An examination of certain factors which might, or do, affect the vascular response to oxytocin.

1. A number of different observations were made on anaesthetized rats and some dogs to try to discover why it is that oxytocin is a vasodilator in dioestrus and anoestrus, and develops constrictor properties in oestrus and following sympathectomy.2. In those circumstances in which oxytocin in small or moderate doses raises blood pressure in the rat, the pressor effect is eliminated if the hormone is given during an infusion of adrenaline. In this respect the rat is closely similar to the dog.3. It was confirmed in anaesthetized oestrous rats that intravenous eserine eliminated the pressor response to oxytocin, and it was found that prostigmine did not reduce or change it. Thus, it may be concluded that the effect of eserine depends on its central sympathetic stimulant action and not on a peripheral effect.4. Rats which had been acutely or chronically adrenalectomized responded normally to oxytocin and both eserine and adrenaline were able to reduce, though not wholly eliminate, the pressor type of response. These results indicate that neither the adrenal medulla nor the cortex is essential for the action of oxytocin, nor for a large part of the action of eserine and adrenaline.5. The plasma concentrations of sodium, potassium and calcium were studied in a number of conditions affecting the response to oxytocin, namely, dioestrus, oestrus, and after administration of oestrogens, progesterone, adrenaline, eserine, hexamethonium, and dihydroergotamine. The cation changes observed could not be correlated with the type of response to oxytocin. The only measure found to affect the response was raising the plasma Na concentration by the infusion of disodium hydrogen phosphate. This reduced the pressor effect of oxytocin seen in oestrous female rats and in oestrogen treated males. The pressor response returned before the plasma sodium had fallen to normal levels.6. The administration of the oxytocin analogue, tyrosine-methyl(2) oxytocin which has a high receptor affinity and a low intrinsic activity, prevented the pressor response to oxytocin of oestrous rats, and the vasodilator response in the hind limb vessels of normal dogs. It is concluded that there is probably a single receptor for oxytocin from which both the constrictor and dilator effects are initiated.7. Oxytocin exerted apparently normal effects on the systemic blood pressure of oestrous or dioestrous rats given the beta-blocking agents pronethalol or propranolol.8. The present results, like previous ones, indicate that adrenaline is the factor linking both the gonadal state and the peripheral sympathetic nervous system with the type of response to oxytocin.9. An incidental observation was that male and female rats show differences in their response to sympathetic blocking agents and to a raised plasma sodium concentration.