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Strips of Taenia coli from guinea pigs were incubated under physiological conditions in an organ bath. Contractile activity was monitored with an isometric force transducer and resting tension was adjusted with a micrometer drive. Strips in different functional states were fixed for subsequent examination in the electron microscope by the addition of glutaraldehyde to the organ bath. The density-distribution of thick myofilament profiles was obtained for relaxed and contracted strips. Thich myofilaments appear to be present in equal numbers in cells of spontaneously active, relaxed, and contracted strips.

The disappearance of phe(3)-oxytocin, val(3)-oxytocin and oxytocin from the circulation of male rats was shown to be due to qualitatively similar mechanisms, that is, it depends on uptake in the kidneys and organs of the splanchnic vascular area. However, compared to phe(3)-oxytocin and oxytocin (whose half-lives were essentially similar) val(3)-oxytocin took twice as long to reach half its initial blood concentration. In lactating rats the mammary glands probably participated in the uptake of phe(3)-oxytocin, but the rate of disappearance of val(3)-oxytocin was not different from that in non-lactating animals. In male nephrectomized rats without splanchnic circulation, phe(3)-oxytocin, unlike val(3)-oxytocin, was quickly distributed in a volume equal to two-thirds of the total body water. Using oxytocin as the standard, val(3)-oxytocin and phe(3)-oxytocin were more potent when assayed on a superfused uterus or on a rat uterus in vivo than when assayed by the pharmacopoeial method (1958) on the isolated uterus in an organ bath. The difficulties of assaying oxytocin analogues against oxytocin (or the international standard preparation) are discussed.

Two simple arrangements are described by means of which the Pco2 and Po2 of physiological salt solutions placed in open vessels can easily be adjusted and maintained at known and constant levels during biological experiments on immersed living tissue. The characteristic feature of the proposed arrangements is that a certain fraction of the area of the free surface of the fluid, under standardized stirring conditions, is exposed to an atmosphere with known and constant concentrations of CO2 and O2. The constancy of the Pco2 and the Po2 in the fluid is practically uninfluenced by the additional stirring caused by the biological experiments for which the bath is used.

DURING work on drug antagonism, it was found incidentally that isolated small intestines of guinea pigs contracted reversibly with picric acid, and the mode of this action was examined in detail, using the organ bath of 30 ml. at the bath temperature of 26° C., on isolated small intestines of guinea pigs1. All the results given here are the mean of at least ten experiments.

The effect of the 8 newly recognized prostaglandins on isolated human myometrium and rabbit jejunum is described. The myometrial strips were obtained from patients undergoing hysterectomy due to myomatous changes in the uterus. Immediately after surgical removal of the uterus suitable pieces of apparently normal myometrium were taken from the corpus part of the myometrium. 4 strips were cut out and each was mounted in a separate 40 millimeter curvette in an organ bath. For determination of the effect on isolated rabbit jejunum about 15 centimeters of the duodenum-jejunum was removed. The compounds tested were PGE1 PGA1 PGA2 PGB1 PGB2 19-hydroxy-PGA1 19-hydroxy-PGA2 19-hydroxy-PGB1 and 19-hydroxy-PGB2. In the experiments where human myometrium was used the compounds were administered to the baths in increasing doses beginning with an ineffective dose until significant effect was obtained. The effects of the prostaglandins were recorded on 52 myometrial strips from 13 uteri. All 8 compounds inhibited the spontaneous motility of the non-pregnant isolated myometrium and the effect was similar to that of PGE1. In 2 cases of 5 high doses of 19-hydroxy-PGB1 instead stimulated the motility. Isolated rabbit intestine was stimulated in a similar way as PGE1 by the 8 tested compounds.

AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips. METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile responses to electrical field stimulation were recorded on a physiograph in an isotonic manner after administration of cumulative concentrations of indomethacin. The effects of indomethacin on the strips pretreated with KATP channel modulators, diazoxide and glybenclamide were studied. RESULTS: Treatment of the transverse strips with indomethacin resulted in a concentration-dependent inhibitory response. In longitudinal strips, biphasic responses were seen, which included a stimulatory response at low concentrations of indomethacin, followed by an inhibitory response at higher concentrations. Diazoxide pre-treatment inhibited the stimulatory response of longitudinal strips. Glybenclamide pre-treatment not only blocked inhibitory effect of the low concentrations of indomethacin on transverse strips, but also increased the amplitude of contractions. Moreover, the drug decreased the amplitude of contractions in longitudinal strips. CONCLUSION: Responses of the isolated longitudinal and transverse rat gastric fundus strips to indomethacin are not similar, and are influenced by KATP channel modulators.

OBJECTIVE To study if the present widely used artemisin derived anti-malaria drugs have vascular effects. METHODS Aortic rings were obtained from adult male Sprague-Dawley rats. The rings were mounted in an organ bath and tension recorded using isometric force transducers. After pre-contraction with noradrenaline, cumulative doses of artesunate were added to the bath containing the rings. The effects of nitric oxide inhibition with L-NAME, on the responses to artesunate were also assessed. Lastly the effects on the contractile responses of the rings to noradrenaline (NA) were determined before and after incubation in artesunate. RESULTS Cumulative addition of artesunate from 6 x 10(-4) to 6 x 10(-1) mg/ml resulted in relaxation of pre-contracted aortic rings. L-NAME significantly reduced the relaxation response to artesunate (P < 0.05). Vascular contraction response to NA was significantly reduced (P < 0.01) following the addition of artesunate. CONCLUSION Artesunate causes relaxation of precontracted rat aortic rings which is partly mediated by Nitric Oxide (EDRF). It also reduces the contractile responses of the rings to noradrenaline.

A superfusion bioassay for platelet-activating factor is described using various types of tissues. By washing the tissue with 0.1–0.5% bovine serum albumin for 2–3 min after each addition of platelet-activating factor, desensitization did not develop in most tissues studied. Because of the ability to apply a sample directly onto an assay tissue with negligible dilution, this bioassay can detect smaller amounts of platelet-activating factor than those previously reported in which an organ bath was utilized. The ascending colon of the rat and dog appeared to be the most sensitive of the tissues tested, with a limit of detectability in the range of 100–500 fg. Repeated additions of platelet-activating factor could be made for up to 4 h without desensitization. Release of platelet-activating factor from samples of rat stomach was measured using the superfusion bioassay and a platelet aggregation bioassay. There was a significant correlation (r = 0.96; p

In a previous paper an esterase presenting kinin-like forming activity and oxytocic action was described in rat urine. The oxytocic action appears to be independent of the presence of a substrate in the uterus (Beraldo, Araujo and Mares Guia, 1966).

Methylthioadenosine(MTA) is a naturally occurring purine nucleoside which has been shown to have numerous effects on cell metabolism and function. We studied the action of MTA on tracheal smooth muscle, using isolated guinea pig tracheal rings. The tracheal rings were suspended in a 10 ml organ bath, containing atropinized Krebs-Henseleit solution. When MTA was added to the medium, relaxation of isolated guinea pig tracheal rings occurred after a latent period and was dose-dependent over concentrations ranging from 50 to 1000 μM. Pretreatment of the tracheal rings with 100 μM MTA inhibited the contraction produced by varying concentrations of histamine or leukotriene D4. The inhibition caused by 100 μM MTA was dependent on histamine or leukotriene D4 concentrations, ie 51% at 0.25 μg/ml histamine, 42.5% at 1.0 μg/ml histamine, 22% at 2.0 μg/ml histamine, and 81% at 0.5 μg LTD4, 50% at 1 μg LTD and 46.2% at 2 μg LTD4. The tracheal contractions induced by a standard concentration of histamine(1 μg/ml or leukotriene D4 (1 μg) were inhibited dose-dependently by pretreatment with MTA, ie 22% (histamine), 8.4%(leukotriene D4 at 10 μM, and 58%(histamine), 25%(leukotriene D4) at 100 μM. 500 μM of MTA blocked completely the contraction induced by histamine or leukotriene D4. It seems that MTA is an important modulator of tracheal smooth muscle cell function.

The effects of ketamine on the peripheral sympathetic nervous system were studied in vitro by observing the amplitude of the nerve-mediated contraction of the vasa deferentia isolated from guinea pigs. Ketamine dissolved in the perfusate of an organ bath was applied to the tissues for 30 minutes and then washed out with a perfusate lacking ketamine for 90 minutes. Ketamine in concentrations of 10(-8) and 10(-7) g/ml had no effect on contraction induced by hypogastric nerve (preganglionic) stimulation. At 10(-6) g/ml, the drug had no significant effect during application but was associated with increased contractions during washout. At 10(-5) and 10(-4) g/ml, the drug showed a dose-related depression during application and an increase in contractions during washout after a 10(-5) g/ml. Ketamine, 10(-5) g/ml, increased contraction following transmural (postganglionic) stimulation and had a depressant effect at a concentration of 10(-4) g/ml. It is concluded (1) that ketamine has dual effects on the nerve-mediated contraction of the vasa defentia and (2) that cardiovascular responses to ketamine include peripheral effects of ketamine on sympathetic ganglia.