Giora Feuerstein

Renin-angiotensin mediation of adrenal catecholamine secretion induced by haemorrhage.

The mechanism involved in catecholamine (CA) release from cat adrenal gland, in response to haemorrhage was studied. In intact cats, in cats with bilateral cervical vagotomy or following bilateral ureteral ligation, haemorrhage induced an increased catecholamine release from the adrenal (with increased percentage of noradrenaline). Acute bilateral nephrectomy, chronic sodium loading with repeated administration of desoxycorticosterone acetate (DOCA), or acute denervation of the adrenal gland, completely abolished the increased CA release from the adrenal gland following haemorrhage. Haemorrhage induced an increase of plasma renin concentration in intact cats and after ureteral ligation but there was no increase in plasma renin after haemorrhage in cats with bilateral nephrectomy or following pretreatment with DOCA and salt load. Following haemorrhage in intact cats, blood pressure showed an immediate fall followed by rapid recovery. The recovery of blood pressure after haemorrhage was abolished in cats with bilateral nephrectomy. It is concluded that the adreno-medullary response to haemorrhage in the cat, depends primarily on the intact renal renin angiotensin system. Angiotensin, generated peripherally, probably affects the CNS and activates the sympathetic nerves.

Preferential secretion of adrenaline or noradrenaline by the cat adrenal in vivo in response to different stimuli

1 The concentrations of adrenaline and noradrenaline in the adrenal vein and the adrenal gland of the cat were studied in response to different stimuli leading to increased catecholamine (CA) secretion. 2 Haemorrhage and hypoglycaemia, but not acute exposure to cold or intravenous administration of cocaine, induced considerable increases in total catecholamine secretion. 3 The ratio of the concentration of adrenaline to noradrenaline in adrenal vein plasma during the control period was higher than the ratio in the adrenal gland itself. 4 Haemorrhage increased noradrenaline secretion considerably more than adrenaline secretion so that the ratio of the concentration of adrenaline to noradrenaline in adrenal vein plasma was significantly lower than in the adrenal gland itself. 5 Hypoglycaemia induced by insulin increased catecholamine secretion, with the adrenaline to noradrenaline ratio significantly higher than in the adrenal gland itself. 6 Hypothermia resulted in a fall of the initial high ratio of adrenaline to noradrenaline, to a value similar to that in the adrenal gland. 7 Neither cocaine nor changes in adrenal plasma flow affected the adrenaline to noradrenaline ratio in adrenal vein blood. 8 It is concluded that preferential release from the adrenal gland of either adrenaline or noradrenaline is possible in vivo in response to different stimuli.

Reversal by naloxone of hemorrhagic shock in anephric cats

Hemorrhage, 15 ml/kg induced a rapid fall of blood pressure in intact and anephric cats, but only intact cats demonstrated significant blood pressure recovery following bleeding. Naloxone, 0.1 mg/kg x min, i.v., had a mild promoting effect on blood pressure recovery in the intact cats whereas, in the hemorrhaged anephric cats naloxone re-established an almost complete recovery of blood pressure. These results suggest that endogenous opioid substances play a significant depressor role in hemorrhagic shock, especially in anephric animals.

Simultaneous changes of catecholamines and of Leu-enkephalin-like immunoreactivity in plasma and cerebrospinal fluid of cats undergoing acute hemorrhage

Cats, anesthetized with sodium pentobarbitone, underwent acute hemorrhagic shock by withdrawal of 15 ml blood/kg of body weight. The cerebral ventricular system was perfused with artificial cerebrospinal fluid (CSF). Blood and CSF samples were collected during 2 h, for the analysis of catecholamines (CA) and Leu-enkephalin-like immunoreactivity (LE-ir). The fall of blood pressure immediately after hemorrhage was accompanied by a rise of LE-ir in the CSF and by a decrease of norepinephrine and dopamine below their control values. About half an hour later, the LE-ir returned to its initial low level, while the CA were now markedly elevated. A similar opposite behavior of peptides and CA was observed during subsequent sampling periods, although blood pressure remained constant. These experiments demonstrate an inverse relationship of LE-ir and CA in the CSF, after acute hemorrhagic shock.

The effect of indomethacin on isoprenaline-induced renin secretion in the cat.

In vivo isoprenaline infusion (0.1 micrograms/kg.min)) into the renal artery of unilaterally nephrectomized cats elicited a 5-fold increase in plasma renin concentration (PRC). This increase was suppressed by concomitant administration of propranolol (0.3 mg/kg.min). Indomethacin (250 micrograms/kg.min) intrarenally infused prior to the administration of isoprenaline, abolished the isoprenaline-induced increase in PRC. It is suggested that prostaglandins mediate beta-adrenergic-activated renin release.

RENIN-ANGIOTENSIN MEDIATION OF ADRENAL CATECHOLAMINE SECRETION INDUCED BY HYPOGLYCAEMIA IN THE CAT

1 The mechanism involved in catecholamine (CA) release from the cat adrenal gland in response to insulin hypoglycaemia was studied. In intact cats, hypoglycaemia induced an 11 fold increase in adrenomedullary CA secretion. 2 Acute bilateral nephrectomy nearly abolished the increased CA release from the adrenal gland during hypoglycaemia. 3 Infusion of Sar1‐Ileu8‐Angiotensin II (AII), a competitive AII antagonist, suppressed the adrenomedullary response to the insulin‐induced hypoglycaemia. After termination of the antagonist infusion, CA secretion from the adrenal medulla increased rapidly, reaching the same level as in insulin‐treated cats. 4 Infusion of rabbit anti‐angiotensin I antibodies suppressed CA release from the adrenal gland of hypoglycaemic cats. This effect was more prolonged than that of Sar1‐Ileu8‐AII. 5 These results indicate that CA release from the adrenal medulla of the cat in response to insulin‐induced hypoglycaemia, is mediated through the renal reninangiotensin system. Since hypoglycaemia causes sympathetic stimulation through a central mechanism, angiotensin may act through the central nervous system.

Endogenous prostaglandins modulate adrenal catecholamine secretion

Adrenal catecholamine secretion induced by haemorrhage in the cat was increased by administration of indomethacin to intact or to bilaterally nephrectomized animals. Infusion of PGE2 (but not of PGF2 alpha) suppressed the increased catecholamine secretion caused by indomethacin.

Modification by SQ 14225 of blood pressure and adrenal catecholamine response to hemorrhage.

SQ 14225 infusion to cats exposed to hemorrhage suppressed adrenomedullary catecholamine release. The immediate compensatory blood pressure response was unaffected, while the later compensatory response was of a higher magnitude in intact cats that in SQ 14225-treated animals. Adrenal gland blood flow was better preserved in SQ 14225-treated hemorrhaged cats than in cats exposed to hemorrhage only. These data emphasize the role of angiotensin II in adrenal catecholamine and blood pressure responses to hemorrhage.

Selective reduction of adrenal medulla response to angiotensin induced by suppression of renin-angiotensin

Angiotensin II (AII) induced an increase of adrenaline (A) release from rat adrenal glands in vitro. The response of the adrenal glands was completely abolished 22--24 h after bilateral nephrectomy. Adrenal glands from DOCA-salt-treated rats did not respond to AII as well, whereas adrenal glands from rats treated with furosemide and a low salt diet retained this response. High potassium in the medium increased significantly the release of A from in vitro incubated adrenal glands of nephrectomized rats from 0.43 +/- 0.04 to 0.63 +/- 0.06 microgram/gland and salbutamol (in calcium-free medium) increased the release from 0.34 +/- 0.03 to 0.43 +/- 0.03 microgram/gland. These results indicate that the adrenal medulla develops subsensitivity to AII in vitro, following a reduction in levels of this agonist in vivo.

Attenuation of the Lithium-Induced Diabetes-Insipidus-Like Syndrome by Amiloride in Rats

The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.