Reflex and Direct Cardiopulmonary Effects of 5-OH-Tryptamine (Serotonin)

Various reports suggest that 5-hydroxytryptamine (5HT) can cause bronchoconstriction. Thus, Reid and Rand (1952) (Gaddum, Hebb, Silver, and Swan, 1953) and guinea-pig (Bhattacharya, 1955). A constrictor effect of 5HT has also been noted in the tracheal chain of the guineapig (Freyburger et al., 1952) and cat (Sinha and West, 1953). Furthermore, 5HT administered as an aerosol causes dyspnoea in the guinea-pig, resembling that produced by histamine or acetylcholine (Herxheimer, 1953a(Herxheimer, , 1953b(Herxheimer, , and 1955.As yet, the effect of 5HT on tidal air has not been investigated in the intact and spinal animal. It therefore seemed of interest to make such an investigation with a view to obtaining further information on the mode of action. Another purpose of the study was to investigate whether agents found to be potent antagonists of 5HT in isolated organs in vitro also antagonize the bronchoconstriction induced by SHT in vivo. METHODSCats were anaesthetized with a mixture of chloralose (0.05 g./kg.) and urethane (0.5 g./kg.) administered subcutaneously. In the course of some experiments first the vagi were cut and later the spinal cord was sectioned at C 1. Guinea-pigs were anaesthetized by intraperitoneal administration of urethane (1.2 g. /kg.). Spinal cats and guinea-pigs were also used, the operation being conducted under ether anaesthesia.

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confidence: 99%

The Effects of 5‐hydroxytryptamine and Its Antagonists on Tidal Air

Konzett¹

1956

“…An antagonism of this kind would be of great interest in clinical cases of embolism or thrombosis. A local release of 5-HT could, by way of vasoconstriction, contribute to the impairment of the local circulation in such patients (Comroe, van Lingen, Stroud, and Roncoroni, 1953).…”

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confidence: 99%

The Action of 5‐hydroxytryptamine and Some of Its Antagonists on the Umbilical Vessels of the Human Placenta

Åström

Samelius

1957

The vasoconstrictor action of 5-hydroxytryptamine (5-HT) in the human placental preparation is about 10 times stronger than that of adrenaline and is antagonized by anti-adrenaline compounds like phentolamine. Both 5-HT and adrenaline are antagonized by yohimbine and chlorpromazine. Specific and strong anti-5-HT action is demonstrated for lysergic acid diethylamide (LSD) and tryptamine. Both LSD and tryptamine in larger doses have a vasoconstrictor action. Mescaline has no certain modifying effect on the action of 5-HT, but itself causes vasoconstriction in large doses. The antihistamine drug phenbenzamine in histamine blocking doses abolishes the action of 5-HT in half the preparations tested. The ganglionic blocking agent trimetaphan in large doses antagonizes the action of 5-HT added subsequently, and also, to a lesser degree, the effect of adrenaline. Hexamethonium and tetraethylammonium bromides are ineffective in this preparation. No certain modifying action of reserpine on subsequently added 5-HT could be demonstrated, and the same was true for heparin even in very high concentrations.5-Hydroxytryptamine (5-HT) continues to attract considerable attention as a possible factor in different experimentally produced psychotic conditions in animals and as a compound possessing vascular effects. Although 5-HT has rather weak and inconsistent effects upon the systemic blood pressure in different animals and in man (Erspamer, 1954), evidence is accumulating for its strong vasoconstrictor action in certain local vascular beds.In a previous report from this laboratory (Eliasson and Astrom, 1955), the pharmacological actions of a series of compounds were studied on the blood vessels of isolated human placentas. 5-HT was included in this series, and its actions were compared with those of adrenaline and noradrenaline. It was shown that 5-HT, in the same manner as the catechol derivatives, caused a constriction of the umbilical vessels and its potency in this respect was about 10 times that of adrenaline. 5-HT showed many pharmacological similarities to adrenaline and noradrenaline; thus its action in this preparation was abolished by dihydroergotamine and enhanced by cocaine. The same ratio between the potency of 5-HT and adrenaline has been demonstrated in the lung vessels of the dog and the cat by Ginzel and Kottegoda (1953).In the experiments here the action of 5-HT on the placenta has been studied further and special consideration has been given to a series of drugs known to antagonize the actions of 5-HT in other preparations. Since the umbilical vessels do not receive any nerve supply (Schmitt, 1922;Guarna, 1934) it was felt that a study of 5-HT antagonists in this preparation might yield information of interest concerning the pharmacological mechanisms involved. METHODSHuman placentae were obtained from the hospital as soon as possible after delivery.

“…Comroe, Van Lingen, Stroud, and Roncoroni (1953) observed that rapid intravenous injection of HT into cats caused one or all of the following effects: bradycardia, hypotension, apnoea, bronchial constriction, and an increase of right ventricular pressure. They showed that almost all these effects were, or might be, reflex; they concluded that the afferent nerve fibres were mainly in the vagi, and that the sensory receptors for the apnoea, bradycardia, and hypotension lie in the areas supplied by the pulmonary vessels and branches of the ascending aorta.…”

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confidence: 99%

“…This increase of flow was sometimes followed by a reduction. Comroe et al (1953) believed that the hypotension caused by HT was mainly due to the bradycardia. In our experiments, after the animal was atropinized (1.5 mg./kg.)…”

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confidence: 99%

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Cardiovascular and Respiratory Actions of 5‐hydroxytryptamine in the Cat

Kottegoda

Mott

1955

The respiratory and cardiovascular effects of 5-hydroxytryptamine (HT) in the cat have been described by several authors, but it is still not clear to what extent its effects are due to reflex or to direct actions.HT causes a temporary arrest of breathing in the cat (Reid and Rand, 1951). Ginzel and Kottegoda (1954) observed that, when small doses (2-6 ,ug.) were injected into the carotid sinus region of the cat, there was a brief apnoea followed by stimulation of breathing; these changes were accompanied by -a fall of blood pressure. Since denervation of the carotid sinus region abolished these effects they concluded that HT acts on either baro-or chemo-receptors. They also found 1954) reported that HT stimulates pulmonary stretch receptors, but admitted that some other type of sensory vagal nerve fibres might also be excited. Mott and Paintal (1953), in a small series of experiments, showed that the reflex apnoea caused by HT in the cat arose from sensory receptors lying between the great veins and the left atrium, and that it was abolished by cutting the vagi but not by cooling them to 2-3°C. Mott and Paintal (1953) and Paintal (1954) were unable to find any evidence that this substance stimulates or sensitizes pulmonary stretch, right or left atrial, or depressor, nerve endings. They concluded that the reflex apnoea caused by HT in the cat resembled that for the amidine compounds, and differed from that caused by veratridine; the latter has been shown to stimulate pulmonary stretch fibres (Meier, Bein, and Helmich, 1949;Dawes, Mott, and Widdicombe, 1951;Paintal, 1953). Hence there exists a difference of opinion regarding the site and mode of action of HT in causing reflex apnoea. The present investigation was undertaken in the hope of elucidating this question, and also with a view to analysing further reflex actions of HT in the cat. METHODSThe respiratory and cardiovascular changes produced by intravenous injections of HT were studied in 13 cats (1.5-3.2 kg.). The animals were anaesthetized with chloralose (60 mg./kg.) and the respiratory movements recorded by the body plethysmograph (Dawes, Mott, and Widdicombe, 1951). Carotid blood pressure was recorded by a mercury manometer and injections were made into the jugular vein. The cervical vagi were cooled by the method described by Dawes et al. (1951). Both vagi were cooled simultaneously to the same temperature.The effect of intravenous injections of HT on the blood flow in the hind legs was investigated in four cats (2.3-3.4 kg.). These animals were anaesthetized with pentobarbitone (30 mg./kg. intraperitoneally) and heparinized. The aorta was divided in the lower abdomen, a pump unit was introduced between the