No abstract

Chronic cadmium chloride (CdCl₂ 0.5 and 1.0 mg/kg, i.p.) treatment in female albino rats for 2 weeks resulted in elevation of blood pressure. In chronic CdCl₂-treated rats the pressor responses to different doses of noradrenaline, angiotensin II and depressor responses to acetylcholine and isoprenaline were unaltered. In rat hindquarter preparation there was elevation of perfusion pressure and the sensitivity of vascular bed to noradrenaline was increased in the CdCl₂-induced hypertensive rats. Complete bilateral adrenalectomy or chemical sympathectomy or treatment with captopril did not prevent the development of CdCl₂-induced hypertension. Treatment with verapamil (15 mg/kg/day, p.o.) or nifedipine (10 mg/kg/day, p.o.) for 2 weeks prevented the development of hypertension with chronic CdCl₂ treatment. It is suggested that chronic treatment of rats with CdCl₂ induces hypertension. It is possible that cadmium mimics the calcium ion for the induction of hypertension in rats.

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

Antagonism by chlorpromazine of the responses of the rabbit aortic strip and the rat seminal vesicle to adrenaline and noradrenaline fulfils the conditions of competitive antagonism. Chlorpromazine was a remarkably potent antagonist (pA2 approximately 14) of adrenaline and noradrenaline. In the cat anaesthetized with chloralose small doses (1.8 to 4.5 mg/kg) of chlorpromazine greatly reduced or reversed the pressor effect of adrenaline but the pressor effect of noradrenaline was unaffected. A larger dose (9 mg/kg) of chlorpromazine slightly reduced the pressor effect of noradrenaline but caused a spectacular reversal of the pressor effect of adrenaline. This difference was not observed in rabbits and in cats treated with dichloroisoprenaline. Chlorpromazine potentiated the depressor effect of isoprenaline. On the basis of these findings it is concluded that in the cat chlorpromazine in small doses (1.8 to 4.5 mg/kg) has no real adrenergic blocking action and that the selective block of adrenaline pressor effects by these doses is due to a potentiation of adrenergic vasodilatation. Large doses (7.2 to 28.8 mg/kg) of chlorpromazine reduced the pressor effect of noradrenaline; reciprocal analysis showed that this inhibition is competitive.