The Fall of Blood Pressure Caused by Intravenous Morphine in the Rat and the Cat

Abstract

In 1933 Schmidt and Livingstone attempted to determine the cause of the marked fall of blood pressure which results when morphine sulphate is injected intravenously into the cat or the dog. They showed that. the phenomenon exhibited tachyphylaxis and that it was unaffected by ether, urethane, barbitone, or phenobarbitone. They were unable to arrive at any definite conclusions and could only suggest that " depression of the vasomotor centre plays some part in this effect, but most of it is due to dilatation of cutaneous and muscular blood vessels by direct action upon their walls." Sollmann and Pilcher (1917) reported that morphine evoked the triple response in the human skin, an observation which was confirmed by Lewis (1927). Since that time Nasmyth and Stewart (1950) have shown that the weals caused by morphine in human skin are reduced by antihistamine drugs. Feldberg and Paton (1950) reported that the intra-arterial injection of morphine into the isolated perfused gastrocnemius muscle of the cat caused the appearance of histamine in the effluent, and later (Feldberg and Paton, 1951) showed that the drug also released histamine from the cat's skin and that after its intravenous injection into the intact animal the plasma histamine was raised. They considered that the fall of blood pressure caused by the intravenous injection of morphine could not be wholly accounted for by the release of histamine.In this work we have shown that the effect is complex and that at least three factors which would affect the blood pressure are involved when morphine is injected intravenously. METHODSAnaesthesia.-All the rats from which records of blood pressure were taken were anaesthetized with urethane (7 ml./kg. of a 25 per cent (w/v) solution injected subcutaneously). Rats which received injections of morphine sulphate into the jugular vein 24 hours before records of blood pressure were taken from them were anaesthetized with ether while the vein was exposed.Cats were anaesthetized with ether followed by 80 mg./kg. of chloralose intravenously.Records of blood pressure.-All animals except decerebrate and spinal cats, from which records of blood pressure were taken, were heparinized. The apparatus described by Condon (1951) was used to record the blood pressure of the rats.

The Action of Morphine and Related Substances on Contraction and on Acetylcholine Output of Coaxially Stimulated Guinea‐pig Ileum

“…Two other processes might contribute to an increased activity of the intestine-after morphine, although they can hardly account for all of the results reported. In the first place, morphine is a histamine-liberator (Feldberg and Paton, 1951;Evans, Nasmyth and Stewart, 1952), and it is known that histamine-liberators can increase the motility of the intestine, although only with large doses can a frank contraction be produced (Feldberg and Smith, 1954). Secondly, in the experiments reported above, it was noticed that sometimes, following a sustained exposure to morphine, and after the morphine was washed out, the resting acetylcholine output increased ; whether this represented an increased leakiness of the cholinergic nerve endings, or a change in the output of acetylcholine from non-nervous sources, it may contribute to the enhanced though rather incoordinate motility of the gut produced sometimes by morphine administration.…”

Cardiovascular effects of morphine, pethidine, diamorphine and nalorphine on the cat and rabbit

“…The same conclusion might be drawn from the observation that, on one occasion, nalorphine reversed the depressor effect of pethidine. Evans et al (1952) obtained direct evidence of catecholamine release from the adrenal medulla by morphine in the cat and, as the initial rise of blood pressure can be very marked in spinal cats (Kalyaalp & Kaymakqalan, 1966), any reflex or central contribution to the mechanism is not essential.…”

“…During the latter period, which may be protracted after large doses of morphine, the preparation shows tachyphylaxis to the depressor effect of this drug, and this state of hyposensitivity is still present even if the blood pressure is artificially raised to its original level (Schmidt & Livingston, 1933). Moreover, even after the pressure has recovered naturally, the depressor response to a given dose of morphine is considerably less, for a long time, in all species studied (for example, 5-24 h in the rat: Evans et al, 1952).…”

“…The depressor response to 2-5 mg/kg of these substances typically consists of an initial, rapid fall, chiefly due to histamine release in the cat (Feldberg & Paton, 1951 ;Evans et al, 1952;Kayaalp & Kaymakcalan, 1966) and the dog (Van Arman & Sturtevant, 1958), followed by a longer period of hypotension during which the blood pressure slowly recovers. During the latter period, which may be protracted after large doses of morphine, the preparation shows tachyphylaxis to the depressor effect of this drug, and this state of hyposensitivity is still present even if the blood pressure is artificially raised to its original level (Schmidt & Livingston, 1933).…”

“…When morphine or pethidine is administered intravenously to anaesthetized laboratory animals, the predominant effect is hypotension although this may be preceded or interrupted by an evanescent pressor effect due to the release of catecholamines from the adrenal medulla in some species (for example, cat, 4 mg/kg morphine: Evans, Nasmyth & Stewart, 1952). The depressor response to 2-5 mg/kg of these substances typically consists of an initial, rapid fall, chiefly due to histamine release in the cat (Feldberg & Paton, 1951 ;Evans et al, 1952;Kayaalp & Kaymakcalan, 1966) and the dog (Van Arman & Sturtevant, 1958), followed by a longer period of hypotension during which the blood pressure slowly recovers.…”