Prostaglandins are released when the sympathetic nerves supplying the rat epididymal fat pad in vitro are stimulated (Shaw, 1966). It is not yet known whether this is a general phenomenon associated with adrenergic nerve stimulation but the experiments described in this paper show that prostaglandin E2 is released when the splenic nerve is stimulated. A preliminary account of this work has already been published (Davies, Horton & Withrington, 1967).In the investigation reported here we collected venous blood samples from the perfused dog's spleen in order to detect any prostaglandin release when the splenic nerve was stimulated. A large increase in prostaglandin E2 output was found. METHODSBlood-perfused dog spleen. An isolated spleen was perfused with blood from the femoral artery of a second (donor) dog using the technique described in the following paper (Davies & Withrington, 1968). The splenic venous blood was returned to the femoral vein of the donor except during the collection of a sample, when it was diverted out of a side arm. During the collection of a sample, blood from a reservoir was pumped into the donor. Electrodes were placed on the splenic nerve and the spleen was bathed in liquid paraffin at 370 C. The nerve was stimulated with 50 V pulses of 0.5 msec duration at 10/sec. Extraction procedures. The procedures are outlined in Fig. 1

Summary The responses of the smooth muscle of the capsule and blood vessels of the isolated, perfused human spleen to sympathetic nerve stimulation, adrenaline, noradrenaline, angiotensin, oxytocin, vasopressin, isoprenaline and acetylcholine have been investigated and compared with those of dog spleen. Stimulation of the postganglionic sympathetic nerves to the human spleen at frequencies of 3–10 Hz evoked graded vasoconstriction but very small changes in spleen volume. The injection of adrenaline and noradrenaline in doses of 0·25–25 μg to the human spleen produced graded increases in splenic vascular resistance with very small decreases in spleen volume. Administration of the α‐adrenoceptor blocking drug phenoxybenzamine completely abolished or considerably reduced the vascular responses of the human spleen to sympathetic nerve stimulation or the injection of noradrenaline. The vascular action of adrenaline was often reversed to elicit a vasodilatation after phenoxybenzamine suggesting the presence of β‐adrenoceptors in the vascular bed. This was confirmed by the administration of isoprenaline which induced a marked reduction in vascular resistance of the human spleen. The polypeptides angiotensin and vasopressin induced a marked vasoconstriction in the human spleen without changes in the spleen volume. These effects were uninfluenced by the administration of phenoxybenzamine. The polypeptide oxytocin caused a slight vasodilatation in the human spleen, an effect almost exactly mimicked by the preservative chlorobutanol. Preliminary experiments suggest that noradrenaline is the transmitter released by the postganglionic nerves to the human spleen. These results provide direct evidence that the normal human spleen, unlike that of the dog, does not have a reservoir function. It is suggested that contractions of the enlarged human spleen may occur in various pathological conditions.

Brown & Gillespie (1957) studied the output of sympathetic transmitter in the venous blood from the spleen of the cat resulting from stimulation of the splenic nerves. They showed that the output depended upon the frequency of stimulation, being maximal at 30/sec, and falling away at higher and lower frequencies. No noradrenaline could be detected in the venous blood at frequencies lower than 10/sec. The administration of the adrenergic blocking agents dibenamine and dibenyline increased the output at all frequencies below 30/sec. The explanation suggested for these results was that combination with tissue receptors precedes the metabolic removal of liberated noradrenaline; at frequencies below 10/sec the unpoisoned receptor mechanism can remove all the liberated noradrenaline, and so none can be detected in the venous effluent. At frequencies between 10 and 30/sec increasing amounts overflow into the circulation because the receptor mechanism is swamped. The administration of a blocking agent prevents the uptake of transmitter by the tissue, and the noradrenaline then appearing in the venous blood gives a measure of the amount liberated by the nerve endings. It is therefore possible by measuring the amount of transmitter in the venous blood, before and after a blocking agent is given, to determine, for any frequency of stimulation, the amount of transmitter liberated, the amount taken up by the tissue, and the amount normally overflowing.Some experiments made for another purpose suggested that' previous activity might modify the amount of the transmitter overflowing when the nerves were stimulated. It had been found, for instance, that a first group of stimuli at 30/sec given to the nerve after a rest of 1-11 hr yielded 450 pg/stimulus, whereas a second, given 10 min later, produced an overflow of 1025 pg/stimulus (mean of 5 observations). These experiments led us to think that interruption of the normal constant centrifugal discharge of the sympathetic neurones might alter the peripheral processes of liberation

Groups of young, adult males and females performed the handgrip and standing long jump tests. Their total forearm and leg volumes were calculated from a series of circumference and length measurements, and the lean volumes (bone + muscle) calculated by taking the skinfold thickness into consideration. In the handgrip, the mean female performance was 298 N compared with 496 N for the males. In the standing long jump, mean performance expressed as distance x body mass was 87.3 kg.m for females compared with 137.7 kg.m for males. These superior performances of males could simply reflect their greater muscle mass, as the mean lean volumes of female and male limbs respectively were 0.54 l and 0.89 l for forearms, and 11.82 l and 14.82 l for the two legs. However, when the performances of males and females were grouped by lean limb volume, it was found that while in both tests there were linear relationships, males and females did not share a common line. In both tests the male relationship was at a higher level than the female; therefore, for a given lean volume, the male performance was significantly superior to that of the female. The gender difference found in this study has not been seen in other studies in which the performance of skeletal muscle has been related to the cross-sectional area of the active muscles and the possible reasons for the differences are considered.

It has been suggested that guanethidine can release and then deplete postganglionic sympathetic nerve endings of noradrenaline. However, no release of noradrenaline from postganglionic nerve endings or from the adrenal medulla by guanethidine was found by direct experiment. Although release of noradrenaline from postganglionic sympathetic nerve endings in response to nerve stimulation was rapidly reduced and finally abolished by guanethidine, the drug did not appear to affect the release of catechol amines from the adrenal medulla in response to splanchnic nerve stimulation. The nature of the action of guanethidine is discussed, and it is concluded that it blocks the effect of postganglionic sympathetic nerve stimulation by interfering with the synthesis of transmitter and that it also has a direct sympathomimetic effect.Intravenous injection of guanethidine has three main effects in the anaesthetized cat. First, there is an initial rise of blood pressure followed by a slow fall; the control value is regained 0.5 to 2 hr later, and the pressure eventually settles somewhat lower. Second, the effect of postganglionic sympathetic nerve stimulation is abolished. Third, the blood pressure responses to intravenous injections of adrenaline and noradrenaline are potentiated.Although these actions have not been fully explained, it has been suggested that guanethidine releases transmitter from, and then depletes, the postganglionic sympathetic stores. The present experiments were designed to test this hypothesis. METHODSCats were anaesthetized with chloralose (80 mg/kg) after induction with ethyl chloride and ether. Femoral arterial blood pressure was recorded using a mercury manometer.Collection and assay of vasopressor activity in venous blood Spleen. The methods for stimulation of the splenic nerves and collection of blood samples were those of Brown & Gillespie (1957). Close-arterial injections into the spleen were made through a cannula in the stump of either the hepatic or the left gastric artery.Adrenal gland. The intestines and spleen were removed and the central end of the tied left renal vein was cannulated with polyethylene tubing. The left genital vein was tied. Blood from the left adrenolumbar vein was diverted into the cannula by an occlusion ligature proximal to the junction of the renal and adrenolumbar veins.