The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

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.

Although the responses of isolated venous strips to several vasoactive substances and the modification of these responses by antagonists have been studied (Sutter, 1965), data on the quantitative aspects of such antagonism are not available. We have examined the effects of some vasoactive substances on the post caval venous strips of rabbits and made a quantitative study of the antagonistic effect of blocking drugs. Some experiments using the " receptor protection " technique of Furchgott (1954) were also performed. It was expected that the data on the quantitative aspects of antagonism and those obtained with the " receptor protection " experiments would yield information about the receptors in the veins. METHODSStrips were obtained from the posterior vena cava of young rabbits of either sex, killed by a blow on the head and prepared in the manner described by Sutter (1965). Spirally cut strips 3-3.5 cm long and 2-3 mm wide were suspended in a 40-ml. organ bath containing Krebs bicarbonate solution of the following composition (g/l. of distilled water): NaCl, 6.88; KCI, 0.42; anhydrous CaC12, 0.28; anhydrous MgCl2, 0.112; NaH2PO4, 0.18; NaHCO3, 2.1; and dextrose, 1.8. The solution was maintained at 370-380 C and 5% carbon dioxide in oxygen was bubbled through it in both the bath and the reservoir. The pH of the solution was then 7.4. The strips were suspended in the bath for at least 30 min before study. Isotonic contractions at 0.5 g tension were recorded on a smoked drum at ten times amplification. Dose-response curves for noradrenaline (6.5x 10-8, 1.3x 10-7, 2.6x l0-7, 5.2 x 1o-7 and 1.04x 10-6) and for histamine (1.25 x 10-7, 2.5 Xl0-7, Sxl0-7, 1 X 10-6 and 2 x 10-6) were obtained by the cumulative administration of increasing concentrations of the amines, allowing the contraction to develop fully after each administration (2 min for noradrenaline and 2.5 min for histamine). In individual experiments the height of maximal contraction was first determined by the cumulative addition of the amines and the preparation was then repeatedly washed for 60 min. Cumulative dose/response curves for noradrenaline and histamine with responses between 20 and 80% of the maximal were then determined at intervals of 45 min on each strip before the administration of the antagonist (phentolamine or antazoline). In studies on antagonism, the antagonist was kept in the bath for 20 min before the addition of the agonist and remained in the bath thereafter.An attempt was also made to obtain contractile responses of the venous strip to several other known in vitro vasoactive substances, such as 5-hydroxytryptamine, acetylcholine, angiotensin and bradykinin. If a given agent elicited a contraction, several known antagonistic drugs were used to obliterate the response.