Yehuda Gutman

Regulation of food and water intake in rats as related to plasma osmolarity and volume

Abstract Food intake was suppressed in rats by subcutaneous injection of hypertonic saline while intraperitoneal loading of isotonic saline increased food consumption. Hypovolemia induced by subcutaneous injection of polyethylene glycol (Carbowax, M-20), decreased food intake in rats considerably. Free access to water under food deprivation caused significant dilution of plasma while free access to food under water deprivation resulted in hypertonicity of plasma. Feeding schedules of 23 hr food and 1 hr water vs 23 hr water and 1 hr food, caused plasma osmolarity to change from 286 mOsm/kg to 318 mOsm/kg. These wide variations are discussed in relation to the interaction of plasma osmolarity with food and water intake.

Polydipsia induced by isoprenaline and by lithium: Relation to kidneys and renin☆

Abstract Water intake in rats was increased by the administration of either isoprenaline or LiCl. The polydipsia induced by both drugs was completely abolished following bilateral nephrectomy. Bilateral ligature of the ureters did not eliminate the isoprenaline-induced drinking but decreased considerably the effect of lithium on water intake. Water intake after bilateral ligature of the ureters was significantly larger than that following bilateral nephrectomy. Isoprenaline and LiCl significantly increased plasma renin activity. Propranolol abolished both the rise of plasma renin activity and the polydipsia caused by isoprenaline. Renin, injected into rats, increased significantly their water intake. It is suggested that the polydipsia caused by isoprenaline and by lithium chloride is mediated through the release of renin.

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.

The differential effect of Li + on microsomal ATPase in cortex, medulla and papilla of the rat kidney.

Abstract 1. 1. The effect of Li + on microsomal ATPase was studied in the cortex, medulla and papilla of the rat kidney. 2. 2. At Li + concentrations, in vitro , of 5–50 mM no significant effect on Mg 2+ -ATPase activity in any part of the kidney was observed. At concentrations of 100–150 mM a slight inhibition of the activity of this enzyme was found. 3. 3. At in vitro Li + concentrations of 5–50 mM (Na + + K + )-dependent ATPase was found only at 10 mM LiCL. At a concentrations of 150 mM Li + inhibited (Na + + K + -dependent activity in the medulla and cortex. 4. 4. In vivo administration of LiCl at a dose of 2 mequiv/kg daily for 14 days caused a significant increase in (Na + + K + )-dependent ATPase in the medulla and papilla but not in the cortex of the kidney. 5. 5. The significance of these findings with respect to the clinical effect of Li + is discussed. 6. 6. The experiments reported demonstrate a selective effect of Li + on (Na + + K + -dependent ATPase in the kidney medulla as compared to this enzyme in the kidney cortex.

EFFECTS OF VERAPAMIL, DANTROLENE AND LANTHANUM ON CATECHOLAMINE RELEASE FROM RAT ADRENAL MEDULLA

1 The release of catecholamines (CA) from rat adrenal incubated in vitro in Locke solution was studied. 2 Acetylcholine‐induced release of CA and CA release by 56 mm KC1 were inhibited by verapamil and lanthanum chloride which block calcium permeability. 3 CA secretion induced by salbutamol or by theophylline was unaffected by either verapamil or lanthanum chloride. 4 Dantrolene‐sodium inhibited the CA secretion induced by theophylline but only partially reduced potassium‐induced release of CA. 5 Verapamil enhanced the secretion of CA induced by salbutamol (in a calcium‐free medium). 6 Tyramine‐induced secretion of CA was unaffected by lanthanum chloride, verapamil or dantrolene‐sodium. 7 It is suggested that cyclic adenosine 3′,5′‐monophosphate‐mediated CA secretion (induced by theophylline or salbutamol) depends on release of calcium from intracellular stores, and that CA secretion induced by tyramine is independent of intra‐ or extracellular calcium.

α-Adrenergic stimulants, prostaglandins and catecholamine release from the adrenal gland in vitro

In rat adrenal glands incubated in Lockes solution in vitro norepinephrine and phenylephrine inhibited the release of epinephrine. PGE2 and PGE1 also inhibited the release of catecholamines but PGFalpha1 had no effect on the adrenal. Thus, catecholamine release from adrenal cells may be regulated by the same mechanisms as in adrenergic nerve endings.

Angiotensin increases microsomal (Na+−K+-ATPase activity in several tissues

Abstract Angiotensin increased microsomal (Na + K + )-activated ATPase from rat hypothalamus, mucosa of colon and bovine adrenal cortex but not brain cortex. Angiotensin did not change significantly Mg 2+ -ATPase in these tissues. Enhancement by angiotensin was evident at concentrations of 10 −8 − 10 −12 M. In bovine adrenal cortex angiotensin increased ATPase activity in the outer and not in the inner layer. Angiotensin increased ATPase activity with Na + above 20 mM and K + above 5 mM present simultaneously, but not with either ion alone.

The effect of urea, sodium and calcium on microsomal ATPase activity in different parts of the kidney

Abstract Mg 2+ -ATPase and (Na + + K + )-dependent ATPase activities were assayed in the microsomal fractions of the cortex, medulla and papilla of the guinea-pig kidney. Mg 2+ -ATPase in any part of the kidney was unchanged in the presence of 300 mM urea. (Na + + K + )-dependent ATPase activity was unchanged in the cortex, but was significantly inhibited in the medulla and papilla by 300 mM urea. Elevated concentrations of Na + (200 mM) depressed ATPase activity in the microsomal fraction derived from the papilla and medulla, but did not significantly affect the activity in the kidney cortex. Ca 2+ (5 mM) caused a significant inhibition of (Na + + K + )-dependent ATPase in all three parts of the kidney and depressed Mg 2+ -ATPase activity only in the papilla.

Suppression by noradrenaline of catecholamine secretion from adrenal medulla

Abstract The release of catecholamines from the rat adrenal medulla caused by insulin-hypoglycemia was blocked by noradrenaline without affecting hypoglycemia. It is suggested that release of catecholamines from the adrenal cells may be regulated by α-adrenoceptors, similar to the mechanism described for adrenergic nerve endings.