bluuebunny/crossref_metadata_2025_split huggingface dataset:
ENHANCED CONTRACTION TO NORADRENALINE, SEROTONIN AND NERVE STIMULATION BUT NORMAL ENDOTHELIUM‐DERIVED RELAXING FACTOR RESPONSE IN SKIN SMALL ARTERIES IN HUMAN PRIMARY HYPERTENSION
Authors: Angus J. A. , Jennings G. L. , Sudhir K. 
Published: June 2007

SUMMARY1. We measured the reactivity of 2 mm long ring segments of human resistance arteries dissected from gluteal skin biopsies and mounted on wires in a Mulvany‐Halpern myograph for recording isometric force. Arteries were taken from eight normotensive (N) volunteers (average age 46 years, blood pressure 126/82 mmHg) and eight untreated hypertensives (H; average age 48 years, blood pressure 149/101 mmHg).2. In small diameter arteries (internal diameter < 500/μm), the cumulative concentration‐response curves to noradrenaline, serotonin and angiotensin II had a greater maximum by 72, 300 and 69%, respectively, in vessels from hypertensive patients than in those from normal volunteers. Nerve stimulation also caused a greater maximum contraction in hypertensive vessels (by 352%).3. Arteries from H and N patients contracted submaximally by the thromboxane mimetic U46619 were similarly sensitive to the endothelium‐dependent relaxing factor (EDRF) acetylcholine, indicating no difference in EDRF release or sensitivity.4. Morphological measurements of the ratio of wall thickness to lumen radius of the wire‐mounted vessels showed no significant difference between H and N vessels.5. In larger arteries (internal diameter > 500 μm), no response to acetylcholine was noted in either H or N arteries. The sensitivity to serotonin and angiotensin II was similar between these arteries but the EC50 to noradrenaline was less in H than in N arteries (ΔEC50= 0.61 ‐log mol/L).6. Subcutaneous resistance arteries with an internal diameter less than 500 μm from hypertensive patients show enhanced contractility to noradrenaline, serotonin and nerve stimulation despite a lack of detectable medial hypertrophy. These changes may be confined to the medium small arteries acting as pharmacological amplifiers in the circulation. We could not demonstrate a significant defect in neuronal uptake nor in endothelium‐derived relaxing factor in arteries from patients with essential hypertension.
COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PERINDOPRIL, CILAZAPRIL AND ENALAPRIL
Authors: Louis W. J. , Conway E. L. , Krum H. , Workman B. , Drummer O. H. , Lam W. , Phillips P. , Howes L. G. , Jackson B. 
Published: June 2007

SUMMARY1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose).2. Plasma levels of the active diacid compounds reached similar peaks after single dose administration of the drugs. However, perindoprilat levels persisted for 5 days whereas cilazaprilat levels were not detectable beyond 12 h.3. The higher levels of perindoprilat were associated with a greater inhibition of plasma angiotensin‐converting enzyme (ACE) activity in both acute and steady state studies.4. The potency of the active diacids in inhibiting plasma ACE activity was perindoprilat > cilazaprilat > enalaprilat.5. There was a close relationship between plasma concentration, ACE inhibition and blood pressure decrease. Although both cilazapril and perindopril administration reduced blood pressure in hypertensive subjects, only perindopril exerted 24 h blood pressure control at the doses used.
ANGIOTENSIN‐CONVERTING ENZYME INHIBITION AS FIRST‐LINE TREATMENT FOR HYPERTENSION
Authors: Thurston Herbert 
Published: June 2007

SUMMARY1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.2. A 4 week single‐blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side‐effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first‐line therapy for mild to moderate hypertension.
THE EFFECT OF SOME α2‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE
Authors: Ali B. H. , Bashir A. A. 
Published: June 2007

SUMMARY1. The effects of graded doses of the α2‐adrenoceptor agonists clonidine, tizanidine and BHT‐920, and the α2‐adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test.2. The agonists produced significant and dose‐dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT‐920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg).3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co‐administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg).4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT‐920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg).5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline‐treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT‐920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.
EFFECTS OF ANAESTHESIA ON THE REMOVAL FROM PLASMA OF INTRAVENOUSLY INJECTED CHYLOMICRON‐LIKE LIPID EMULSIONS IN RATS AND MICE
Authors: Mortimer Bok‐Cheng , Umeda Yoh , Elsegood Caryn L. , Redgrave Trevor G. 
Published: June 2007

SUMMARY1. In order to find an anaesthesia with minimum perturbation to the metabolism of chylomicrons, the effects of seven different anaesthetic agents on clearance from plasma of chylomicron‐like emulsions were compared.2. Avertin, urethane, fentanyl, and a ketamine/xylazine mixture all slowed the removal from plasma of emulsion triolein and cholesteryl oleate. The steroid anaesthetic althesin slowed the clearance of emulsion cholesteryl oleate without affecting the removal from plasma of emulsion triolein. Nembutal when injected intravenously at a hypnotic dose did not affect the clearance of emulsion triolein or cholesteryl oleate, whereas at the anaesthetic dose, nembutal slowed the clearance rate of both labelled lipids.3. Except for althesin, which did not affect the plasma clearance of triolein, fractional clearance rates of emulsion triolein and cholesteryl oleate calculated from blood samples taken during 12 min after injection were significantly slower in the anaesthetized groups compared with controls. However, with avertin, althesin, nembutal and ketamine/xylazine, amounts of radiolabelled triolein and cholesteryl oleate remaining in plasma 25 and 30 min after injection were comparable with the control. Radioactive lipids in plasma remained much higher in rats treated with urethane and fentanyl‐fluanisonium even 30 min after injection.4. Avertin was simple to administer and produced a suitable depth of anaesthesia for minor surgery, tail vein injections and blood sampling, whereas althesin and the ketamine/xylazine mixture required supplementary doses to maintain anaesthesia towards the end of the experiment. We concluded that anaesthesia is best avoided for studies of chylomicron clearance. Avertin is the preferred agent if anaesthesia must be used, for example in newborn rats or in mice.
EFFECTS OF VERAPAMIL AND DILTIAZEM ON DOPAMINE RELEASE IN THE CENTRAL NERVOUS SYSTEM OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Tsuda Kazushi , Tsuda Seiko , Goldstein Menek , Masuyama Yoshiaki 
Published: June 2007

SUMMARY1. The purpose of the present study was to investigate the effects of Ca2+‐antagonists (verapamil and diltiazem) on dopamine release in the central nervous system in hypertension.2. Striatal slices obtained from spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats were prelabelled with [3H]‐dopamine, and superfused with Krebs‐Ringer solution in vitro. The slices were stimulated electrically at a frequency of 1 Hz.3. Stimulation‐evoked release of [3H]‐dopamine from striatal slices was significantly decreased in SHR compared with WKY rats.4. Exposure of slices to verapamil and diltiazem significantly increased the stimulation‐evoked [3H]‐dopamine release. The facilitatory effects of the Ca2+‐antagonists on dopamine release were significantly greater in SHR than in WKY rats.5. Because central nervous system dopaminergic mechanisms appear to be depressor, the results suggest that the pronounced effects of verapamil and diltiazem on dopamine release in SHR might be involved in the central hypotensive mechanisms of the Ca2+‐antagonists.
EFFECTS OF NAFTIDROFURYL ON ISOLATED PERFUSED KIDNEYS OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Zhang B. L. , Liu K. L. , Sacquet J. , Wiernsperger N. , Benzoni D. , Sassard J. 
Published: June 2007

SUMMARY1. Experiments were designed to determine the effects of low concentrations (5–500 nmol/L) of naftidrofuryl, a 5‐hydroxytryptamine (5‐HT) antagonist, on renal functions and prostanoid synthesis responses to noradrenaline (NA) and 5‐HT. Isolated kidneys of 8 week old male spontaneously hypertensive rats were perfused at a constant flow rate in a single‐pass system.2. In baseline conditions, naftidrofuryl did not modify the renal vascular resistance and the glomerular filtration rate (GFR), although it elicited a significant but not dose‐dependent increase in the venous excretion of 6‐keto‐prostaglandin (PG) F1α and thromboxane (Tx)B2, the stable end‐products of PGI2 and TxA2, respectively.3. NA increased renal vascular resistance and GFR in a dose‐dependent manner and enhanced the venous excretion of 6‐keto‐PGF1α and TxB2. Naftidrofuryl significantly attenuated the effects of NA on renal vascular resistance, abolished those on GFR and enhanced, at the highest concentration (500 nmol/L) only, those on 6‐keto‐PGF1α excretion.4. 5‐HT increased renal vascular resistance but not GFR. It did not change the sodium excretion and the release of 6‐keto‐PGF1α and TxB2. Naftidrofuryl blunted the RVR response to 5‐HT without change in the prostanoid release. The inhibitory action of naftidrofuryl was not modified by indomethacin which, by itself, prevented the vasoconstrictor response to 5‐HT.5. It is concluded that, in isolated perfused kidneys of SHR, naftidrofuryl inhibits the contractile response to 5‐HT and NA; this effect is not dependent upon changes in synthesis of PGI2 or TxA2 and the vasoconstrictor effect of 5‐HT involves the release of a cyclooxygenase metabolite that differs from TXA2.
EFFECTS OF HIGH SALT INTAKE ON CONTROL OF HINDLIMB VASCULAR RESISTANCE BY ARTERIAL BROREFLEX AND VAGAL AFFERENTS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Hoka Sumio , Takeshita Akira , Yamamoto Kunihiko , Ito Naoya 
Published: June 2007

SUMMARY1. This study aimed to examine whether a high salt diet alters control of vascular resistance by arterial baroreflex and vagal afferents in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY).2. SHR and WKY aged 8 weeks were fed either high (8%) or normal salt (0.4%) diet for 4 weeks. Arterial baroreflex control of hindlimb vascular resistance was assessed by examining reflex‐induced vasodilation and vasoconstriction in response to phenylephrine and nitroprusside, respectively, in the constant‐flow perfused hindlimb of urethane‐anesthetized rats.3. Tonic influence of the cardiopulmonary vagal afferents was evaluated by examining the effects of vagotomy on hindlimb vascular resistance and on the gain of arterial baroreflex control of hindlimb vascular resistance.4. The gain of the arterial baroreflex control of hindlimb vascular resistance in response to both phenylephrine and nitroprusside were not significantly different between SHR receiving high and normal salt diets, and between WKY receiving high and normal salt diets.5. Vagotomy increased hindlimb vascular resistance in all four groups of rats. However the magnitude of the increase in hindlimb vascular resistance was less in SHR on a high salt diet than those in SHR on a normal salt diet but similar between the two groups of WKY. Vagotomy increased the slope of arterial baroreflex control of hindlimb vascular resistance in SHR receiving a normal salt diet and the two groups of WKY but not in SHR receiving a high salt diet.6. These results suggest that a high salt diet attenuates the inhibitory influence of vagal afferents on the control of vascular resistance in SHR but not in WKY, while the arterial baroreflex control of vascular resistance is preserved during high salt diet in both SHR and WKY.
PREVENTIVE EFFECT OF A NEW CALCIUM ANTAGONIST, MONATEPIL, ON DRUG‐INDUCED ISCHAEMIC ELECTROCARDIOGRAPHIC CHANGES IN RATS
Authors: Yamamoto Taku , Nakatsuji Katsuyoshi , Hosoki Kanoo , Karasawa Tadahiko 
Published: June 2007

SUMMARY1. The preventive effects of monatepil, a new calcium antagonist with α1‐adrenoceptor blocking activity, on ischaemic electrocardiographic changes in rat models of vasospastic angina were evaluated and compared with those of the existing calcium antagonists (diltiazem, verapamil, nicardipine and nifedipine).2. In order to assess the contribution of the α1‐adrenoceptor blocking action of monatepil to its anti‐vasospastic action, the anti‐ST depression effect of prazosin, an α1‐adrenoceptor blocker, was also examined.3. Monatepil given orally (3–30 mg/kg) inhibited vasopressin (0.2 IU/kg, i.v.)‐induced ST depression which is considered to indicate ischaemic electrocardiographic changes in a vasospastic angina. This effect of monatepil was more potent and long‐lasting than that of diltiazem, and was similar to that of verapamil and nicardipine. At a dose of 30 mg/kg, monatepil produced a significant inhibition, even at 7 h after administration.4. Monatepil given intravenously (0.3 mg/kg) exerted a significant inhibitory effect on methacholine (16 μg/kg, intracoronary arterial administration; i.c.a.)‐induced ST elevation which seems to be caused by coronary vasospasm. This effect was more potent or equipotent to those of the existing calcium antagonists.5. These results indicate that monatepil produces the preventive effect on the drug‐induced ischaemic electrocardiographic changes in rats and suggest that monatepil may have potential for the treatment of vasospastic angina.
BLOOD PRESSURE EFFECTS OF THROMBOXANE A2 BLOCKADE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Boussairi El Habib , Sacquet Joëlle , Benzoni Daniel , Sassard Jean 
Published: June 2007

SUMMARY1. The effects of CGS 22652, a thromboxane (Tx) A2 synthase inhibitor and TxA2 prostaglandin (PG) H2 receptor antagonist, on blood pressure (BP) were studied in conscious freely moving spontaneously hypertensive rats (SHR).2. Three groups of 13 male SHR were subcutaneously infused from 5 to 11 weeks of age via osmotic minipumps with CGS 22652 at doses of 5 (SHRa) or 10 (SHRb) mg/ kg per 24 h or with the vehicle only (SHRc). A fourth group (SHRd, n= 13) was orally treated from 3 to 11 weeks of age with CGS 22652 (30 mg/kg) given by gavage once a day.3. CGS 22652 dose‐dependently reduced the age‐related increase in systolic BP. The pressor response to noradrenaline (200 ng/kg, i.v.) but not to angiotensin I or II was slightly (P<0.05) diminished in 11 week old SHRb and SHRd compared to SHRc. Acute ganglionic blockade by trimethaphan (10 mg/kg, i.v.), as well as angiotensin converting enzyme inhibition by perindopril (2 mg/kg, i.v.) decreased BP to a similar extent in the four groups. After combined blockade of vasopressin receptors and of the autonomic nervous system and the administration of a direct vasodilator (hydralazine, 3 mg/kg, i.v.), the residual mean BP was identical in the four groups of rats.4. Chronic treatment with CGS 22652 dose‐dependently antagonized the TxA2 PGH2 receptors but did not modify the TxA2 synthesis. The urinary sodium excretion did not differ between groups.5. In conclusion, at the doses used, CGS 22652 given either orally or subcutaneously exhibited only TxA2/PGH2 receptor blocking properties in SHR. Chronic treatment modestly prevented the development of hypertension in SHR, probably through a decrease in the pressor effects of TxA2 and of noradrenaline.
THE EFFECTS OF PERTUSSIS TOXIN ON VASOCONSTRICTOR AND VASODILATOR AGENTS IN THE PITHED RAT MAY NOT BE AN INDICATOR OF G‐PROTEIN RECEPTOR COUPLING
Authors: Costa Mary , Majewski Henryk 
Published: June 2007

SUMMARY1. In the present study, rats were treated with pertussis toxin (8.4 μg, i.v.) to determine whether pertussis toxin‐sensitive G‐proteins were linked to receptors that mediate effects in the cardiovascular system.2. In the pithed rat the pressor responses to the α‐adrenoceptor agonists noradrenaline and (to a lesser extent) methoxamine were attenuated by pertussis toxin treatment; the tachycardia produced by noradrenaline was unaffected. The pressor response to serotonin was also attenuated by pertussis toxin treatment. These observations are consistent with known effects of pertussis toxin on these receptors.3. The vasodepressor responses to the muscarinic receptor agonist carbachol and to adenosine were reduced by pertussis toxin, suggesting that these events may have been mediated by pertussis toxin‐sensitive G‐proteins. However, the depressor responses to the β2‐adrenoceptor agonist salbutamol and to the receptor‐independent vasodilator drugs sodium nitroprusside and hydralazine were also reduced by pertussis toxin. These latter effects suggest that caution must be used in interpreting the effects of pertussis toxin since the mechanism of action of these drugs as elucidated in vitro is thought not to involve pertussis toxin‐sensitive G‐proteins.
IDENTIFICATION AND CHARACTERIZATION OF AN AMIDATING ENZYME IN OVINE HEART
Authors: Lew Rebecca A. , Smith A. Ian 
Published: June 2007

SUMMARY1. Levels of peptidylglycine α‐amidating mono‐oxygenase (PAM) activity were examined in sheep and rat heart. This enzyme is responsible for α‐amidation of a large number of peptide hormones, a modification essential for the bioactivity of these peptides.2. PAM activity was measured in membrane and soluble fractions of atrial and ventricular homogenates by monitoring the amidation of iodinated synthetic substrate ([125I]‐Ac‐Tyr‐Val‐Gly).3. PAM activity in both species resided almost exclusively in the atria rather than the ventricles, and similar levels of activity were found in left and right atria. Membrane‐associated activity was 50‐to 100‐fold greater than soluble activity in the sheep, yet was only five‐ to 10‐fold greater in the rat, indicating a larger proportion of soluble enzyme in the rat atrium.4. Similar apparent Km values were found for atrial membrane‐associated activity in both species (15.6 and 17.4 μmol/L for rat right and left atria, 16.7 and 15.6 μmol/L for sheep right and left atria); however, the maximum velocity (Vmax) levels were higher in the rat (40.5 and 43.9 pmol/μg per h vs 12.8 and 15.1 pmol/μg per h).5. Because expression of many peptides and processing enzymes can be regulated by steroid hormones, the possible effects of chronic glucocorticoid administration (1 mg dexamethasone i.m. twice daily for 10 days) on PAM levels were tested in four sheep, with four sheep receiving saline only as controls. There was no discernible effect of dexamethasone on either the distribution or the kinetics of PAM activity in the sheep heart.6. This study demonstrates the presence of high levels of predominantly membrane‐associated amidating activity in sheep atria, and the failure of glucocorticoid treatment to alter this activity. The presence of abundant atrial PAM activity suggests the production of an amidated peptide which has yet to be identified.
CORTISOL PRODUCTION BY ALDOSTERONE‐PRODUCING ADENOMASIN VITRO
Authors: Stowasser Michael , Tunny Terry J. , Klemm Shelley A. , Gordon Richard D. 
Published: June 2007

SUMMARY1.In vitroshort‐term production of cortisol by dispersed tumour and non‐tumorous adrenal cortical cells was measured with and without added angiotensin II (AII) or adrenocorticotrophin (ACTH) in adrenals removed from five patients with primary aldosteronism.2. Aldosterone‐producing adenomas (APA) were classified as angiotensin responsive (AII‐R) or angiotensin unresponsive (AII‐U) based on pre‐operative behaviourin vivo.3. Cortisol was produced by both tumour and cortexin vitrowithout stimulation, and significantly more cortisol was generated by the cortex.4. Addition of AII significantly increased cortisol production by both tumour and cortex to an equal extent.5. Addition of ACTH also significantly increased cortisol production by both tumour and cortex, but tumours were more responsive than cortex. The response to ACTH exceeded the response to angiotensin in both tumour and cortex.6. There was no obvious difference between AII‐R and AII‐U APA in terms of cortisol production.
DETECTION OF RENIN mRNA IN ALDOSTERONE‐PRODUCING ADENOMAS BY POLYMERASE CHAIN REACTION
Authors: Klemm Shelley , Pinet Florence , Rioual‐Caroff Nathalie , Tunny Terry , Corvol Pierre , Gordon Richard 
Published: June 2007

SUMMARY1. Ribonucleic acid (RNA) was extracted from two normal human adrenal cortices and from five aldosterone‐producing adenomas (APA).2. The five APA could be categorized, on the basis of in vivo aldosterone responsiveness to angiotensin infusion and upright posture, into two APA responsive to both stimuli, two responsive only to angiotensin infusion, and one unresponsive to either stimulus.3. RNA was reverse transcribed and coamplified by polymerase chain reaction (PCR) with an internal standard of renin complementary DNA (cDNA) containing a 60 base pair insertion. Renin mRNA in the APA was compared with normal adrenals.4. Renin mRNA was greater than normal in the two APA responsive to both stimuli and less than, or similar to normal, in the two APA responsive only to angiotensin infusion. Renin mRNA was also less than, or similar to normal, in the APA unresponsive to either stimulus.5. These findings support a possible role for adrenal renin in the development and biochemical behaviour of angiotensin‐responsive APA.