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Biomedical subjects

A G Herman

Publications and source records attributed to A G Herman.

At least 199 records · Page 11Linked to original sources
PubMed1984

Lung serotonin uptake kinetics from indicator-dilution and constant-infusion methods.

The kinetics of the pulmonary endothelial uptake of serotonin (5-HT) were evaluated in isolated dog lung lobes using three methods. In method A serotonin was infused at various constant rates to provide a range of capillary concentrations that included Km. The arterial and venous concentrations measured by high-performance liquid chromatography were then used to determine the effect of concentration on the rate of 5-HT uptake. In method B trace doses of 5-[3H]HT and a reference indicator (indocyanine green dye) were injected during each constant infusion of unlabeled 5-HT to provide a measure of unidirectional 5-HT uptake at each background concentration. In method C boluses containing different amounts of unlabeled 5-HT, along with the 5-[3H]HT and the dye, were injected such that each bolus resulted in a range of concentrations and provided a measure of the unidirectional uptake at each concentration. Each method provided the data needed to calculate the maximum uptake rate (Vmax) and the concentration at Vmax/2 (Km), assuming that the uptake kinetics can be represented by the Michaelis-Menten equation. However, the mathematical model underlying each method involved different assumptions about the returning flux of the 5-HT which entered the endothelial cell and the heterogeneity of vascular transit times. The results obtained, considered in light of the different assumptions involved, indicate that all three methods can provide reasonable estimates of the mass transfer kinetic constants if the constant infusions of 5-HT are of short duration and/or the boluses are adequately dispersed prior to reaching the capillary bed.

Animals↗
PubMed1984

Complement derived factors and prostacyclin formation by rabbit isolated peritoneum and cultured mesothelial cells.

Activation of rabbit or human serum complement led to the generation of factors which stimulated prostacyclin biosynthesis by isolated rabbit peritoneal tissue. Their formation was proportional to the degree of complement activation, measured as consumption of total hemolytic activity or immunoreactive C3. The stimulation of prostacyclin biosynthesis was mimicked by fragments obtained by trypsinisation of C3 (C3f) and C5 (C5f). Peritoneal macrophages, which could stimulate peritoneal prostacyclin biosynthesis through release of chemical mediators in response to C3f or C5f, were not essential, since the C3f and C5f also stimulated prostacyclin biosynthesis in monolayers of cultured mesothelial cells. Of the putative mediators, platelet activating factor (PAF) was inactive as a stimulator of peritoneal PGI2 biosynthesis. The finding that activated complement components stimulate prostacyclin biosynthesis forms an explanation for the endotoxin-induced rise in rabbit arterial blood levels of prostacyclin and may have wider implications for the understanding of inflammatory reactions.

Animals↗
PubMed1984

Prostacyclin biosynthesis and hypotension in relation to complement activation in rabbit endotoxic shock.

Intravenous endotoxin injection in rabbits led to complement activation, a biphasic hypotension and elevated arterial levels of prostacyclin and/or 6-oxo-prostaglandin F1 alpha. Primary hypotension and stimulation of prostacyclin biosynthesis were completely dependent on complement activation whereas the secondary changes of these parameters were partly complement dependent, as indicated by experiments with cobra venom factor pretreated rabbits. Prostacyclin, which was never detectable in arterial blood, contributed to the development of hypotension in rabbit endotoxic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

The metabolism of arachidonic and linoleic acid in rabbit peritoneal tissue: a short review.

The results obtained in the biotransformation studies demonstrate that lipoxygenase and PG-cyclo-oxygenase reactions represent major pathways in the metabolism of both arachidonic and linoleic acid in rabbit peritoneal tissue. Although the physiological significance of the hydroxy derivatives of arachidonic acid and linoleic acid is still unclear, it is tempting to assume that in tissues containing lipoxygenase activity, some of the effects ascribed to hydroxy arachidonates and their hydroperoxy precursors, e.g. inhibition of leukotriene and of PGI2 biosynthesis (16, 17) could for a great part be invoked by linoleic acid derivatives, as these products can be formed in larger quantities than the corresponding arachidonate derivatives.

Animals↗
PubMed1984

Influence of vitamin C on the metabolism of arachidonic acid and the development of aortic lesions during experimental atherosclerosis in rabbits.

Feeding rabbits a cholesterol-rich diet (0.3%) resulted in morphological changes and a decrease in the prostacyclin production by the aortic endothelium. Addition of vitamin C (0.1%) to the cholesterol-rich diet resulted in a decreased lipid infiltration and intimal thickening. Although there was a tendency to restore the prostacyclin output, vitamin C, in the amount administered, was unable to completely normalise the endothelial PGI2 production.

Animals↗
PubMed1983

Influence of endotoxin on arachidonate metabolism in isolated rabbit peritoneum.

The serous membranes of the rabbit peritoneal cavity are tissues in which cyclo-oxygenase and lipoxygenase pathways of arachidonate metabolism can be studied simultaneously. After elaboration of the optimum conditions, the metabolism of two concentrations of arachidonic acid (AA) was studied in the presence and absence of endotoxin lipopolysaccharide (LPS) from E. coli O127:B8 (0.1 and 1.0 mg/ml). LPS suppressed the formation of radiolabelled cyclo-oxygenase products (predominantly prostacyclin) at the lower concentration of exogenous AA (0.8 microM), but not at the higher substrate concentration (34.5 microM). The biosynthesis of lipoxygenase metabolites, i.e. monohydroxyeicosatetra-enoic acids (HETEs), was not influenced by LPS. These findings can be explained by an enhanced release of endogenous AA in the prostacyclin forming mesothelial cells in the presence of LPS. Measurements of the endogenous biosynthesis of prostacyclin supported this assumption.

Animals↗
PubMed1983

Relationship between prostacyclin biosynthesis and cyclic AMP in cultured rabbit mesothelial cells.

Calcium ionophore A23187 (10 microM) as well as thrombin (10 U/ml) stimulated the biosynthesis of prostacyclin in cultured rabbit mesothelial cells; in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (Mix, 1 mM) the cyclic AMP (cAMP) content was also elevated. Both effects were inhibited by indomethacin (28 microM). Exogenous prostacyclin elicited by itself a clear enhancement of intracellular cAMP. An increased cAMP content was also obtained with isoproterenol (10 microM), whose activity was antagonized by propranolol (10 microM). These two products however, had no effect on the prostacyclin release. In all these experiments, inhibition of phosphodiesterase with Mix, was necessary to obtain detectable cAMP levels. In the presence of Mix, the stimulation of prostacyclin production by A23187 and thrombin was significantly lower as compared to the stimulation in the absence of Mix. Our results suggest that increased prostacyclin biosynthesis results in adenylate cyclase stimulation. This rise in intracellular cAMP in the presence of Mix, is accompanied by a downward regulation of further prostacyclin production.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Activated complement and anaphylatoxins increase the in vitro production of prostacyclin by rabbit aorta endothelium.

The effect of activated human serum complement and highly purified anaphylatoxins on the production of prostacyclin (PGI2) by endothelium of the isolated rabbit aorta was investigated. The results indicated that complement activation with endotoxin (LPS) or cobra venom factor (CVF) led to the generation of principles that stimulated PGI2 formation. A similar effect was seen with tryptic cleavage products of complement factors C5 and C3, suggesting the possible involvement of anaphylatoxins. Indeed, on molar base purified porcine C5a and C5a des Arg were at least 1000 times more potent than other vasoactive inflammatory mediators, as stimulators of vascular PGI2 release. Therefore we suggest that complement-mediated stimulation of vascular PGI2 production contributes to the decreased peripheral vascular resistance during endotoxic shock in rabbits. We further propose that C5a-dependent stimulation of PGI2 formation may dilatate resistance vessels, thereby increasing local blood flow. Together with the vascular permeability effects of C5a, this may provide a local regulatory mechanism for histamine- and bradykinin-independent oedema formation during inflammatory reactions.

Anaphylatoxins↗
PubMed1983

Mechanism of complement-induced stimulation of prostacyclin production by isolated rabbit peritoneum.

The interaction between the complement system and prostaglandin synthesis has not thoroughly been explored, although both mediators are known to be involved in inflammatory reactions and endotoxic shock. When rabbit peritoneum, a rich source of prostacyclin forming activity was incubated in serum in which the complement system was activated (CVF, LPS, zymosan), the tissue produced significantly more PGI2, when compared with appropriate controls, indicating that by activation of the complement, factors were generated that stimulated PGI2 biosynthesis. Further results indicated that tryptic cleavage products of complement factor C3 and C5 also led to the appearance of PGI2 releasing principles with a molecular weight of about 7000-11000. The stimulation of PGI2 biosynthesis was explained by enhanced release of AA, and not due to increased activity of cyclo-oxygenase or PGI2 synthetase. Our results suggest that complement-derived products may promote the supply of prostaglandins at the site of inflammation.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Vitamin C increases the formation of prostacyclin by aortic rings from various species and neutralizes the inhibitory effect of 15-hydroperoxy-arachidonic acid.

Aortic rings from rats, rabbits and guinea-pigs produce different amounts of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), the stable breakdown product of prostacyclin, i.e. 2760 +/- 195, 160 +/- 10 and 87 +/- 17 pg 6-oxo-PGF1 alpha per mg wet weight in 30 min. Vitamin C enhances the production of 6-oxo-PGF1 alpha by the aortic tissue of these three species, independent of their basal release. This increase was only significant if vitamin C was present in the preincubation as well as in the incubation fluid. 15-Hydroperoxy-arachidonic acid inhibits the production of 6-oxo-PGF1 alpha (IC50:6 microM) and this inhibitory effect was completely neutralized by vitamin C. The increased production of 6-oxo-PGF1 alpha is not due to an increased release of the substrate arachidonic acid. It is suggested that vitamin C enhances the formation of 6-oxo-PGF1 alpha by protecting the cyclo-oxygenase and PGI-synthase.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effect of almitrine bismesylate on platelet aggregation and prostacyclin biosynthesis.

Almitrine bismesylate (1, 10 and 100 micrograms/ml) did not interfere with aggregation of rabbit blood platelets induced by arachidonic acid (100 micrograms/ml), ADP (10 microM) or collagen (10 micrograms/ml) in platelet rich plasma and did not augment the generation of prostacyclin by the rabbit aorta endothelium. Although almitrine bismesylate (2 mg/kg i.v.) increased the respiratory movements it did not stimulate prostacyclin biosynthesis in rabbits in vivo nor did it interfere with the ex vivo platelet aggregation induced by ADP or arachidonic acid and measured with the whole blood electronic aggregometer.

6-Ketoprostaglandin F1 alpha↗