Effect of Some Drugs on Human Umbilical Artery in Vitro

Abstract

Investigation of the actions of drugs on vascular smooth muscle is frequently complicated by indirect actions mediated through neural elements. However, valuable information on the direct actions of drugs on vascular smooth muscle can often be obtained from experiments on nerve-free preparations. Perfused placental vessels (von Euler, 1938;Panigel, 1962), spirally cut umbilical arterial and venous strips (Somlyo, Woo & Somlyo, 1965), chick amniotic membrane (Ferguson, 1940;Cuthbert, 1963), and rabbit ear vessels before innervation (Clark & Clark, 1943) have been employed in the past for this purpose. A nerve-free vascular smooth muscle preparation, responding uniformly to various autonomic transmitters could also be used to elucidate the nature of their storage and release.In the present study the isolated perfused human umbilical artery was used to study the direct action of drugs on the vascular smooth muscle. It was observed that with the method employed many vasoactive agents gave fairly uniform responses. Modification of these responses by other drugs could, therefore, be studied. The preparation exhibited spontaneous tone and could give a dilator response to drugs, without the previous addition of a spasmogenic agent. METHODSUmbilical cords were obtained from the Maternity Ward of Shree Sayaji General Hospital, Baroda, as soon after delivery as possible. After identifying the foetal and the placental ends, every cord was firmly tied at both ends and kept in a flask containing perfusion fluid of the following composition (g/l.): sodium chloride, 9.00; potassium chloride, 0.42; calcium chloride, 0.24, sodium bicarbonate, 0.2 and dextrose, 1.0. Tying ensured that any blood in the lumen of the vessels remained in a fluid state and could subsequently be washed out easily. In earlier experiments when the cords were not tied, many of them could not be used because of the intravascular clotting. The cords remained viable for about 5 hr after delivery. Experiments were, therefore, started soon after the collection of the cords.Before cannulation the cords were placed in fresh perfusion fluid at 34' C for 10 min. This considerably reduced the spasm of the vessels and thus facilitated cannulation. A piece of cord about 5 in. long was selected (excluding any portion with injury and pseudoknots), and this was cut at both ends with a sharp pair of scissors. One of the umbilical arteries was cannulated at the

Release of endothelium-derived relaxing factor from human umbilical vessels.

“…2O~22 Only one study mentions a transient dilation followed by a constriction after the addition of histamine to perfused umbilical arteries. 23 In our tests, no relaxation effect could be obtained with histamine on umbilical preparations mounted for isometric tension recording in the presence or absence of indomethacin and contracted with serotonin. However, Clymann et al 24 reported marked increases in cGMP levels in the human umbilical arteries in response to low concentrations of histamine, an effect that is also mediated by an H,-receptor mechanism, while they obtained only moderate increases in cGMP in response to serotonin and acetylcholine at high concentrations.…”

Relaxations of the isolated portal vein of the rabbit induced by nicotine and electrical stimulation

“…Part of these relaxations was due to activation of sympathetic nerves followed by excitation of a-adrenoceptors, for they were shortened by antagonists of a-adrenoceptors, adrenergic neurone blocking agents or by tetrodotoxin. Vasodilatation resulting from excitation of a-adrenoceptors by noradrenaline has been described (Gokhale, Gulati, Kelkar & Kelkar, 1966), but we were only able to induce pure relaxations with noradrenaline after a-adrenoceptor block. Relaxations following contractions induced by noradrenaline were occasionally seen, but the loss of tone was prolonged and recovery to the initial resting tone often took 30 min.…”

Mechanisms of action of noradrenaline and carbachol on smooth muscle of guinea‐pig anterior mesenteric artery.

“…the release of noradrenaline and the amplitude of the excitatory junctional potential are both reduced by low concentrations of acetylcholine (Steinsland, Furchgott & Kirpekar, 1973;Vanhoutte, Lorenz & Tyce, 1973;Vanhoutte, 1976;Kuriyama & Suzuki, 1981). However, in addition to their presence on sympathetic nerve endings, both excitatory and inhibitory muscarinic receptors occur elsewhere in blood vessels: contraction to acetylcholine has often been reported for the smooth muscle of larger blood vessels (Furchgott, 1955) and these include non-innervated umbilical arteries (Gokhale, Gulati, Kelkar & Kelkar, 1966) which implies a direct action. Relaxation has been described in a number of arteries (Kuriyama & Suzuki, 1978;Furchgott & Zawadzki, 1980;Takata, 1980).…”