Role of lipoxygenase products in the effects of angiotensin II in the isolated aorta and perfused heart of the rat

The objective of this study was to determine whether arachidonate metabolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) significantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug). In the heart, the nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 μM) markedly suppressed the angiotensin II-induced decreases in coronary flow. NDGA (10 μM) inhibited both angiotensin II- and methoxamine- (reference drug) induced contractions in aortic rings with (in the presence of L-NAME) and without endothelium. In the heart, the leukotriene synthesis inhibitor MK-886 (0.3 μM) significantly reduced the maximal effects to angiotensin II, but the leukotriene antagonist FPL 55712 (0.1 and 0.3 μM) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases in coronary flow are in part mediated by Hpoxygenase products, which might be derived from the 5-Hpoxygenase pathway, but are probably not leukotrienes. Furthermore, endothelium independent Hpoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta

Cyclic-AMP mediated drugs: differential or global reduction of eicosanoid synthesis in the isolated rat lung?

In this study the question was addressed whether cAMP mediated drugs induce a differential reduction of branches of the arachidonic acid metabolism rather than a global reduction of eicosanoid synthesis. The isolated lungs of actively sensitized rats were employed to study prostaglandin and leukotriene release in the presence and absence of the cAMP mediated drugs theophylline, milrinone, sulmazole, isobutyl-methylxanthine and salbutamol. The release of eicosanoids as measured by RIA was predominantly basal and continuous, with a mild antigen induced stimulation only for TXB2 and the leukotrienes. All drugs reduced eicosanoid release globally. It is concluded that cAMP mediated drugs interfere with arachidonic acid metabolism at a site proximal to the branching into lipoxygenase and cyclo-oxygenase pathways

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Trauma - today and tomorrowNeutron therapy - clinical considerationsDon Craib's legacyHealth informatic

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ix, 165 p.; 21 cm

[Effects of synthetic IgE-mediated peptides and anti-IgE conjugatevaccines in the cardiovascular system of the rat.]

In anaphylactic reactions IgE-mediated effects on the pulmonary and cardiovascular system play a pivotal role. The sequence of amino acids of the chains of the IgE-antibody is known and decapeptides can be synthesized resembling that part of the chains which binds to the mast cells resulting in the release of histamine and leucotrienes. In theory these synthetic decapeptides can be used as the first step for the vaccine development. Another approach would be the construction of peptides with binding capacity but no stimulating activity resulting in the blocking of IgE-binding sites on the target cells. In this feasibility study pilot experiments were performed on the isolated heart of the (actively TNP-ovalbumin sensitized) rat with coronary flow as parameter. Although the pilot experiments indicated an approach leading to either effective peptide antagonists or vaccines it was foreseen that reaching this goal the demand on research capacity would be substantial. In defining priorities the final conclusion was reasched to end these experiments.RIV

[Extension of second messengers: phosphoinositolsystem. Final report on pilotexperiments.]

A pilot study was conducted in order to investigate the possibility to measure the IP3 (inositoltrisphosphate) content in cardiovascular tissue of the rat, by means of a radioimmunoassay. With the kit is was possible to obtain a linear standard calibration curve. In extracts of control- and 10 mM NaF stimulated aorta's and left ventricles it appeared that with the applied method the measurement of IP3 was unsuccessful. In contrast to the sample preparation method, the measurement assay is not problematic. It was decided not to continue further investigations.RIV

[Assay of beta-adrenergic bindingcharacteristics in human-and rat lymphocytes.]

Bindingcharacteristics of beta-adrenergic receptors were assayed in membranes of human-and rat lymphocytes using iodocyanopindolol (ICYP) as radioactive labelled ligand. The affinity constant (Kd) of ICYP for human and rat adrenergic receptors was respectively 8.5 and 16.5 pM. Total number of receptors (Bmax) in the species studied were respectively 70 and 160 fmole/mg protein.RIV

Een eenvoudige en gevoelige bepalingsmethode voor de stikstofoxide-metabolieten nitriet en nitraat in serum, bronchoalveolaire lavagevloeistof en cultuurmedia

NO (Stikstof mono-oxide) wordt door het NO-synthase uit L-arginine vrijgezet en vertegenwoordigt een belangrijke intra- en intercellulaire boodschapperfunctie. Binnen biologische systemen wordt het NO snel naar nitriet en nitraat geoxideerd. Het totale nitriet is te beschouwen als parameter voor NO-synthase activiteit en wordt gekwantificeerd met behulp van de lichtabsorbtie van het Griess-chromofoor bij 420 nm na reductie van nitraat naar nitriet met Klebsiella pneumoniae (BBD 900.990). Met deze methode kunnen secundaire NO-synthase producten op reproduceerbare wijze in sera en andere eiwitbevattende media, zoals bronchoalveolaire wasvloeistoffen en gekleurde kweekmedia met een detectielimiet van 0,3 muM bepaald worden.NO (nitric mono-oxide) released from L-arginine by NO-synthase represents an important intra- and intercellular messenger. Within biological systems NO is rapidly oxidized to nitrite and nitrate. Total nitrite regarded as parameter for NO-synthase activity is quantified using absorbance of the Griess chromophore at 420 nm after deproteination and reduction of nitrate to nitrite using Klebsiella pneumoniae (BBD 900.990). This method allows reproducible assay of secundary NO-synthase products in sera and other protein containing media like bronchoalveolar lavages and coloured culture media with a detection limit of 0.3 muM.RIV

Pharmacokinetic-pharmacodynamic modelling of oxprenolol in man using continuous non-invasive blood pressure monitoring

The relationship between the plasma concentration of oxprenolol and its haemodynamic effects during physical exercise was studied in 6 healthy volunteers, in whom BP and heart rate (HR) were continuously monitored by non-invasive techniques (Fin-A-Press-Tonometer) during repeated three-minute exercise periods for 8 h after treatment. Using the fitted pharmacokinetic curve, the drug effect was related to its plasma concentration using the Emax model. The mean EC50 for the relationship between drug concentration and heart rate during exercise (HRex) was 73.1 ng/ml, and for systolic blood pressure during exercise (SBPex) it was 112.7 ng/ml. Emax was 29.0% for HRex, and 33.2% for SBPex. There were no consistent differences between the parameters for the effects on HRex and SPBex. Thus, using a new, non-invasive technique for continuous measurement of blood pressure, the effect of a beta-adrenoceptor blocking drug on SBPex was described with similar accuracy as its effect on HRe