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Biomedical subjects

A Wennmalm

Publications and source records attributed to A Wennmalm.

At least 163 records · Page 9Linked to original sources
PubMed1978

Prostaglandin-mediated inhibition of noradrenaline release: IV. Prostaglandin synthesis is stimulated by myocardial adrenoceptors differing from the alpha- and beta-type.

The release of prostaglandin E elicited by sympathomimetic amines was studied in the isolated rabbit heart. The hearts were prepared according to Langendorff, with conventional recording of stroke frequency and contractile force. Assays were made of the outflow of PGE during exposition to equimolar concentrations of methoxamine, noradrenaline, adrenaline and isoprenaline, in the absence and in the presence of phentolamine or propranolol. Noradrenaline caused an almost four-fold increase in the basal outflow of PGE from the heart, while methoxamine (an alpha-adrenoceptor agonist) and isoprenaline (a beta-adrenoceptor agonist) were both ineffective in this respect. Thus, the PGE-releasing capacity of the drugs was not correlated to their ability to activate alpha- or or beta-adrenoceptors. Furthermore, no relation was obtained between the PGE release induced by the drugs and the increase in heart rate and contractile force elicited by them. It is suggested that sympathomimetic drugs trigger PGE synthesis and release in the rabbit myocardium following activation of a hitherto unobserved adrenoceptive mechanism, optimally stimulated by NA.

Animals↗
PubMed1977

Transmitter release and adrenergic mechanical responses in the heart: effect of papaverine and imidazole.

Chronotropic and inotropic responses were elicited in isolated rabbit hearts by stimulation of the sympathetic nerves or by infusion of noradrenaline or adrenaline and the effects of papaverine and imidazole (10(-7)-10(-6) M) on these responses were studied. The outflow of noradrenaline induced by sympathetic nerve stimulation was assayed in the absence and in the presence of papaverine and imidazole (10(-7)-5 X 10(-7) M). Papaverine increased the outflow of transmitter during nerve stimulation by 45% and potentiated both the chronotropic and inotropic responses induced by nerve stimulation and those induced by infusion of catecholamines. Imidazole inhibited the outflow of transmitter during nerve stimulation by 33%. The data indicate that the "second messenger" cyclic AMP is active in more than one step in adrenergic neurotransmission and receptor activation in the heart. Furthermore, tissue cyclic AMP seems to be involved not only in the inotropy induced by circulating catecholamines but also in the more "physiological" inotropy elicited by sympathetic nerve stimulation.

Animals↗
PubMed1977

Nicotine stimulates prostaglandin formation in the rabbit heart.

Rabbit isolated hearts were perfused according to Langendorff with Tyrode solution. Prostaglandin-like substances (PLS) in the effluent were purified and assayed on the rat stomach strip Noradrenaline (NA) in the effluent was assayed fluorimetrically. 2 Infusion of nicotine (1 muM-50 muM) caused a dose-dependent, brief increase, from 1.2+/-0.4 to maximally 8.3+/-2.1 ng/min, in the outflow of PLS from the heart. The increase was abolished by pretreatment of the heart with indomethacin. 3 Activation of nicotinic receptors in the heart with acetylcholine (ACh, 200 muM) in the presence of atropine (1 muM) also elicited an increase in the release of PLS. This release was smaller than that caused by nicotine. 4 Nicotine (50 muM) and ACh (200 muM) in the presence of atropine (1 muM) each caused a pronounced but brief release of NA into the effluent. There was no evident correlation between the ability of the drugs to cause release of PLS on the one hand, and NA on the other. 5 It is concluded that nicotine acts as a direct stimulus for the synthesis of prostaglandins in the rabbit heart.

Acetylcholine↗
PubMed1977

Differentiation of vasoconstrictor sensitivity caused by prostaglandin E in peripheral vascular beds of the rabbit.

The increase in perfusion pressure in the rabbit ear, hindleg and mesentery caused by close intra-arterial injection of noradrenaline (NA), and the contractile response to NA of the rabbit aortic strip were investigated with respect to their sentitivity to prostaglandin E1 (PGE1) and to the prostaglandin synthesis inhibitor indomethacin. PGE1 (100-200 ng) potentiated the increases in perfusion pressure caused by NA in the perfused hindleg and mesentery, and the contractile response to NA of the aortic strip by 25-80%, but inhibited the increase in perfusion pressure by NA in the perfused ear by 35-100%. Indomethacin (3-5 X 10(-5) M) significantly decreased the pressor responses to NA in the hindleg (by 45%) and mesentery (by 55%). This inhibitory effect by indomethacin was completely reversed by PGE1. The responses to NA in the aortic strip and the perfused ear were unaffected by indomethacin. It is concluded that the process of vasoconstriction in the vascular beds of the rabbit displays qualitative differences concerning its sensitivity to added PGE1. Furthermore, the decreased pressor responses to NA observed in some of the rabbit vascular beds after indomethacin indicate that the sensitivity to NA in these tissues in fact is increased by endogenous prostaglandin-like substances (PLS). The current results thus suggest that endogenous PLS may regulate, at a local level, the vasoconstrictor sensitivity in the rabbit systemicresistance vessels.

Animals↗
PubMed1976

Prostaglandin-mediated inhibition of noradrenaline release: its resistance to variations in rate of prostaglandine synthesis.

Isolated rabbit hearts were perfused according to Langendorff. The bilateral sympathetic nerve supply to the organ was stimulated at intervals, and the overflow of noradrenaline and of prostaglandins of the E series in the effluent was assayed, using fluorimetric and bioassay methods, respectively. The synthesis of prostaglandins in the organ was stimulated, either by perfusing the heart at a low pO2, or by infusing nicotinic acid. Hypoxia increased the coronary flow, provided the prostaglandin synthesis was not inhibited, probably as a consequence of hypoxia stimulation was however, unaffected by hypoxia. Nicotinic acid also stimulated prostaglandin formation, doubling the overflow of the lipid in response to nerve stimulation. In this series, too, the release of NA induced by nerve stimulation was unaffected by stimulation of prostaglandin synthesis. It is concluded that local variations in the rate of prostaglandin synthesis are unable to change the degree to which the release of sympathetic neurotransmitter is inhibited. Furthermore, it is suggested that the prostaglandin synthesis in rabbit heart takes place in compartments, separated functionally or morphologically.

Animals↗
PubMed1976

Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.

1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm. 2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1-25 mg/kg body weight) was administered. 3. Following 5 min of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Indomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml./100 ml. tissue before, and 13 ml./100 ml. tissue after administration of indomethacin. 4. During sustained isometric forearm contraction, and following isometric and dynamic forearm muscle activity, a moderate hyperaemia was observed. This was significantly diminished when indomethacin had been administered, although not to the same extent as the reactive hyperaemia. The total hyperaemia in the absence and presence of indomethacin was 113 and 77 ml./100 ml. tissue, respectively, in connexion with isometric contraction and 206 and 120 ml./100 ml. tissue, respectively, following dynamic work. 5. The venous concentration of PLS was very low at rest. A significantly increased concentration was observed after ischaemia. This increased release of PLS was entirely suppressed by indomethacin. With the present assay method, muscular activity elicited no detectable change in the venous concentration of PLS. 6. It is concluded that reactive hyperaemia depends to a considerable extent on an intact PGE synthesis. It is furthermore suggested that endogenous PGE may contribute to the functional hyperaemia that appears during and after muscle activity.

Forearm↗
PubMed1975

Turnover of a prostaglandin precursor, arachidonic acid, in rheumatoid arthritis.

The plasma concentration and the turnover of free arachidonic and oleic acids were determined in patients with rheumatoid arthritis and in control subjects. The plasma level of free arachidonic acid, but not of oleic acid, was significantly decreased in male rheumatoid patients. Female patients did not differ from healthy subjects in this respect. Following treatment with indomethacin, a significant increase in the plasma concentration of free arachidonic acid was observed in rheumatoid patients of both sexes. It is suggested that the findings in the rheumatoid patients reflect a partial exhaustion of the pool of arachidonic acid serving as precursor in the synthesis of prostaglandin.

Adult↗
PubMed1975

Turnover of plasma free arachidonic and oleic acids in men and women.

The turnover of plasma free arachidonic and oleic acids was determined in healthy men and women. The plasma pool of arachidonic acid in the men was 75 per cent higher than in the women. The fractional turnover of arachidonate was 0.80 +/- 0.04 min(-1) in the women and 0.47 +/- 0.04 min(-1) in the men. The turnover rate of arachidonic acid was similar in both sexes; calculated per kg body weight it was significantly higher in the women. No sex differences were observed in the concentration or turnover of plasma free oleic acid when corrected for differences in body size. The composition of the free fatty acid fraction differed between the sexes, the female subjects having a lower proportion of saturated fatty acids and higher proportions of oleic and eicosenoic acids. The results indicate that the metabolism of polyunsaturated fatty acids in man is influenced by gonadal steroid hormones.

Adult↗
PubMed1975

Prostaglandin release and mechanical perfromance in the isolated rabbit heart during induced changes in the internal environment.

The isolated rabbit heart was perfused according to the Langendorff technique. Prostaglandins in the effluent from the organ were identified by use of thin layer chromatography and assayed on the rat stomach strip. The effect of alterations of the physical and chemical conditions of the perfusion medium on the overflow of prostaglandins from the heart was studied. In addition, the capacity of noradrenaline and acetylcholine to release prostaglandins was tested. Acidosis, hyperthermia, hypothermia, hypotension, hyperosmoaarity and increased [K+] OR [Ca++] levels, while all inducing marked changes in the mechanical activity of the heart, did not induceporstaglandin release. Hypoxia, on the other hand, stimulated the liberation of prostaglandins. Noradrenaline was a potent agent for stimulation of prostaglandin release, in the absence of alpha- and betaadrenergic receptor blockade. Acetylcholine was also found to liberate prostaglandins, by activation of muscarinic receptors. The prostaglandin releasing capacity of acetylcholine was about 3 times weaker than that of noradrenaline. It is concluded that the release of prostaglandins from the rabbit heart is not dependent on the mechanical activity of the organ. Furthermore, it is suggested that prostaglandins released by hypoxia may play an important roli in the development of reactive hyperemia. Finally it is stated that the release of prostaglandins from the heart caused by acetylcholine may constitute the negative link in an endogenous prostaglandin mediated feed-back inhibition of the release of acetycholine from parasympathetic nerve endings.

Acetylcholine↗
PubMed1975

Hypoxia-induced prostaglandin release from rabbit heart.

Rabbit hearts were perfused at a pressure of 60 cm H2O with 37 degrees C Tyrode solution aerated with 5% CO2 in O2. The effluent from the heart was collected in four consecutive 10-min periods. The samples were analyzed for prostaglandins of the E series (PGE), using thin layer chromatography for identification and assay on the superfused rat stomach strip for quantitative estimation. Three different series of experiments were performed, the hearts in each series during the second effluent collection period being perfused under conditions of either hypoxia (Tyrode solution aerated with 5% O2 and 5% CO2 in N2), absence of glucose in the Tyrode solution, or hypotension/low perfusion flow (perfusion pressure lowered to 30cm H2O). In the series where glucose was omitted or hypotension/low perfusion flow was induced during the second effluent collection period, the outflow of PGE decreased exponentially throughout the four periods. In the series where hypoxia was maintained during the second effluent collection period, a marked increase in the outflow of PGE was noted after the end of hypoxia. Prostaglandins of the E series are powerful vasodilators, and the PG released may, by inducing coronary vasodilation, counteract the hypoxia. However, it has been shown that, in human plasma, conversion of arachidonic acid to PGE is parallelled by platelet aggregation. Therefore, if PG synthesis is also stimulated by hypoxia in man, myocardial ischemia must be considered as a possible mechanism for platelet aggregation and subsequent coronary thrombosis.

Animals↗
PubMed1974

Release of prostaglandin from the rabbit isolated heart following vagal nerve stimulation or acetylcholine infusion.

1 Rabbit hearts were perfused by the Langendorff technique. The lipid fraction in the perfusate from the heart was isolated and analysed for prostaglandins by thin layer chromatography and quantitative assay on the rat isolated stomach strip.2 Infusion of acetylcholine at a rate of 8 mug/min significantly increased the outflow of prostaglandins from the heart, from 1.8 to 6.2 ng/minute.3 Addition of atropine (1 mug/ml) to the perfusing medium completely abolished not only the mechanical response but also the increase in outflow of prostaglandins caused by infusion of acetylcholine.4 Bilateral stimulation of the parasympathetic nerves to the heart at 5 Hz also significantly increased the outflow of prostaglandins from the organ from 5.2 to 8.3 ng/minute.5 Both prostaglandin E(1) and E(2) were isolated from the lipid fraction of the perfusate.6 The role of prostaglandins in relation to autonomic neurotransmission in the heart is discussed.

Acetylcholine↗