The effects of infusions of synthetic adrenocorticotrophin in the conscious calf

SUMMARY1. Right medullary and various cardiovascular responses to stimulation of the peripheral end of the splanchnic nerve have been investigated in the presence and absence of exogenous adrenocorticotrophin, ACTH1 24, (5 ng min-kg-'). The adrenal-clamp technique was employed in conscious calves, after the pituitary stalk had been cauterized and they had recovered from anaesthesia.2. The intravenous infusion ofACTH1 24increased the plasma ACTH concentration by about 1100 pg ml-' and right adrenal venous output of cortisol by about 400 ng min' kg body weight-'. Stimulation of the splanchnic nerve at 4 Hz for 10 min had no effect on either arterial plasma ACTH concentration or the adrenal output of cortisol.3. Closely similar amounts of both adrenaline and noradrenaline were released in response to nerve stimulation in the presence and absence of exogenous ACTH. In contrast, the fall in adrenal vascular resistance of about 40 %, which normally occurred in response to splanchnic nerve stimulation, was completely abolished by ACTH.4. The adrenal produced relatively large quantities of met-enkephalin-containing peptides. During splanchnic nerve stimulation the output of these increased 20-100-fold, at which time free met5-enkephalin accounted for only 10-20 o of total. During ACTH infusion the output of free met5-enkephalin was reduced at rest and during nerve stimulation, but that of total met-enkephalin-containing peptides was unaffected. These results indicate that ACTH or an adrenal steroid may alter the processing of proenkephalin in the adrenal medulla acutely but not total opiate secretion. Alternatively, the presence ofACTH could act by influencing the population of chromaffin cells activated by splanchnic nerve stimulation.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of synthetic adrenocorticotrophin on adrenal medullary responses to splanchnic nerve stimulation in conscious calves.

Edwards¹,

Hansell²,

Jones³

1986

“…Intravenous infusions of synthetic adrenocorticotrophin at a dose of 5 0 ng. kg-1 min-produced a substantial increase in the output of both cortisol and corticosterone from the right adrenal, together with a significant rise in blood flow through the gland (Edwards, Hardy & Malinowska, 1974).…”

Section: Introductionmentioning

confidence: 99%

The sensitivity of adrenal responses to synthetic adrenocorticotrophin in the conscious unrestrained calf.

Edwards¹,

Hardy²,

Malinowska³

1975

SUMABRY1. Changes in cortisol and corticosterone output and blood flow from the adrenal gland have been determined in the conscious unrestrained calf during i.v. infusions of synthetic adrenocorticotrophin (Synacthen) at 0 5 ng . kg-' min-' (low dose), 5 ng . kg-' min-' (medium dose), 50 ng . kg-' min-' (high dose) and 500 ng.kg-' min-' (very high dose).2. Infusions at the low dose produced a rise in adrenal output of both cortisol and corticosterone to maximum values of approximately 100 and 30 ng. kg-' min-L respectively. Mean output of both steroids was significantly increased within 5 min, reached a maximum within 10 min and had fallen to resting levels 10 min after the infusion was discontinued.3. The effects of infusions at both the high and very high doses were closely similar; maximal cortisol outputs were within the range 600-800 ng . kg. -' min-' and corticosterone 350-500 ng . kg-' min-' in both groups.4. When the infusions were terminated, pronounced differences were observed in the rates at which steroid outputs declined. Basal levels were restored within 10 min following the low dose and within 60 min in medium dose animals, but both cortisol and corticosterone output were still elevated 2 hr after infusion in high dose animals. In calves infused at the very high dose, cortisol output did not fall significantly during this 2 hr period.5. The ratio of cortisol: corticosterone released from the adrenal gland immediately before infusion (3.2 + 0 3) approximated to the proportions in which the two steroids were found in the arterial plasma, but fell progressively to a minimum (1.3 + 0.1) with increasing doses of Synacthen. Conversely, the ratio of the steroids in the arterial plasma was increased during infusions at the low dose, but not at the higher doses. 6. No significant change in adrenal blood flow occurred during Synacthen infusion in low dose animals despite the increase in steroid output. In A. V. EDWARDS AND OTHERS medium dose animals blood flow through the gland rose during infusion by approximately 75 % while in both high and very high dose animals the flow increased by up to 300 %.7. In the three groups in which adrenal hyperaemia occurred, blood flow had fallen to within the resting range 45 min after infusion: in each case this fall was much more rapid than the fall in steroid output. No significant increase in aortic blood pressure or heart rate accompanied infusion of Synacthen, indicating that adrenal hyperaemia was dependent upon vasodilatation within the gland.8. Administration of cycloheximide (10 mg/kg) by i.v. injection either before or during an infusion of Synacthen, inhibited steroidogenesis without affecting the vasodilator response.

“…The catheter with the tip in the thorax was employed for intra-aortic infusions of acetylcholine above the level of the adrenal gland. The right kidney was removed, the right renal vein was cannulated and an adrenal clamp emplaced (Edwards, Hardy & Malinowska, 1974;Edwards, Furness & Helle, 1980). The right splanchnic nerve was cut immediately below the diaphragm and a Braunula cannula inserted into the jugular vein to provide a conduit for i.v.…”

Section: Experiments Proceduresmentioning

confidence: 99%

Muscarinic adrenal responses to acetylcholine in conscious calves.

Jones

Edwards

1991

SUMMARY1. Adrenal responses to intra-aortic infusions of acetylcholine (4-5 nmol min-' kg-' for 10 min) have been investigated in hypophysectomized conscious calves given exogenous adrenocorticotrophic hormone (ACTH) (2 ng min-' kg-' i.v.) in the presence and absence of hexamethonium.2. Acetylcholine produced a significant increase in adrenal cortisol output and plasma cortisol concentration. In the absence of nicotinic blockade with hexamethonium this was apparently accounted for by an increase in adrenal ACTH presentation secondary to increased adrenal blood flow. However, administration of hexamethonium revealed a direct steroidogenic action of acetylcholine in the presence of exogenous ACTH 3. Adrenal medullary responses to acetylcholine, including the release of catecholamines, enkephalins and corticotrophin-releasing factor (CRF), were not significantly reduced by nicotinic blockade.4. It is concluded that both adrenal medullary and cortical responses to intraaortic infusions of acetylcholine at a low dose are mediated mainly by muscarinic receptors, as it has previously been shown that they are substantially reduced in the presence of atropine.