Search PubMed⌕ Search

Biomedical subjects

J B Warren

Publications and source records attributed to J B Warren.

At least 55 records · Page 3Linked to original sources
PubMed1991

Production of endothelin by vascular smooth muscle cells.

Endothelin (ET) production by cultured vascular smooth muscle cells isolated from rat and rabbit aortae was measured by a specific radioimmunoassay. Vascular smooth muscle cells released ET at a rate of 0.6 (range of 0.1-1) fmol/10(5) cells/24 h compared to 45 (range of 10-80) fmol/10(5) cells/h for endothelial cells. ET immunoreactivity was confirmed as ET-1 by fast protein liquid chromatography. Calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) suppressed basal release of ET by 24-66% from both rat and rabbit vascular smooth muscle. Forskolin and dibutryl-cAMP similarly suppressed ET release by 33-86%, suggesting that increased intracellular cAMP may account for the mechanism of action of CGRP and VIP. In contrast, CGRP and VIP did not have any effect on ET release from endothelial cells. The characteristics and regulation of ET binding sites on vascular smooth muscle cells were measured using [125I]ET-1 as the radioligand. Pretreatment with CGRP, VIP, forskolin, and dibutryl-cAMP increased the ET receptor density on both smooth muscle cell types. The low level production of ET-1 by vascular smooth muscle cells may have an important autocrine function and may be under regulation of neuropeptides localized to perivascular nerves.

Actins↗
PubMed1990

Vascular smooth muscle influences the release of endothelium-derived relaxing factor.

Conditioned medium was collected from vascular smooth-muscle cells grown in culture to determine if these cells synthesize vasoactive substances. The medium caused a short-acting endothelium-independent constriction of rat aorta, followed by a prolonged, endothelium-dependent relaxation. This relaxation was mediated through the release of endothelium-derived relaxing factor (EDRF) as it was abolished by the addition of methylene blue (5 x 10(-6) M), haemoglobin (10(-6) M) or methyl arginine, but was not affected by indomethacin (10(-5) M). Smooth-muscle medium stimulated the production of EDRF from both rat and rabbit thoracic aortic rings as well as from cultured bovine pulmonary artery endothelial cells. The prolonged stimulation of EDRF by smooth-muscle medium was not mimicked by known physiological stimuli to EDRF release; EDRF-stimulating activity was not affected when smooth-muscle cells were grown in the presence of indomethacin (10(-5) M), although serum in the medium was required. The EDRF-stimulating substance(s) in the smooth-muscle medium was heat stable and associated with a high molecular mass (30,000 greater than Mr greater than 3500) water-soluble species that is as yet unidentified.

Animals↗
PubMed1990

Nitric oxide is inactivated by the bacterial pigment pyocyanin.

Pyocyanin is a phenazine pigment produced by the bacterium Pseudomonas aeruginosa and found in human lung secretions. Micromolar concentrations of pyocyanin inhibited the bioactivity of endothelium-derived relaxing factor (EDRF) generated from bovine pulmonary-artery endothelium in response to bradykinin. This inhibition was reversed by perfusing the EDRF-bioassay system with pyocyanin-free buffer for 15 min, but persisted in the presence of superoxide dismutase (20 units/ml). When nitric oxide, the major component of EDRF, was passed into an aqueous solution of pyocyanin in the absence of O2, a rapid colour change occurred from blue to pink; m.s. analysis of the products showed that the pyocyanin had been converted into a nitrosylated species.

Animals↗
PubMed1990

Rapid tolerance to the hypotensive effects of glyceryl trinitrate in the rat: prevention by N-acetyl-L- but not N-acetyl-D-cysteine.

1. A new model of tolerance to the hypotensive effect of organic nitrates has been developed in the rat. 2. The fall in mean arterial pressure (MAP) in response to bolus doses of sodium nitroprusside (NP) (4 micrograms kg-1) and glyceryl trinitrate (GTN) (10 micrograms kg-1) was recorded both before and after a 60 min infusion of either 0.9% saline, NP (20 micrograms kg-1 min-1) or GTN (40 micrograms kg-1 min-1). 3. The hypotensive effects of NP or GTN were unchanged following saline infusion, but were reduced in both cases by approximately 40% following the infusion of NP. 4. Infusion of GTN for 60 min virtually abolished the hypotensive effect of a GTN bolus (i.e. nitrate tolerance), whilst the effect of a NP bolus was reduced only to a similar extent (30%) as after an infusion of NP. This latter effect is attributed to a degree of non-specific cross-tolerance between GTN and NP. 5. Co-treatment of a group of rats with N-acetyl-L-cysteine (L-NAC) prevented the development of nitrate tolerance, confirming the role of thiols in this phenomenon, whereas N-acetyl-D-cysteine (D-NAC) did not. 6. The stereospecificity in the effect of NAC in preventing this specific tolerance to GTN suggests that the interaction between GTN and NAC and/or cysteine involves an enzyme-dependent step. 7. NAC was unable to prevent the non-specific cross-tolerance to NP which followed infusion of GTN, suggesting that the mechanism does not directly involve NAC and/or cysteine.

Acetylcysteine↗
PubMed1990

Inhibition of nitric oxide synthesis potentiates hypoxic vasoconstriction in isolated rat lungs.

We have investigated the influence of endogenous nitric oxide (NO) on the vascular resistance of isolated rat lungs by inhibiting its synthesis with the false substrate N-monomethyl-L-arginine (L-NMMA). When perfused with blood at constant flow the addition of L-NMMA (10(-3) M) did not affect pulmonary arterial pressure in hyperoxia but did increase the response to hypoxia (PO2 25-35 mmHg) by 2.5 +/- 0.2 fold (mean +/- S.E.M.). The effect of L-NMMA was reversed by 3 x 10(-3) M-L-arginine, the true substrate for NO synthesis. Thus NO is an important pulmonary vasodilator but hypoxic vasoconstriction does not result from a reduction of its background release.

Animals↗
PubMed1989

Lymphopenia in primary degenerative dementia.

The central nervous and immune systems share a number of common properties, e.g. neurotransmitter receptors. In contrast to age matched healthy and/or hypertensive controls, the total lymphocyte count in 25 carefully diagnosed and staged patients with primary degenerative dementia were significantly reduced and also correlated with the severity of their dementia. Subjects' age, age of dementia onset, or duration of illness were unrelated. Total leukocyte counts were similar between groups. Nutritional status, ACTH, or plasma cortisol in dementia cohort were also not explanatory of their lymphopenia. These results are potentially significant in light of an immune hypothesis for primary degenerative dementia: Alzheimer's type and/or that population's high concomitant risk of infection.

Adrenocorticotropic Hormone↗
PubMed1989

Absorption edge imaging of bacterial endospores with synchrotron radiation.

This article describes a new method of viewing biological specimens by taking advantage of the absorptive characteristics of monochromatic X-rays above and below the absorption edge of a specific element. Bacterial endospores were imaged before and after treatment with an experimental vanadium-containing sporocide using monochromatic synchrotron radiation at the nitrogen absorption edge, and above and below the vanadium LIII absorption edge. This morphological study demonstrates a rapid, easy-to-use method of soft X-ray absorption edge imaging that can be used by the biologist to obtain morphological and elemental information that is not readily accessible using conventional microscopic and analytic techniques.

Absorption↗
PubMed1989

Assessment of MK-912, an alpha 2-adrenoceptor antagonist, with use of intravenous clonidine.

MK-912, a new alpha 2-adrenoceptor antagonist, was assessed in six volunteers by use of antagonism of the effects of intravenous clonidine as the main index of response. Subjects received single doses of either 0.2 or 2 mg of orally administered MK-912 or placebo in a randomized, double-blind, balanced, crossover design. Clonidine was infused intravenously over 10 minutes, 1 hour after dosing, and observations were made for 8 hours. The 2 mg dose of MK-912 significantly inhibited the clonidine-induced hypotension, bradycardia, xerostomia, and increase in plasma glucose concentrations that were observed during the placebo treatment period (p less than 0.05). The peak elevation in plasma growth hormone that was produced by clonidine on the day the placebo was given was inhibited an average of 87% by the 2 mg dose of MK-912 (p less than 0.01). Although there was a trend toward antagonism of clonidine by the 0.2 mg dose of MK-912, statistically significant differences from placebo were not consistently demonstrated for most parameters. However, a mean 59% inhibition of the clonidine-induced peak elevation of plasma growth hormone was observed (p less than 0.05). Oral MK-912 almost completely inhibits the effect of 200 micrograms of intravenous clonidine in human subjects, which is consistent with its role as a potent alpha 2-antagonist over the dose range of 0.2 to 2.0 mg.

Adrenergic alpha-Antagonists↗
PubMed1989

Pulmonary endothelium-derived relaxing factor is impaired in hypoxia.

1. The vasoconstrictor and vasodilator activity of cultured bovine pulmonary artery endothelial cells was measured to determine how exposure to different partial pressures of O2 [PO2 142,42 and 15 mmHg (18.9, 5.6 and 2 kPa)] affects the production of endothelial-derived relaxing and constrictor factors. 2. A de-endothelialized rat aortic ring [maintained at a PO2 of 142 mmHg (18.9 kPa)] was used to bioassay the effluent from a perfused column of bovine endothelial cells grown on microcarrier beads. The endothelial cells were stimulated by 10(-7) mol/l bradykinin given for 1 min at 12 min intervals. 3. At the start, middle and end of the experiment the bovine endothelial cells were exposed to a PO2 of 142 mmHg (18.9 kPa) and when stimulated by bradykinin the perfusate caused respectively a 70 +/- 4%, 63 +/- 6% and 63 +/- 6% (mean +/- SEM) relaxation of an aortic ring which had been pre-contracted by 10(-6) mol/l phenylephrine. At a PO2 of 42 mmHg (5.6 kPa) the relaxation induced by the cells was not significantly altered, but this tailed to zero after 26-38 min exposure of the cells to a PO2 of 15 mmHg (2 kPa). 4. These responses were unaltered by the presence of 10(-5) mol/l indomethacin, suggesting that prostacyclin is not a significant vasodilator in this system. 5. Reduced production of endothelium-derived relaxant factor rather than production of a constrictor factor, or a direct effect on the smooth muscle, may be involved in pulmonary hypoxic vasoconstriction.

Animals↗
PubMed1989

Importance of beta 2-adrenoceptor stimulation in the suppression of intradermal antigen challenge by adrenaline.

1. Seven atopic subjects received two injections of antigen and one of saline intradermally in the back on each of 4 separate days. They were pretreated with four different drug combinations: (a) adrenaline 0.3 mg subcutaneously over the deltoid muscle (b) subcutaneous adrenaline preceded by 5 mg of the specific beta 2-adrenoceptor antagonist ICI 118,551 orally (c) 8 mg of salbutamol orally (d) placebo. Tablets were given 2 h before and subcutaneous injections 15 min before the intradermal injections of saline and antigen. 2. The median flare response to intradermal low dose antigen and high dose antigen after pretreatment with adrenaline was 4% and 49% of the response seen following pretreatment with placebo (P less than 0.001). When adrenaline was preceded by ICI-118,551, the corresponding median flare responses were 2% and 44% (P less than 0.001) of the placebo response. The flare response after pretreatment with salbutamol was not significantly different from placebo. 3. Adrenaline suppressed the median weal response to the higher dose of antigen to 52% of the response after pretreatment with placebo (P less than 0.05). This suppression by adrenaline was blocked by pretreatment with ICI 118,551. The median weal response after the highest dose of antigen was suppressed by salbutamol to 66% of the response seen after placebo, although this was not significant even when a further three subjects were studied with either salbutamol or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

The importance of bradykinin and histamine in the skin response to antigen.

On three separate occasions 12 atopic subjects were injected intradermally with two doses of antigen and one of saline as control. Pretreatment with terfenadine 60 mg orally significantly inhibited the flare response to both the lower dose of antigen and to saline (P less than 0.05). Ingestion of enalapril 5 mg orally 3 h before increased the flare response to both doses of antigen. Neither enalapril nor terfenadine affected the weal response when compared with placebo. Both endogenous histamine and bradykinin appear to be released during the intradermal flare response but are not important in the weal reaction to antigen.

Adult↗
PubMed1988

Systemic adrenaline attenuates skin response to antigen and histamine.

Six atopic subjects received either adrenaline (0.3 ml of 1 mg/ml), subcutaneously over the deltoid muscle, or saline on 2 separate days. After 10 min, histamine and antigen were injected intradermally in the forearm. Adrenaline significantly inhibited the flare of histamine and both the flare and weal of antigen (P less than 0.05). This anti-allergic action of adrenaline occurred with a dose that we have previously shown produces plasma concentrations at the upper limit of the physiological range in resting normal subjects.

Adrenergic beta-Agonists↗
PubMed1988

The usefulness of alpha-adrenoceptor blockade in the treatment of hypertension.

The development of selective peripheral alpha 1-adrenoceptor antagonists such as prazosin has produced a valuable class of antihypertensive agents. Side effects of fluid retention and reflex sympathetic stimulation usually limit these agents to third-line therapy but their combination with a beta-receptor antagonist and a diuretic provides a powerful regimen. Alpha-adrenoceptor antagonists are useful in patients with conditions such as gout, diabetes or bronchospasm which preclude the use of other agents. Although many new drugs are being developed, little information is available yet on the long-term outcome of therapy with this class of drugs for patients with hypertension.

Adrenergic alpha-Antagonists↗
PubMed1987

Sustained-release diltiazem compared with atenolol monotherapy for mild to moderate systemic hypertension.

The daily administration of 240 to 360 mg of diltiazem lowered blood pressure in a dose-related pattern similar to that seen in patients taking a daily dosage of 50 to 100 mg of atenolol. Sustained-release diltiazem was administered twice daily and atenolol once. Goal blood pressure was defined as less than 90 mm Hg or a reduction of greater than or equal to 10 mm Hg for patients with baseline pressures of 95 to 99 mm Hg in the supine position and was achieved in 60% of diltiazem-treated and 63% of atenolol-treated patients. The mean diltiazem dosage at the end of the study was 329 mg daily; for atenolol it was 80 mg daily. Adverse reactions considered possibly or probably drug related were reported by 26% of diltiazem patients and 38% of atenolol patients. Although both drugs were associated with a slower heart rate, atenolol patients showed a significantly greater negative chronotropic effect. Diltiazem, in a sustained-release form taken twice daily, is as effective as atenolol as a sole antihypertensive agent. It has a favorable side-effect profile and may be a useful alternative antihypertensive medication compared with existing beta-blocker therapy with atenolol.

Atenolol↗
PubMed1987

Effect of enalapril on the skin response to bradykinin in man.

We tested the effect of oral enalapril on intradermal bradykinin to determine if kininase II inhibition occurs with therapeutic doses in vivo. Six normal male volunteers took either 5 mg enalapril orally or placebo on 2 days. Three hours later bradykinin was injected into the skin of the back in doses increasing from 10(-11) to 10(-9) M. Enalapril increased the bradykinin-induced wheal. Inhibition of kininase II may cause accumulation of endogenous bradykinin. This could be an important mechanism in the occasionally reported side effect of angioedema with the angiotensin converting enzyme (ACE) inhibiting group of drugs.

Administration, Oral↗
PubMed1987

Bradykinin-stimulated prostaglandin synthesis in conscious rabbits.

1 Bradykinin was infused intravenously into conscious rabbits to determine its effect on the concentration of prostaglandins in plasma. 6-Oxo-prostaglandin (PG) F1 alpha, the stable hydrolysis product of prostacyclin, and 13,14-dihydro-15-oxo-PGF2 alpha, a metabolite derived from PGE2 and PGF2 alpha, were measured by gas chromatography-electron capture mass spectrometry. 2 Incremental infusions of bradykinin (0.4-3.2 micrograms kg-1 min-1) increased plasma concentrations of both 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha. 3 Aspirin (10 mg kg-1, i.v.) inhibited bradykinin-stimulated 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha synthesis at 30 min and 6 h. At 24 h, the mean bradykinin-stimulated 13,14-dihydro-15-oxo-PGF2 alpha concentration was 66% of its original value, whilst 6-oxo-PGF1 alpha remained substantially inhibited. 4 The different rates of recovery of bradykinin-stimulated production of the two prostaglandins after inhibition by aspirin suggests that intravenous bradykinin stimulates prostacyclin and PGE2/PGF2 alpha production in distinct cell populations which synthesize cyclo-oxygenase at different rates.

Animals↗
PubMed1987

Airway caliber and the work of breathing in humans.

Mechanical work rate of breathing was measured in five normal subjects during voluntary eucapnic hyperventilation at rates of approximately 10, 20, 40, 60, and 80 l/min before and after inhalation of 1 mg of ipratropium bromide, an anticholinergic agent. Chest wall recoil pressure was measured over a range of lung volumes in each subject and was used as the reference pressure in the calculation of work rate. There was little change in elastic or resistive work rate at rest when vagal tone was reduced by ipratropium. The mean work at 40, 60, and 80 l/min was 8.9, 17.2, and 34.0 cmH2O.l-1.s before and 5.6, 12.4 and 25.8 cmH2O.l-1.s after ipratropium. This suggests that vagal tone significantly influences the work of breathing at high ventilatory rates, such as occur during strenuous exercise.

Adult↗