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1 The effect of alpha-adrenoceptor agonists on membrane adenosine triphosphatase (ATPase) activity was studied in membranes from the bovine adrenal medulla and the rat submaxillary gland. 2 alpha-Adrenoceptor agonists (10(-7) to 10(-5) M) enhanced significantly Na,K-ATPase activity but not Mg-ATPase activity in adrenal medulla. This effect was not observed in membranes from phaeochromyocytoma. Phenylephrine (10(-5) M), naphazoline (10(-5) M) and clonidine (10(-5) M) caused a significant increase of the activity of Na,K-ATPase (but not of Mg-ATPase) in the submaxillary gland. The enhancement became more prominent after ligature of the submaxillary duct but disappeared completely after superior cervical ganglionectomy. Thus, the effect of the alpha-adrenoceptor agonists was due to an action on adrenergic nerve terminals in the submaxillary gland. 3 Phenylephrine and naphazoline did not affect 45Ca uptake but enhanced the rate of 45Ca efflux from adrenal medullary slices in vitro. 4 Phenylephrine enhanced the rate of 45Ca efflux from slices of submaxillary gland (with previous ligation of the duct); this was blocked by phentolamine and sympathetic denervation. Therefore phenylephrine was acting on the adrenergic nerve terminals. 5 It is suggested that the inhibition by alpha-adrenoceptor agonists of the exocytotic release of catecholamines from adrenergic nerve terminals and from chromaffin cells may be due to activation of the sodium pump, which results in enhancement of calcium efflux, causing a reduction of free intracellular Ca2+.

Prostaglandin E2 induced increased catecholamine release in vitro from adrenals of hypophysectomized rats, while in adrenals of intact rats catecholamine release was suppressed by prostaglandin E2.

Hypertension was induced in rats (Hebrew University strain) by three different procedures: (1) deoxycorticosterone acetate (DOCA)--salt treatment; (2) unilateral renal artery clip or (3) chronic salt-loading. Noradrenaline (NA) and dopamine (DA) distribution in different brain areas was assayed following induction of hypertension. NA content increased significantly in various areas: the increase of NA in the pons-medulla was common to all procedures inducing hypertension. NA content increased also in the mesencephalon, the hypothalamus and the rest of the forebrain (DOCA--salt hypertension), in the mesencephalon, the hypothalamus and the cortex (in renal clip hypertension). No significant changes in DA content were observed in any region of the brain following induction of hypertension by the three different methods. In two substrains, selected from the Hebrew University strain, for their respective sensitivity (H) or immunity (N) to hypertension induced by DOCA--salt treatment, there were no significant increases in NA or DA in any part of the brain following DOCA--salt treatment. Comparison of NA concentrations in these strains showed that NA was significantly higher in the pons-medulla of the untreated N strain rats than in the medulla of untreated H strain or in untreated rats of the original strain (Hebrew University). A model is presented suggesting that central NA-containing neurons plays a major role in controlling hypertension.

Catecholamine (CA) secretion from the adrenal medulla was induced in vitro by acetylcholine (10(-4)M) (ACh), by incubation in potassium-free medium, by addition of ouabain (10(-3)M), by theophylline (10(-2)M) or by salbutamol (10(-6) and 6 x 10(-6) M). Theophylline and salbutamol, but not ACh, released CA in a calcium-free medium supplemented with 2mM EGTA. PGE2 significantly inhibited both CA secretion evoked by ACh and that evoked by salbutamol, i.e. both secretion dependent on, and independent of, extracellular calcium, PGE2 counteracted the increase of cAMP levels caused by ACh or salbutamol in adrenal medullary slices. PGE2 also diminished the salbutamol-induced activation of adenylate cyclase in an adrenal medullary membrane preparation, PGE2 reduced the rate of 45Ca efflux from slices of adrenal medulla preloaded with 45CaCl2. It is suggested that PGE2 inhibits CA secretion through the following sequence: inhibition of adenylate cyclase, a fall of cellular cAMP resulting in reduced release of calcium from intracellular binding sites and reduced free cytoplasmic calcium.

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.

The release of catecholamines from human adrenal was studied by in vitro incubation of slices. Catecholamine release was significantly inhibited by the addition of either phenylephrine (10(-5) M) or PGE2 (10(-7) M) to the incubation medium. The similarity of these modulating actions to those found in rat adrenal is discussed.

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.

By means of a microinjection technique, inulin-carboxyl-C(14) or inulin-methoxy-H(3) was injected into single proximal tubules of the rat at various urine flow rates. Urine collected separately from the two kidneys showed negligible amounts of inulin activity on the noninjected side, thus demonstrating directly that there is no significant reabsorption of inulin by the renal tubular epithelium under these conditions.