIA FOLLOWING RIGHT MIDDLE CEREBRAL ARTERY OCCLUSION AND REFLOW IN MONKEYS
Authors: Kuruvilla Alice , Cherian Rebecca , Theodore Deepa , Abraham Jacob
Published: June 2007

1. Focal ischaemia was produced experimentally in Macaca radiata monkeys by occlusion of middle cerebral artery (MCA). There was a lowering of the dopamine (DA) content of basal ganglia after 4 and 12 h of occlusion.

2. DA content was restored to normal in basal ganglia after restoration of blood flow. With the progress of time the DA content was increased above that of sham controls. Changes were also observed in the non‐occluded left basal ganglia.

3. The homovanillic acid (HVA) content was decreased significantly at 12 h after occlusion. After the onset of reflow, the HVA content of the right basal ganglia was higher than that of sham controls.

4. The 3, 4 dihydroxyphenylacetic acid (DOPAC) content of right basal ganglia was significantly decreased after 12 h occlusion. Reflow restored the level of DOPAC to normal within 1 h after removal of clip.

5. Discrete changes were also observed in the left basal ganglia at some of the time intervals.
IN VIVO ESTIMATION OF CHANGES IN DISTAL TUBULE FLOW AND THEIR ROLE IN DEXAMETHASONE‐INDUCED KALIURESIS IN CONTROL AND POTASSIUM‐ADAPTED RATS
Authors: Adam William R. , Adams Beverlie A. , Ellis Andrew G.
Published: June 2007

1. The aim of this study was to determine whether the kaliuresis associated with glucocorticoids is due to a direct tubular action or is secondary to effects of glucocorticoids on distal tubule flow.

2. A whole kidney technique was used to avoid the problem, inherent in microperfusion and micropuncture studies, of deciding whether (all) the appropriate nephron segment(s) are being studied.

3. The method used was to determine the best whole kidney measure of distal tubule flow (the independent variable) by correlating this with the dependent variable (potassium excretion, corrected for differences in plasma potassium, UkV/PlK+) in conscious intact and adrenalectomized control and potassium‐adapted rats.

4. After an intragastric potassium chloride load, the correlation of UkV/PlK+ with UkV + UNaV was better than with either UNaV or UV, as measures of distal tubule flow. From the relationship a measure of potassium excretion independent of distal tubule flow can thus be calculated as UkV/PlK+÷ (UkV + UNaV), defined as UK#.

5. Measurement of UK# clearly demonstrates decreases in potassium excretion with adrenalectomy and increases in potassium excretion with aldosterone and in the potassium‐adapted rat, consistent with described changes in potassium secretion. In contrast, with dexamethasone treatment, whilst there was an increase in UkV and UkV/PIK+, there was no change in UK# either in the control of potassium‐adapted rats.

6. These results suggest that the kaliuretic effect of dexamethasone cannot be attributed to direct tubular effects of glucocorticoids but rather can be explained by its effect on distal tubule flow.
THE EFFECTS OF CALCIUM ANTAGONISTS ON BLOOD PRESSURE AND RESPONSES TO α‐ADRENOCEPTOR AGONISTS IN HYPERTENSIVE RABBITS
Authors: Hamilton C A. , Jardine E. , Sumner D. J. , Reid J. L.
Published: June 2007

SUMMARY

1. The effects of the calcium antagonists verapamil and nifedipine on mean arterial blood pressure, heart rate and pressor responses to a range of α‐adrenoceptor agonists were examined in male normotensive New Zealand white rabbits and in rabbits with perinephritis hypertension.

2. Verapamil and nifedipine caused a greater fall in mean arterial pressure in hypertensive compared to normotensive rabbits both when the fall was expressed as an absolute and as a percentage change. Effects on heart rate were similar in normotensive and hypertensive animals.

3. Pressor responses to phenylephrine were attenuated by nifedipine and verapamil in normotensive and hypertensive rabbits. Pressor responses to alphamethyl noradrenaline were also attenuated by nifedipine, but pressor responses to BHT 920 were not significantly altered by either calcium antagonist in normotensive or hypertensive rabbits at the dose used. Thus the calcium antagonists had a greater effect on α1‐than α2‐adrenoceptor mediated responses in both normotensive and hypertensive rabbits.

4. Hypertensive animals showed an increased responsiveness to phenylephrine and alphamethyl noradrenaline but not BHT 920 compared to normotensives. This difference remained after treatment with both the calcium antagonists.
COMBINED BRONCHODILATOR PROTECTION AGAINST HISTAMINE‐INDUCED BRONCHOCONSTRICTION IN MAN
Authors: Ruffin R. E. , Meki M. , Alpers J. H.
Published: June 2007

SUMMARY

1. Sixteen stable asthmatics had the protective effects of inhaled fenoterol (200 μg) and inhaled ipratropium bromide (60 μg) against standardized histamine inhalation tests at 1 h examined in a randomized double blind fashion.

2. There was no significant difference in the baseline forced expired volume in 1 s (FEV1) for the two study days (P >0.05).

3. There was an increase in FEV, at 1 h on the fenoterol and ipratropium day compared with the fenoterol day (0.26 versus 0.17 1; P < 0.05).

4. The geometric mean provocative concentration of histamine to cause a 20% fall in FEV, (PC20) was 6.31 mg/ml after fenoterol and 8.51 mg/ml after fenoterol and ipratropium (P= 0.038).

5. There was no significant relationship between bronchodilator effect of the bronchodilators and the increase in PC20 from pre‐study values, r= 0.307 (P=0.25) for fenoterol alone and r=0.195 (P=0.47) for fenoterol and ipratropium.

6. The relationship between pre‐study histamine responsiveness and the increase in PC20 caused by the bronchodilators just failed to reach statistical significance, r= ‐0.441 (P= 0.09) for fenoterol alone and r= ‐0.47 (P=0.06) for fenoterol and ipratropium.

7. The study has shown a greater right shift of histamine responsiveness for combined inhaled fenoterol and ipratropium compared with inhaled fenoterol alone in this group of asthmatics.
THE EFFECT OF β‐ADRENOCEPTOR BLOCKERS ON THE ABSORPTION AND EXCRETION OF CHLOROTHIAZIDE IN MAN
Authors: Adebayo G. I. , Oyenuga A. B. , Mabadeje A. F. B.
Published: June 2007

SUMMARY

1. The effect of β‐adrenoceptor blockers on the absorption and elimination of the diuretic chlorothiazide was studied in healthy subjects.

2. A week of pretreatment with either pindolol (10 mg twice daily) or propranolol (80 mg twice daily) resulted in significant reduction in 36 h mean cumulative urinary recovery of chlorothiazide in two groups of six subjects compared with a control (untreated) group.

3. A week of pretreatment with atenolol (100 mg daily) did not significantly alter 36 h cumulative urinary excretion in another group of six subjects.

4. None of the β‐blockers significantly changed chlorothiazide half‐life.

5. It is suggested that the non‐selective (as opposed to the cardioselective) β‐blockers reduce chlorothiazide absorption by the mechanism(s) discussed.
THE EFFECTS OF NALOXONE, DEXAMETHASONE, DEOXYCORTICOSTERONE AND 17‐HYDROXYPROGESTERONE ON BLOOD PRESSURE RESPONSES OF NORMAL AND ADRENALECTOMIZED RATS DURING HYPOVOLAEMIC SHOCK
Authors: Khalid B. A. K. , Moral Paden , Merican Zainuddin
Published: June 2007

SUMMARY

1. The roles of, and interactions between, steroids and naloxone, an opioid antagonist, in the reversal of experimental hypotensive shock were studied in normal and adrenalectomized rats.

2. In normal rats treated with dexamethasone or deoxycorticosterone or 17‐hydroxyprogesterone the hypotension and shock caused by 1% bodyweight and 2% bodyweight haemorrhage could be substantially reversed by naloxone in a dose‐related manner. In contrast, the reversal of hypotension by naloxone was markedly less in adrenalectomized rats.

3. It is concluded that there is a co‐ordinate release of pressor catecholamines and depressor enkephalins from adrenal glands in hypovolaemic shock. Eventually, the use of naloxone would be of much less value in the treatment of hypotension or shock in patients with Addison's disease.
MICROINJECTION OF KAINIC ACID INTO THE ROSTRAL VENTROLATERAL MEDULLA CAUSES HYPERTENSION AND RELEASE OF NEUROPEPTIDE Y‐LIKE IMMUNOREACTIVITY FROM RABBIT SPINAL CORD
Authors: Morris M. J. , Pilowsky P. M. , Minson J. B. , West M. J. , Chalmers J. P.
Published: June 2007

SUMMARY

1. Microinjections of kainic acid were made into the pressor area of the rostral ventrolateral medulla oblongata of anaesthetized rabbits, in the region of the C1 adrenaline‐containing neurons.

2. Over the 65 min following the microinjection, there was a significant increase in blood pressure, as well as an increase in the release of neuropeptide Y‐like immunoreactivity into the spinal subarachnoid space.

3. These data provide evidence for a functional bulbospinal neuropeptide Y‐containing projection which may be responsible for mediating the pressor effects of stimulation of the rostral ventrolateral medulla.
MODULATION OF RENAL NORADRENALINE RELEASE BY PREJUNCTIONAL RECEPTOR SYSTEMS IN VITRO
Authors: Rump L. C.
Published: June 2007

SUMMARY

1. The amount of noradrenaline released per nerve impulse from renal sympathetic nerves can be modulated through specific prejunctional receptors.

2. Under in vitro conditions activation of α1, α2‐, prostaglandin, adenosine, dopamine and serotonin receptors inhibits noradrenaline release from the kidney.

3. Stimulation of prejunctional β‐adrenoceptors, probably of the β2‐subtype, as well as stimulation of prejunctional angiotensin II receptors facilitates noradrenaline release. Moreover, neuronally released noradrenaline inhibits its own release through activation of both prejunctional α1‐and α2‐adrenoceptors.

4. Locally produced PGE2, which is formed and released via stimulation of postjunctional α1‐adrenoceptors, as well as adenosine, released from postjunctional sites by renal nerve stimulation (RNS), seems to inhibit noradrenaline release through their specific prejunctional receptor systems.
AUTORADIOGRAPHIC LOCALIZATION OF RECEPTORS IN THE MAMMALIAN CARDIOVASCULAR SYSTEM
Authors: Summers R. J. , Molenaar P. , Stephenson J. A. , Jones C. R.
Published: June 2007

SUMMARY

1. Autoradiographic techniques have been used to examine the location of β‐adrenoceptors in the heart and β‐adrenoceptors, substance P receptors and muscarinic cholinoceptors in blood vessels.

2. Both β1‐adrenoceptors and β2‐adrenoceptors were present in guinea‐pig and human heart, on the myocardium and associated with the cardiac nerves and blood vessels.

3. Nerves on the vasculature and vascular smooth muscle contained β‐adrenoceptors and muscarinic cholinoceptors.

4. Receptors for substance P and β‐adrenoceptors, but not muscarinic cholinoceptors were present on endothelial cells.
SENSITIVITY CHANGES OF THE PERFUSED HINDQUARTERS’ VASCULATURE IN RATS WITH ALLOXAN‐INDUCED DIABETES MELLITUS
Authors: Boura A. L. A. , Hodgson W. C. , King R. G.
Published: June 2007

SUMMARY

1. Arachidonic acid (AA, 0.125–1.0 mg/kg) injected via the aorta into the autoperfused hindquarters caused dose‐dependent increases in perfusion pressure. This effect was reduced after intravenous administration of the thromboxane receptor antagonist AH23848 (5 mg/kg) or indomethacin (5 mg/kg).

2. Responses to AA (0.125–1.0 mg/kg) were reduced markedly in the Krebs‐perfused hindquarters when compared with those occurring in the blood‐perfused preparation.

3. Doses of guanethidine (1 mg/kg) and pentacynium (1 mg/kg) blocking pressor responses to intravenous administration of the ganglion stimulants McN‐A‐343 and DMPP, respectively, did not affect responses to AA.

4. Constrictor responses to AA (0.5–1.0 mg/kg) in blood‐perfused hindquarters were increased in 14 day alloxan‐diabetic rats but those to the thromboxane A2‐mimetic U46619 (0.5–8.0 μg/kg, i.a.) were reduced when compared with non‐diabetic controls.

5. In 14 day alloxan‐diabetic rats vasoconstrictor responses to noradrenaline and methoxamine were potentiated but those to 5‐hydroxytryptamine were reduced compared with non‐diabetic animals.

6. It is concluded that AA causes constriction in the blood‐perfused hindquarters by release of a product of cyclo‐oxygenase acting on thromboxane A2‐receptors. A constituent of blood, perhaps the platelet, appears necessary for this effect. Conversion of AA to the constrictor metabolite is augmented during experimentally induced diabetes.
EFFECTS OF ANGIOTENSINS II AND III ON GLOMERULOTUBULAR BALANCE IN RATS
Authors: Harris Peter J. , Zhuo Jialong , Skinner Sandford L.
Published: June 2007

1. The role of angiotensin as a modulator of proximal glomerulotubular (GT) balance was investigated in anaesthetized rats by examining the relationship between glomerular filtration rate (GFR) and absolute proximal reabsorption (APR) during removal of endogenous angiotensin II (AII) and III (AIII) with enalaprilat (CEI) and then during their subsequent replacement by intravenous infusions.

2. Enalaprilat lowered mean arterial blood pressure (MABP) and increased renal blood flow (RBF), GFR, urine flow rate and sodium excretion. Filtration fraction (FF) was not altered. Absolute proximal reabsorption, derived from fractional lithium clearance, increased by only 48% of the change expected for ‘perfect’ GT balance.

3. Angiotensin II replacement corrected MABP, GFR and plasma renin level, but reduced RBF and increased FF; APR was decreased and GT balance was restored. Urine flow and sodium excretion remained above control values with AII.

4. Replacement with AIII did not correct the hypotension but completely reversed the renal and renin responses to enalaprilat and restored GT balance without affecting FF.

5. It was concluded that the relation between proximal reabsorption and GFR is considerably modified by the intrarenal angiotensin concentration. The findings are best explained by a direct stimulation of proximal tubular sodium transport by angiotensin at the concentrations existing in anaesthetized rats.
β‐ADRENOCEPTORS ON ENDOTHELIAL CELLS DO NOT INFLUENCE RELEASE OF RELAXING FACTOR IN DOG CORONARY ARTERIES
Authors: Macdonald Peter S. , Dubbin Philip N. , Dusting Gregory J.
Published: June 2007

1. The aim of this study was to determine if stimulation of a β‐adrenoceptor on endothelial cells could release an endothelium‐derived relaxing factor (EDRF) similar to that released by acetylcholine.

2. In dog coronary rings preconstricted with PGF2α or serotonin, removal of the endothelium did not alter the relaxant responses to isoprenaline. However, in rings preconstricted with the thromboxane‐mimetic U46619, removal of the endothelium enhanced the response to isoprenaline.

3. The vasorelaxant responses to isoprenaline in endothelium‐denuded rings were inhibited in a concentration‐dependent manner by the specific β1‐adrenoceptor antagonist CGP‐20712A (3–100 nmol/l), but were not altered by the β2‐adrenoceptor antagonist ICI‐118551 (30 nmol/l).

4. The vasorelaxant responses to isoprenaline in the presence of CGP‐20712A (30 nmol/l) or ICI‐118551 (30 nmol/l) were not impaired by removal of the endothelium.

5. Endothelium‐dependent vasorelaxant responses to acetylcholine and bradykinin were not altered by isoprenaline (0.1 μmol/l) in the presence of CGP‐20712A (30 nmol/l).

6. Therefore, the β‐adrenoceptors on dog coronary artery smooth muscle which produce relaxation are predominantly of the β1‐subtype. Stimulation of any β2‐adrenoceptors on the endothelium in dog coronary artery does not release EDRF, and does not modulate endothelium‐dependent vasodilatation induced by other agents.
EFFECTS OF PANAX GINSENG ON BLOOD ALCOHOL CLEARANCE IN MAN
Authors: Lee F. C. , Ko J. H. , Park J. K. , Lee J. S.
Published: June 2007

1. Fourteen healthy male volunteers were studied to assess the effects of Panax ginseng on blood alcohol clearance, utilizing each subject as his own control.

2. At 40 min after the last drink, the blood alcohol level in the test group receiving ginseng extract (3 g/65 kg body weight) along with alcohol (72 g/65 kg body weight) was about 35% lower than their control values.

3. When the blood alcohol level was compared on individual bases, alcohol concentrations in 10 out of 14 test subjects ranged from 32 to 51% lower than their control values.

4. These results demonstrate that P. ginseng extract enhances blood alcohol clearance in man.
CHRONOTOXICITY OF β‐ADRENOCEPTOR BLOCKING AGENT IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Fujimura Akio , Ebihara Akio
Published: June 2007

1. Chronotoxicity of a single LD50 dosage of β‐adrenoceptor blocking agent, pindolol, was determined in spontaneously hypertensive rats (SHR) and Wistar‐Kyoto control rats (WKY).

2. The 24 h mortality was greater when pindolol was administered at 00.00 h than when it was administered at 12.00 h in both SHR and WKY.

3. The chronogram of the mortality in SHR was similar to that in WKY.

4. These results indicate that the mode of circadian variation in the acute toxicity of pindolol in SHR is not different from that in WKY.
THE HAEMODYNAMIC EFFECTS OF CYCLOSPORIN A IN SHEEP
Authors: Whitworth Judith A. , Mills Eric H. , Coghlan John P. , McDougall John G. , Nelson Mark A. , Spence Campbell D. , Tresham Janette J. , Scoggins Bruce A.
Published: June 2007

SUMMARY

1. Cyclosporin A (CyA; 12 mg/kg/day) was infused into six conscious sheep over 5 days to examine the haemodynamic effects of the drug in normal animals.

2. Mean arterial pressure was increased from 73(1) mmHg to 90(4) mmHg (P < 0.001). There was no change in cardiac output but calculated total peripheral resistance was elevated from 16(1) to 21(2) mmHg min/1 (P < 0.001) on day 4.

3. There was no change in plasma [Na], but a fall in plasma [K]. Urinary Na excretion decreased. Glomerular filtration rate, filtration fraction, renal blood flow, renal vascular resistance, body weight, plasma renin and blood aldosterone concentration were unchanged.

4. CyA produces an increase in blood pressure in sheep associated with an increase in total peripheral resistance on days 1, 3, and 4, in the absence of changes in renal function. This suggests that CyA hypertension is not simply a consequence of nephrotoxicity.
RENAL RESPONSES TO ANGIOTENSIN II IN CONSCIOUS DOGS: EFFECTS OF ASPIRIN AND INDOMETHACIN
Authors: Anderson W. P. , Selig S. E. , Woods R. L. , Gilchrist A. I.
Published: June 2007

1. Angiotensin II was infused into the renal artery of unanaesthetized dogs at 0.4 and 2.0 ng/kg per min for 40 min each.

2. Indomethacin (3 mg/kg, and 1 mg/kg per h infusion i.v.) accentuated the angiotensin II‐induced falls in glomerular filtration rate, renal blood flow and urine flow rate. Indomethacin did not alter the effects of angiotensin II on Na+ or K+ excretions.

3. Aspirin (35 mg/kg p.o. 2.5 h and 0.5 h prior to experiment) did not significantly change the renal effects of angiotensin II.

4. Both aspirin and indomethacin accentuated renal vasoconstriction during briefer (5 min) angiotensin II infusion.

5. Thus indomethacin and aspirin had markedly different effects on the actions of angiotensin II in the kidney. This suggests that at least one of these drugs has actions which affect angiotensin II‐mediated vasoconstriction other than via cyclooxygenase inhibition.
CHARACTERIZATION AND LOCALIZATION OF (—‐)[125I]‐CYANOPINDOLOL BINDING TO NON‐β‐ADRENOCEPTOR SITES IN DOG KIDNEY
Authors: Lew R. , Summers R. J.
Published: June 2007

1. (—)[125I]‐Cyanopindolol (CYP) binding to non‐β‐adrenoceptor sites in dog kidney was characterized in homogenate preparations and their distribution in sections determined using autoradiography.

2. In homogenate studies, (—)[125I]‐CYP bound to a single population of non‐interacting sites (Bmax= 5.45, s.e.m. = 1.00 fmol/mg wet weight; nH = 0.99, s.e.m. = 0.01) with high affinity (KD= 3.84, s.e.m. = 0.76 nmol/l, n= 4).

3. In competition studies, compounds selective for α‐ and β‐adrenoceptors, muscarinic cholinoceptors and receptors for 5‐HT, histamine and benzodiazepines, calcium channel antagonists, catecholamine uptake inhibitors, MAO inhibitors and adrenergic neurone blockers were ineffective at concentrations of 10 μmol/l.

4. Compounds selective for dopamine D1‐receptors (fluphenazine, SCH 23390 and SK & F 82526) and D2‐receptors (pimozide, domperidone, spiperone, haloperidol, sulpiride, cis‐ and trans‐flupenthixol) competed with similar affinities (5–25 μmol/l) for (—)[125I]‐CYP binding.

5. In autoradiographic studies, (—) [125I]‐CYP binding to non‐β‐adrenoceptor sites was localized over glomeruli, juxtaglomerular apparatus, distal tubules, blood vessels and medullary rays and tubules.

6. It is concluded that in dog kidney, (—)[125I]‐CYP binds to a site closely associated with dopamine receptors.
THE EFFECT OF SUBDIAPHRAGMATIC VAGOTOMY ON THE GASTRIC MUCUS BARRIER IN RATS
Authors: Somasundaram K. , Ganguly A. K.
Published: June 2007

1. Little information exists on the quantitation of mucus barrier and its vagal control; hence, the effect of vagotomy on the two components of the mucus barrier was studied in the glandular regions of rat stomach.

2. Bilateral subdiaphragmatic vagotomy was carried out by cutting both vagus nerves at the level of the lower end of the oesophagus. After 14 days, the glycoproteins in mucosal epithelial cells were identified by periodic acid Schiff's (PAS) staining technique and were assessed by calculating the ratio of the mucosal height to that of the thickness of PAS‐positive materials in it. The adherent mucus was estimated by the Alcian blue binding technique and the results were compared with control animals subjected to mock vagotomy.

3. The bilateral subdiaphragmatic vagotomy caused a significant reduction in mucosal epithelial PAS‐stainable materials content in oxyntic and pyloric gland areas.

4. The operation also caused a decrease in Alcian blue binding capacity of both the glandular regions.

5. The data suggest that the absence of vagal influence causes weakening of both the lines of mucus barrier. The findings support the hypothesis that the vagal system must be intact in the rat in order to maintain gastric mucus glycoproteins and thereby mucosal integrity.
EFFECTS OF CYCLOSPORIN A, GENTAMICIN AND FUROSEMIDE ON RAT RENAL FUNCTION: A LITHIUM CLEARANCE STUDY
Authors: Dieperink Hans , Leyssac Paul P. , Starklint Henrik , Kemp Ejvind
Published: June 2007

1. This study applied clearance methods of inulin, lithium, potassium, sodium and para‐aminohippuric acid (PAH) for investigation of the effects of cyclosporin A (CyA), furosemide and gentamicin on rat (n= 92) renal function. The drugs were dosed for 2 weeks; CyA 12.5 mg/kg per day, gentamicin 32 mg/kg per day and furosemide 5 mg/kg per day.

2. The questions asked were: could these methods differentiate the effects of drugs with different sites of action, and would gentamicin or furosemide exaggerate the nephrotoxicity of CyA?

3. Furosemide increased sodium clearance (CNa) 74% and fractional sodium clearance (FENa) 105%, while fractional sodium reabsorption in the distal nephron (FDNR) was reduced, compared with placebo‐treated controls.

4. Gentamicin reduced CPAH29% and Cin37%, while FENaincreased 335%. Proximal fractional reabsorption (PFR) and absolute proximal reabsorption (APR) decreased.

5. CyA depressed CPAH32% and lithium clearance (CLi) 56%, and increased PFR.

6. The effects of CyA and furosemide in reducing renal function were not additive.

7. CyA plus gentamicin reduced CPAHto 35% of the value in untreated controls, equal to 52% of the CPAHof CyA‐treated rats; Cinwas reduced to 46% of the Cinof CyA‐treated rats.

8. Rats given CyA, furosemide and gentamicin had decreased Cin, CPAH and CLicompared with rats given either CyA plus furosemide or gentamicin plus furosemide.

9. Thus, in this investigation of drugs known to have different sites of actions, the differences in renal and tubular function were discernible with the lithium clearance method.

10. The nephrotoxicities of CyA and of gentamicin were additive, while furosemide did not aggravate CyA nephrotoxicity.
THE α2‐ADRENOCEPTOR AGONISTS CLONIDINE TL99 AND DPI ENHANCE VASOCONSTRICTOR RESPONSES TO SYMPATHETIC NERVE STIMULATION AND NORADRENALINE IN THE RAT TAIL ARTERY PREPARATION
Authors: Xiao X‐H. , Medgett I. C. , Rand M. J.
Published: June 2007

1. Clonidine (1–30 nmol/l) enhanced the vasoconstrictor responses to sympathetic nerve stimulation in isolated perfused artery preparations from the rat tail. Higher concentrations of clonidine produced vasoconstriction in most artery preparations and reduced the response to sympathetic nerve stimulation.

2. The enhancing effect of clonidine was not affected by prazosin but was blocked by idazoxan, indicating that it was due to activation of α2‐adrenoceptors.

3. The α2‐adrenoceptor agonists DPI and TL99, like clonidine, enhanced vasoconstrictor responses to sympathetic nerve stimulation.

4. Vasoconstrictor responses to noradrenaline were enhanced by clonidine and TL99.

5. The findings suggest that activation of postjunctional α2‐adrenoceptors results in facilitation of the contractile response elicited by activation of α1‐adrenoceptors.
EFFECTS OF NALOXONE ON GLUCOSE LEVEL IN THE HEPATIC VENOUS PLASMA IN THE RAT
Authors: Pacula Piotr , Janicki Piotr K. , Krząścik Pawel
Published: June 2007

1. The effect of opioid receptor blockade by naloxone in vivo on hepatic venous plasma glucose concentration in rats was investigated.

2. The plasma glucose levels in naloxone‐injected animals (10 mg/kg) were higher than in the control animals (P < 0.05).

3. At the lower dose of naloxone (2 mg/kg) the resulting plasma glucose concentration did not differ significantly from control (P > 0.1).

4. It is concluded that endogenous opioids may moderate the regulation of basal glucose levels in the rat.
EFFECTS OF ZSY‐27, A SYNTHESIZED PHOSPHODIESTERASE INHIBITOR, ON EXOCRINE SECRETION AND CYCLIC NUCLEOTIDE CONCENTRATION IN THE DOG PANCREAS
Authors: Iwatsuki K. , Horiuchi A. , Chiba S.
Published: June 2007

1. Effects of intravenous injections of ZSY‐27, a synthesized phosphodiesterase inhibitor, on pancreatic exocrine secretion and on pancreatic cyclic AMP and cyclic GMP concentrations of dogs were investigated.

2. ZSY‐27 (0.3 and 1 mg/kg) increased cyclic AMP concentration dose‐dependently, which preceded the increase in pancreatic secretion but did not affect cyclic GMP concentration.

3. These results suggest that ZSY‐27 causes exocrine secretion from the dog pancreas mediated through an increase in intracellular cyclic AMP concentration.
INVOLVEMENT OF α1‐ADRENOCEPTORS IN CHRONOTROPIC RESPONSES TO ENDOGENOUSLY RELEASED AMINES IN THE PITHED RAT
Authors: Luca A. De , Rand M. J.
Published: June 2007

1. In pithed rats, yohimbine (1 mg/kg i.v.) enhanced the positive chronotropic responses to spinal stimulation of cardiac sympathetic nerves with eight pulses delivered at 2 or 4 Hz, indicating that auto‐inhibition was operating, but did not increase responses to shorter lengths of trains of 8 pulses at 8, 16 or 32 Hz which did not allow sufficient time for auto‐inhibition to come into effect.

2. The positive chronotropic response to cardiac sympathetic nerve stimulation with eight pulses at 8 Hz of about 60 beats/min was not affected by prazosin (1 mg/kg) or diltiazem (0.2 mg/kg), but was reduced to about 20% of the control value by propranolol (1 mg/kg).

3. In the presence of propranolol, the residual positive chronotropic responses to cardiac sympathetic nerve stimulation were virtually abolished by prazosin (1 mg/kg) or diltiazem (0.2 mg/kg).

4. The positive chronotropic response to tyramine (0.1 mg/kg i.v.) was reduced from 100 to 12 beats/min by propranolol (1 mg/kg), and the residual response was abolished by prazosin.

5. The findings indicate that noradrenaline released from cardiac sympathetic terminals by nerve stimulation or by tyramine acts on α1‐adrenoceptors to produce a positive chronotropic response that is revealed when β‐adrenoceptors are blocked.
BLOOD PRESSURE, SALT APPETITE AND MORTALITY OF GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS MAINTAINED ON HIGH AND LOW SALT DIETS FROM WEANING
Authors: Di Nicolantonio R. , Silvapulle M. J.
Published: June 2007

1. Blood pressure, bodyweight, saline preference and mortality rate were examined in spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control Wistar‐Kyoto (WKY) rats maintained on low (0.1% NaCl w/w), control (0.8% w/w) and high (3% w/w) salt diets from weaning until 6 months of age.

2. The growth rate of SHR on high salt diet was not significantly different from that on control diet but SHR maintained on a low salt diet exhibited a markedly reduced growth rate. While the growth rate of WKY on low salt diet was not significantly different from that on control diet, the body weights of WKY on high salt diet were significantly greater than those of animals on control diet.

3. While low salt diet markedly attenuated the development of hypertension in the SHR, high salt diet significantly exacerbated the blood pressure of this strain. Neither high nor low salt diet altered the blood pressure of WKY.

4. SHR on high and low salt diets had an increased mortality rate compared with SHR on control salt diet but these differences were of slight statistical significance. Conversely, WKY on all three diets exhibited similar mortalities over the 6‐month observation period. There were no significant differences in mortalities between SHR and WKY on any diet.

5. The preference for 0.9% saline, when offered as a choice with water, was not significantly different between SHR on the different diets. WKY on high salt diet, however, exhibited a significantly reduced preference for saline over the 10‐day test period compared with animals on control or low salt diet.

6. Thus dietary salt modulates the hypertension of SHR but not the blood pressure of WKY. SHR would appear to require more dietary sodium for normal growth and perhaps full expression of its hypertension. The higher and lower blood pressures of the SHR on high and low salt diet, respectively, were associated with increased mortality, which was a trend not seen in the WKY.
EFFECT OF POTASSIUM LOADING ON BONE SODIUM AND TOTAL EXCHANGEABLE SODIUM IN SHEEP
Authors: Reid Amanda F. , Coghlan John P. , McDougall John G. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. The effect of potassium (K) loading for 10 days on bone sodium (Na) and total exchangeable Na in sheep was examined.

2. There were no significant changes in Na space or exchangeable Na after K loading.

3. Bone Na concentration decreased by approximately 20% after K loading.

4. The degree of mobilization of Na from both the non‐exchangeable and exchangeable pools in bone is sufficient to account to a large degree for the observed increase in extracellular fluid volume and the net negative sodium balance which is observed during K loading.
SHORT COMMUNICATION: CATECHOLAMINE CONCENTRATIONS DURING EXPOSURE OF RESTING MAN TO THE HEAT OF A STANDARD SWEAT TEST
Authors: Wilkinson Ruth , Johnson Ralph H.
Published: June 2007

1. Normal subjects were heated for 45 min with a heat cradle under the conditions used to investigate sweating clinically.

2. Skin temperatures on the chest and in the external auditory meatus rose but concentrations of noradrenaline and adrenaline decreased during heating.

3. There was no change in adrenoceptor affinity or number as a result of the heat exposure.

4. There was little change in blood pressure and heart rate and no dysrhythmias were observed with an electrocardiogram.

5. It is concluded that heating with a heat cradle is generally not stressful and that there is a reduction in sympathetic nervous activity involving noradrenergic or adrenergic transmission during the procedure.
INFLUENCE OF BILE ACIDS ON THE BILIARY TRANSPORT MAXIMUM OF PHENOLSULPHONPHTHALEIN IN THE RAT
Authors: Collado P. S. , Muñoz M. E. , Esteller A. , González J.
Published: June 2007

1. The effect of changes in bile acid secretion induced by cholestyramine treatment or taurocholate infusion on the biliary transport maximum (Tm) of phenolsul‐phonphthalein (PSP) was studied in Wistar rats.

2. Five hours after oral administration of cholestyramine (1.5 g/kg bodyweight) the biliary output of bile acids decreased to 51% and bile flow to 76% of control values. The percentage of conjugated and unconjugated PSP excreted into bile and the Tm of the dye were not significantly modified by cholestyramine pretreatment.

3. Administration of sodium taurocholate at increasing rates (60–480 nmol/100 g bodyweight per min) enhanced bile flow and the biliary output of bile acids in a linear dose‐related fashion. The Tm of PSP increased progressively until a maximum of 29% above the control values was reached at a taurocholate dose of 240 nmol/100 g body‐weight per min). The enhancement corresponded mainly to the unconjugated dye, the excretion of conjugated PSP not being significantly modified by the infusion of the bile acid.

4. The results indicate that bile acids can influence to some extent biliary excretion of PSP in the rat, although this component is of minor importance at low bile acid secretory rates.
EFFECTS OF PROSTAGLANDIN D2 AND OMEPRAZOLE ON INDOMETHACIN‐INDUCED GASTRIC ULCERS IN RATS
Authors: Fukui Akira , Nakazawa Saburo , Goto Hidemi , Sugiyama Satoru , Ozawa Takayuki
Published: June 2007

1. The mechanism of indomethacin‐induced gastric ulcers was investigated by measuring tissue prostaglandins (PG) levels.

2. The effects of PGD2 and omeprazole, an H+ pump inhibitor, were also estimated.

3. Four kinds of PG—6‐keto PGF1α, PGF2α, PGE2, and PGD2—in rat gastric mucosa were measured by high performance liquid chromatography.

4. All PG levels decreased 1 h after oral administration of 2 mg/kg indomethacin, although they recovered considerably 24 h after administration. No gastric ulcers were observed throughout the experiments in rats treated with 2 mg/kg indomethacin.

5. All PG were not detected 1 h, and even 24 h after administration of 12 mg/kg indomethacin. Over 6 h after administration, gastric ulcers were observed.

6. Premedication with omeprazole prevented ulcer formation, although it did not improve gastric mucosal PG levels. Administration of PGD2 also reduced ulcer formation, and considerable amounts of PGD2 in gastric mucosa were detected.

7. It can be concluded that H+ is a determining factor in the genesis of indomethacin‐induced gastric ulcers and that persistent decreases in tissue PG levels also participate in ulcer formation.
EFFECT OF FURAZOLIDONE AND NITROFURAZONE ON BRAIN GAMMA‐AMINO BUTYRIC ACID AND GLUTAMATE CONCENTRATIONS IN CHICKENS
Authors: Ali B. H.
Published: June 2007

1. The concentrations of gamma‐amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days.

2. At the end of the treatment, birds on the small dose of FZ or NF lost about 9% of their bodyweight, and those on the high doses lost about 18%.

3. Both drugs produced dose‐dependent increases in the concentrations of GAA and glutamate which were statistically significant at doses of 25 and 50 mg/kg of NF and 50 mg/kg of FZ.
ENDOTHELIUM‐DERIVED RELAXING FACTOR RELEASED FROM CULTURED CELLS: DIFFERENTIATION FROM NITRIC OXIDE
Authors: Dusting G. J. , Read M. A. , Stewart A. G.
Published: June 2007

1. Endothelium‐derived relaxing factor (EDRF) is an extremely labile mediator thought to be identical to nitric oxide (NO).

2. A cascade superfusion technique was used to bioassay EDRF released from bovine aortic endothelial cells grown to confluence on microcarrier beads.

3. Bradykinin (1–100 nmol/1), infused through a 1 cm column of endothelial cells on microcarriers, released an EDRF‐like substance that caused relaxations of de‐endothelialized strips of rabbit aorta (precontracted with phenylephrine). These relaxations diminished on successive tissues in the cascade, when compared with those produced by glyceryl trinitrate as a stable standard.

4. Haemoglobin (1 μmol/1), infused directly over the bioassay tissues, abolished bradykinin‐induced relaxations and these were restored within 5 min after removal of haemoglobin. The infusion did not affect the relaxations produced by glyceryl trinitrate in this system.

5. Methylene blue (20 μmol/1) inhibited bradykinin‐induced relaxations when infused over the rabbit aortae, and reduced those relaxations produced by glyceryl trinitrate. The effects of bradykinin, but not glyceryl trinitrate, were partially restored after removing methylene blue.

6. These data are consistent with the known effects of these compounds on the activity of NO, and on EDRF in isolated blood vessels.

7. The activity of EDRF (released by bradykinin) was compared directly with NO on strips of guinea‐pig trachea (de‐epithelialized) interposed in cascade between two rabbit aortae; all strips were precontracted with histamine and phenylephrine.

8. A submaximal dose of NO that matched the relaxation produced by EDRF on the uppermost aorta, caused relaxation of the trachea, but EDRF had no effect on this tissue. In addition, the NO‐induced relaxation of the lower aorta was greater than that produced by EDRF.

9. These data indicate that EDRF does not have identical biological activity to NO. EDRF could contain an NO moiety attached to a carrier molecule that is bound and stabilized in tracheal tissue.
SECONDARY SIGNALLING MECHANISMS IN ANGIOTENSIN II‐STIMULATED VASCULAR SMOOTH MUSCLE CELLS
Authors: Griendling Kathy K. , Berk Bradford C. , Socorro Lilian , Tsuda Terutaka , Delafontaine Patrick , Alexander R. Wayne
Published: June 2007

1. Activation of vascular smooth muscle by angiotensin II results in the generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG).

2. IP3 is responsible for mobilizing calcium from endoplasmic reticulum. This signal is transient, most likely serving to initiate calcium events leading to contraction, and is attenuated by activation of protein kinase C.

3. DG stimulates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. Accumulation of DG/activation of protein kinase C is sustained, and may be enhanced by concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II‐receptor complex.

4. Angiotensin II‐stimulated, phospholipase C‐mediated IP3 formation is also modulated by a pertussis toxin‐insensitive guanine nucleotide regulatory protein.

5. The GTP binding protein, movement of the receptor‐ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle cells to angiotensin II stimulation.
RELATIVE INHIBITORY POTENCY AND PLASMA DRUG LEVELS OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN THE RAT
Authors: Johnston C. I. , Cubela R. , Jackson B.
Published: June 2007

1. 125I‐351A, a tyrosyl derivative of the angiotensin converting enzyme (ACE) inhibitor lisinopril, was used as a radioligand, and radioinhibitor binding and displacement assays have been established.

2. The in vitro potency of a range of ACE inhibitors against rat ACE was determined using the radioinhibitor binding displacement assay.

3. The concentration of an ACE inhibitor needed to displace 50% of 125I‐351A bound to rat ACE (ID50) was closely correlated with the concentration needed to inhibit 50% of ACE enzymatic activity (IC50).

4. Radioinhibitor binding displacement assay was used to measure the plasma concentrations of lisinopril, cilazapril and perindopril in rat plasma

5. Plasma concentrations of lisinopril measured by radioimmunoassay were identical with that measured by radioinhibitor binding assays.
EFFECT OF ENALAPRIL TREATMENT ON PROGRESSION OF THE NEPHROTOXIC SERUM NEPHRITIS MODEL OF RENAL FAILURE IN THE RAT
Authors: Jackson B. , Debrevi L.
Published: June 2007

1. Nephrotoxic serum nephritis was induced immunologically in uninephrectomized Sprague‐Dawley rats (n= 24). One‐half were assigned randomly to treatment with enalapril (5 mg/kg per 24 h).

2. Untreated rats (n= 12) developed a progressive fall in creatinine clearance, a progressive rise in systolic blood pressure and marked proteinuria over a 6 week period. The mortality rate was 42% at 5 weeks and 66% at 6 weeks.

3. Enalapril‐treated rats (n= 12) had no significant reduction in systolic blood pressure, and a similar reduction in creatinine clearance to that in untreated rats. Mortality was 50% at 5 weeks, and 92% at 6 weeks.

4. Proteinuria but not the blood pressure rise was significantly reduced by enalapril treatment.

5. Converting enzyme inhibitors may have a specific role in the treatment of nephritic diseases.
COMPARATIVE NEUROANATOMY OF ANGIOTENSIN II RECEPTOR LOCALIZATION IN THE MAMMALIAN HYPOTHALAMUS
Authors: Allen A. M. , McKinley M. J. , Mendelsohn F. A. O.
Published: June 2007

1. The distribution of angiotensin II (AII) receptor binding sites in the hypothalamus of rat, rabbit, sheep and human was determined by in vitro auto‐radiography using 125I‐[Sar1, IIe8]‐AII as radioligand.

2. High receptor binding levels were observed in the continuum of tissue comprising the anterior wall of the third ventricle, including the subfornical organ, the median pre‐optic nucleus and the organum vasculosum of the lamina terminalis.

3. High levels of binding sites were also found in the paraventricular and supra‐optic nuclei, the median eminence and the arcuate nucleus.

4. These findings demonstrate sites in the hypothalamus of rat, rabbit, sheep and human where AII could exert its known actions on fluid and electrolyte balance, pituitary hormone release and cardiovascular function.