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M Pickford

Publications and source records attributed to M Pickford.

35 records · Page 2Linked to original sources
PubMed1976

A search for the factors responsible for absence of recovery of the normal vascular response to oxytocin following sympathetic nerve injury.

In dogs following crush injury to the lumbar sympathetic trunk, reflex vasoconstriction reappears in 4-6 months but the normal vasodilator response to oxytocin does not return even 12 months after crush. Histochemical examination of the walls of the blood vessels shows that division or crush of the lumbar sympathetic trunk or removal of terminal ganglia leads to decentralization, not denervation of the blood vessels. True denervation follows division or crush of the sciatic and femoral nerves. Following recovery from sciatic or femoral crush the pattern of peripheral innervation appears histochemically normal. However, there is no return of the normal vasodilator response to oxytocin. It is concluded that a normal response to oxytocin does not return even after long-term recovery from sympathetic injury, nor does its effect depend on a normal pattern of peripheral adrenergic innervation, but on an unknown more central activity of the sympathetic nervous system.

Animals↗
PubMed1975

The distribution time of intravenously injected raffinose and inulin in intact animals and the effect thereon of sex and infusion of oxytocin.

1. In anaesthetized dogs whose renal pedicles were ligated the distribution time for I.V. administered raffinose was noted. In males the plasma concentration of raffinose fell for 7-10 min from the time of injection and in females it fell for 12-15 min; thereafter in both sexes the plasma concentration remained constant. 2. During I.V. infusion of oxytocin 10 mug/kg. min, the distribution time for raffinose was 12-16 min in males and 4-6 min in females. 3. During the period before stabilization of plasma concentration the concentration of raffinose was higher in the femoral artery than in the vein in both sexes. 4. In anaesthetized rats whose renal pedicles were ligated the distribution time for I.V. injected inulin was 7-8 min in males and 5 min in females. 5. Following alpha-adrenoceptor blockade with phentolamine the distribution time in both male and female rats was 14-15 min. 6. The sex differences in distribution time, both in normal and oxytocin-treated dogs, may be related to the state of contraction and differential sensitivity or pre- and post-capillary blood vessels and hence, of capillary pressure.

Animals↗
PubMed1971

Effects of angiotensin and noradrenaline on discharge in fibres of the cervical sympathetic nerve in cats and dogs.

1. The effects of angiotensin and noradrenaline on discharge frequency in single and few-fibre preparations of the cervical sympathetic nerve of cats and dogs have been compared.2. When equal changes in blood pressure were produced by intravenous infusion of these drugs, the changes found in sympathetic discharge were similar both in anaesthetized animals and in a decerebrate one.3. Angiotensin and noradrenaline also have similar effects on discharge in sympathetic nerve fibres following complete denervation of the baroreceptor and chemoreceptor nerves.4. It is concluded that when the blood pressure is raised to 200 mmHg by angiotensin, the drug has no central stimulant action on the sympathetic nervous system.

Angiotensin II↗
PubMed1971

Effect of catecholamines and angiotensin on extracellular water and cation movements and the effect of alpha and beta-adrenoceptor blockade.

1. The extracellular fluid volume (ECFV), as raffinose space, and its content of Na, K and Ca were measured in anaesthetized dogs in acute experiments before and during the vascular response to intravenous injections and infusions of noradrenaline, adrenaline, isoprenaline and angiotensin.2. In male dogs the effect of noradrenaline was unpredictable, the ECFV might increase or decrease. In female dogs noradrenaline caused an increase in the ECFV. The difference between the responses of the two sexes was statistically significant (P<0.001). After phentolamine, noradrenaline exerted no effect at all in either sex. After bretylium the results were like those in normal animals.3. In both males and females adrenaline generally induced an increase in the ECFV. After phentolamine, adrenaline decreased the ECFV in males and caused little change in females. The differences before and after blockade were statistically significant (P<0.001). After bretylium the results in both sexes were like those in normal animals.4. In both male and female dogs isoprenaline induced an increase in the ECFV and the results were the same as in the normal animals after both phentolamine and bretylium.5. In male dogs there was no change in the ECFV as a result of administering angiotensin, either alone or in the presence of phentolamine or bretylium. In normal females angiotensin induced a decrease in ECFV and the difference between the responses of the males and females was statistically significant (P<0.005). In females which had received either phentolamine or bretylium the results were indistinguishable from those in the males.6. Blockade of the beta-adrenoceptors with pronethalol in a few animals did not change the response to the drugs from those seen in normal animals.7. The cation content of the ECF changed in the same direction and to about the same extent as the water, except after noradrenaline when in some experiments the proportionate change in potassium concentration was considerably greater than that of the other substances.8. The inulin space and its Na and K content were measured in several dioestrous, oestrous and pro-oestrous rats and in normal and stilboestrol treated males before and after giving an intravenous injection of angiotensin. There was little difference between the results of control injections of 0.9% saline solution and of angiotensin in dioestrous and oestrous females and normal males. On the other hand, pro-oestrous females and stilboestrol treated males responded alike to angiotensin in the form of a decrease in ECFV which was statistically different from the responses in the other three groups (P<0.0005).9. It is suggested that the various results depend on two factors: the site of action of the drug-for example, whether it increases or decreases capillary pressure and therefore, fluid transfer-and also the sex of the animal. The ground substance of the small blood vessels is probably important in taking up and releasing fluid, and its capacity for so doing may well vary with the amount of available oestrogen. It appears that the effect of oestrogens and events at the alpha-adrenoceptor site are connected in some way.

Adrenergic alpha-Antagonists↗
PubMed1971

Sex differences in the changes in sympathetic nerve activity when arterial pressure is raised by infusion of angiotensin and noradrenaline.

1. In cats and dogs impulse frequency was studied in single and few-fibre preparations of the cervical sympathetic nerves when blood pressure was raised in steps to about 200 mm Hg by infusions of noradrenaline and angiotensin. Two forms of frequency/blood pressure relationships were found which differed in their distribution between the sexes.2. In females, both normal and ovariectomized, there was an inverse linear relationship between spike frequency and blood pressure over the whole range of blood pressure studied. The same was true in castrated males and normal males pretreated with oestrogens.3. In normal males the inverse linear relationship held to a pressure of about 150 mm Hg. At higher pressures the sympathetic discharge rate remained steady or increased. This was also found in castrated males pretreated with testosterone. There was a statistically significant difference between the responses of these animals and those of normal females and castrated or oestrogen treated males.4. The sex difference originates peripherally since the responses of both sexes were similar following baroreceptor and chemoreceptor denervation. During ventilation with oxygen instead of air the male pattern of response becomes like that of the female. The latter observation implicated the chemoreceptors.5. alpha adrenoceptor blockade with phenoxybenzamine and phentolamine localized to the region of the carotid bifurcation in male cats abolished the increase in sympathetic discharge rate at high blood pressure induced by noradrenaline, but did not alter the response to angiotensin.6. Records of spike frequency in single and few-fibre preparations of chemoreceptor units in the sinus nerves of cats also showed an inverse relationship between frequency and blood pressure in females. In males at the higher pressures, the discharge rate was steady or increased. The increased chemoreceptor discharge at high pressures in males was abolished by ventilation with oxygen instead of air.7. The sex difference in behaviour of chemoreceptor units could not be explained by differences in either total carotid body blood flow or arterial oxygen tension.8. It is tentatively concluded that the observed sex difference is related to the state of the blood supply to the chemoreceptors and that, in males, testosterone sensitizes the blood vessels to vasoconstrictors, so that at high pressures blood is diverted through shunts and the chemoreceptors are subjected to a stagnant hypoxia.

Angiotensin II↗
PubMed1968

The effect of oestrogen and progesterone on the pressor action of angiotensin in the rat.

1. A comparison was made between the pressor responses to angiotensin in rats during different stages of the oestrous cycle, pregnancy, pseudopregnancy and also following oestrogen and progesterone treatment.2. No evidence for an effect of oestrogen on the response to angiotensin was found.3. Pregnancy and pseudopregnancy were found to diminish the pressor response to angiotensin.4. Progesterone treatment also diminished the response to angiotensin.5. It is suggested that the decrease in pressor response in pregnancy and pseudopregnancy is attributable to progesterone.6. The possible mode of action of progesterone is discussed.

Angiotensin II↗
PubMed1967

The effect of oxytocin and adrenaline on blood flow in the hind limb of the dog following chronic lumbar sympathectomy.

1. In a number of dogs the last two lumbar ganglia were removed unilaterally. At various dates up to the 56th day after operation the dogs were anaesthetized and the effect of oxytocin and adrenaline on hind-leg blood flow studied. Oxytocin alone reduced leg flow in all dogs after operation.2. Until approximately day 11 after operation oxytocin given during an infusion of adrenaline increased leg blood flow, as it does in normal dogs not given adrenaline infusion. After that date it reduced the flow even during adrenaline infusion. The timing of this change suggests that the normal response to adrenaline depends on the presence of undegenerated nerve fibres.3. In one animal the sympathetic nerves were crushed between the last two lumbar ganglia and beyond the last, and hind-leg blood flow frequently measured by means of venous occlusion plethysmography until day 204, when the animal was anaesthetized and acute observations made. Electrical stimulation of the sympathetic chain above the site of crushing caused a reduction in leg flow, indicating that at least some of the nerve supply had regenerated. However, oxytocin reduced leg flow when used alone and exerted no apparent effect in the presence of adrenaline.4. It is suggested that sympathetic nerves to vascular smooth muscle have a function or functions other than transmitter release and that when crushed nerves regenerate the functions do not recover at the same rate.

Animals↗
PubMed1967

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.

Journal Article↗