Prostaglandin endoperoxides IV. Effects on smooth muscle.
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Biomedical subjects
Publications and source records attributed to K Strandberg.
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The administration of egg albumin to rabbits sensitized to this antigen caused marked increases in the arterial concentration of lactate, glucose and glycerol, but no change in the arterial FFA level. Antigen administration had no effect in non-sensitized rabbits. Phentolamine (3 mg/kg) or propranolol (1 mg/kg) did not significantly alter the responses to egg albumin in sensitized rabbits. Noradrenaline or sympathetic nerve stimulation decreased blood flow but caused no significant change in lipolysis in rabbit epigastric adipose tissue in situ. It is therefore questionable if catecholamines are the major cause of the observed metabolic consequences of the anaphylactic reaction in the rabbit. These metabolic events, i.e. increased lactate levels, lipolysis, and reesterification of fatty acids, are similar to those reported during hemorrhagic or endotoxin shock in dogs, in spite of specied-differences and the difference in the genesis of the shock.
The incorporation of labelled phospholipid precursors, [Me-14C]-choline, L-[3(-14)C]-serine, [2(-14)C]-ethanolamine and [2(-3)H]-myoinositol into the phospholipids of isolated rat mast cells was studied. The label from the different precursors were found to be essentially associated with compounds with the t.1.c.-motility of the respective phospholipids. Whereas the incorporation of [Me(-14)c]-choline and L-[3(-14)C]-serine showed evidence of saturation the incorporation of [2(-14)C]-ethanolamine was linear with time (2 h) and it was not saturated by increasing the concentration from 0.07 mM to 2.07 mM. The incorporation of [2(-3)H]-myoinositol was stimulated by Ca2+ (1 mM) or Mg2+ (1 mM), while the incorporation of the other precursors was stimulated only in the presence of both Ca2+ and Mg2+ (1 mM). Antimycin A (1muM), an inhibitor of the respiratory chain, significantly ingibited the incorporation of [Me(-14)c]-choline, L-[3(-14)C]-serine and [2(-3)H]-myoinositol but not that of [2(-14)C]-ethanolamine. The experimental system used might be a useful model for studies on the turnover of membrane phospholipids during histamine release.
SRS, PGF2chi, and histamine were administered intravenously or as aerosols to artifically ventilated guinea-pigs in order to asses their capacity to affect tracheal insufflation pressure measured by means of Konzett-Rössler technique, Independently of route of administration all three compounds increased tracheal insufflation pressure, SRS being the most potent one. Bilateral cervical vagotomy did not alter the effect. Relative to histamine SRS and PGF2chi were considerably more active by aerosol administration than by intranvenous injection. The aerosols had little or no effect on systemic blood pressure. On intravenous injection, histamine decreased and SRS and PGF2chi increased arterial blood pressure in a dose-dependent fashion. The airway effects of histamine were correlated to those on blood pressure whereas with SRS and PGF2chi this was not seen when the blood pressure effects were marked. Preadministration of adrenaline or isoprenaline as aerosols antagonized the increase in insufflation pressure, but not the effects on blood pressure, produced by intravenously injected histamine or PGF2chi. It is concluded that SRS, PGF2chi and histamine on intravenous or aerosol adminstration increase tracheal insufflation pressure in the guinea-pig mainly by an action on airway tone. The data emphasize that SRS is a potent bronchoconstricting agent, possibly of pathophysiological significance in guinea-pig anaphylaxis.
The effects of 2 prostaglandin synthetase inhibitors, indomethacin and eicosa-5,8,11,14-tetraynoic acid (ETA) and of the prostaglandin antagonist, polyphloretin phosphate (PPP), on the tone of the isolated human umbilical artery and on the responses of this preparation to 5-hydroxytryptamine (5-HG) and prostaglandin F2alpha (PGF2alpha) were investigated. Indomethacin (8 mug/ml), ETA (5 mug/ml) or PPP (40 mug/ml) reduced the tone of human umbilical arteries but had no influence on the responses to 5-HT. In these concentrations ETA and PPP but not indomethacin antagonized the action of PGF2alpha. When the concentration of indomethacin or PPP was increased 5-fold both 5-HT- and PGF2alpha-induced contractions were antagonized indicating a non-specific inhibition at these concentration levels. A 10-fold increase in the concentration of ETA had no antagonizing action on 5-HT-induced contractions suggesting a more selective inhibition of the PGF2alpha action than displayed by the other compounds. The effects on the tone of the human umbilical artery of the compounds studied might reflect inhibition of prostaglandin biosynthesis and/or antagonism of the action of formed prostaglandins. The findings are compatible with the view that intramural synthesis of prostaglandins contributes to the maintenance of the tone of the isolated human umbilical artery.
Derivatives of phloretin (25-1,000 mug/ml) among them polyphloretin phosphate (PPP), inhibited in a dose-dependent manner anaphylactic (birch pollen or horse dander) histamine release from human lung tissue passively sensitized with reaginic serum. Pretreatment with PPP of lung tissue sensitized both to birch pollen and horse dander counteracted to a similar extent the release of histamine induced by either allergen administered in sequence. The phloretin derivatives also antagonized the constrictor action of prostaglandin F2alpha on isolated human bronchi at concentrations which did not impair the responses to histamine. The low and high molecular weight derivatives of phloretin were comparably active on a weight basis in both experimental systems.
Prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) were found to be equipotent contractors of the isolated human umbilical artery (HUA) in the concentration range 0.2-40 mug/ml. Prostaglandin E1 (PGE1) relaxed HUA at 0.1-3.0 mug/ml, whereas at 10-50 mug/ml contraction occurred. PGE2 was significantly more potent at a PO2 of 102 mmHg than at 27, 48 and above 400 mmHg. An increase in PO2 per se (27- greater than 400 mmHg) resulted occasionally in minor increases in the tone of the HUA. Such effects of oxygen had a lag period of 10-15 min. It is suggested that an increased formation of prostaglandins in the umbilical artery at birth is a more likely cause of the closure of the vessel than an increase in PO2.
The tracheobronchial deposition of inhaled 99mTc tagged teflon particles of 6 mum (specific density 2g/cm3) was determined in rabbits by comparing the particle content in free dissected parts of the tracheobronchial tree with that in the whole lung. There was a singificantly larger deposition of particles in the proximal parts of the airways in rabbits exposed to an aerosol of the bronchoconstrictor compound carbachol than in control rabbits exposed to distilled water alone. The resistance to insufflation of a constant volume of air increased during the exposure to the carbachol aerosol, indicating bronchoconstriction. There was reproducible interindividual differences in bronchoconstrictor response to the carbachol aerosol. They were attributed to interindividual differences either in deposition of carbachol or in bronchial muscle sensitivity to carbachol. It is concluded that bronchoconstriction might serve as a defensive measure in causing a more proximal deposition of inhaled particles.
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