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Why are circulating concentrations of endothelin-1 so low?

Physiological and pathophysiological roles of endothelins are still unclear. One reason is that circulating endothelin levels in normal and pathological states are much lower than the concentrations necessary to elicit contractions in vitro. It is usually assumed that endothelin accumulates in diseased tissues and that, because of its degradation, only a small fraction of it reaches the systemic circulation. Such a hypothesis does not fit with recent observations showing that low circulating endothelin levels may be active. We show here that most of the current inferences about the actions of endothelin assume that the peptide acts in the vessel wall under conditions known as non-stoichiometric binding conditions, that is, under conditions in which the receptor concentration in tissues ([Ro]) is smaller than the equilibrium dissociation constant of endothelin receptor complexes (Kd). Under stoichiometric binding conditions (defined by the condition [Ro] > Kd), most ligand molecules are bound to receptors and cannot be present in a free form. Estimates of [Ro] and Kd from the literature suggests that in vivo endothelin probably binds stoichiometrically to its receptors. Under this condition, most of tissue endothelin is probably bound to receptors. It is therefore suggested that plasma endothelin levels are low probably because tissue free endothelin levels are low, and this is not inconsistent with the presence of high tissue levels of active (that is, bound) endothelin. When the topology of the vessels with respect to the site of production (or of delivery) of endothelin is considered, stoichiometric binding may also account for the higher sensitivity to Et-1 of in vivo preparations. It also suggests that autocrine and paracrine actions of Et-1 are favoured at low and high secretory rates respectively, thus providing an explanation for the dual (vasodilator and vasoconstricting) actions of endothelin. Finally, the stoichiometric binding model predicts that functional receptors also act as clearance receptors and provides an explanation for the observation that antagonists of endothelin receptors are also clearance antagonists.

Endothelins↗

Phospholipase A2 activity in salivary glands and saliva of the lone star tick (Acari: Ixodidae) during tick feeding.

Phospholipase A2 (PLA2) activity levels in tick [Amblyomma americanum (L.)] salivary glands and saliva were examined during tick feeding by using 14C-phosphatidylcholine as the substrate. Saliva produced by stimulating female ticks to salivate with dopamine contains PLA2 (ts-PLA2) activity. The ts-PLA2 activity level in saliva did not change significantly during tick feeding except for a decrease in the last rapid feeding phase (> 200 mg) and in replete ticks. Phospholipase A2 activity was higher in salivary glands of fed than unfed ticks, both in males and females; activity increased during tick feeding correlating with salivary secretory rates during tick feeding suggesting that much of the PLA2 activity measured in whole salivary glands is synthesized for subsequent secretion. During the time course of in vitro salivation, the first 10 microliters of saliva contained higher ts-PLA2 activity than saliva secreted thereafter. Phospolipase A2 was identified in the saliva of artificially fed ticks indicating that ts-PLA2 is a physiological component of tick saliva.

Animals↗

Low protein diets potentiate lithocholic acid-induced cholestasis in rats.

Earlier studies showed that low protein diets (LPD) reduce bile flow and bile acid secretion. We therefore examined the effect of LPD on lithocholic acid (LCA)-induced intrahepatic cholestasis. Female Sprague-Dawley rats were fed LPD (8% casein) soon after weaning for 4 or 12 wk, and then were injected intravenously with a single dose of LCA (4 mumol/100 g body wt). Bile was collected for 30-min periods, and bile flow as well as biliary lipid secretory rates were measured. Bile acid metabolism was also studied and the results were compared with those obtained in rats fed an adequate protein diet (26% casein). The LPD produced significantly lower bile flow and bile acid secretion, which were attributed to a reduced bile acid pool and a reduction in synthesis. They also enhanced the LCA-induced decline in bile flow, and rate of biliary output of total bile acids, phospholipids and cholesterol. The LPD were also associated with impaired LCA secretion in bile and increased retention in plasma and liver. Studies of LCA metabolism in rats fed a LPD indicated lower hepatic LCA hydroxylation, a greater percent contribution of glyco conjugates and lower levels of tauro conjugates. The present findings suggest that the reduced bile acid pool size, diminished LCA excretion and biotransformation to less toxic bile acids may explain the greater cholestasis in LPD-fed rats.

Animals↗

Early pregnancy wastage following late implantation of embryos after in-vitro fertilization and embryo transfer.

Serial plasma concentrations of human chorionic gonadotrophin (HCG), progesterone and oestradiol were measured in pregnancies after in-vitro fertilization and embryo transfer. The first detection day of HCG after embryo transfer (8.4 +/- 1.1) and the HCG doubling time (DT) of 64 normal singleton pregnancies were compared to those of 14 first-trimester miscarriages. The same parameters were evaluated in nine late-implanted conceptions, seven of which resulted in early pregnancy wastage. The HCG DT of late-implanted pregnancies was consistent with that of singleton term pregnancies in the first 12 days, while first-trimester miscarriages which had implanted at the usual time had a significantly longer DT from implantation onwards. The reduced trophoblastic secretory rate suggests poor embryo quality in these cases. A decreased progesterone/oestradiol ratio was observed in late-implanted pregnancies but because of the small number of individuals, no definite conclusion can be drawn. More patients with delayed implantation should be tested to justify this observation.

Adult↗

Effects of gonadectomy and steroids on pituitary gonadotropin secretion in a frog, Rana pipiens.

Secretory dynamics of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured at various times following gonadectomy in adult male grass frogs, Rana pipiens. Plasma levels and in vitro initial secretory rates of both LH and FSH increased significantly within 1 wk and remained elevated for 3-4 wk of castration. Pituitary FSH and LH content were unchanged. However, dissociation between the two gonadotropins (Gth) occurred thereafter: Secretion of FSH remained elevated for 70 days, but those of LH declined to control levels after 30 days. In vitro secretion of Gth from gonadectomized (gonadx) frogs declined progressively over time reaching control levels after 24 h incubation. The results indicate that elevated pituitary secretion contributes to the observed circulating LH and FSH levels in gonadx frogs, and that FSH and LH may be controlled independently. Replacement therapy with 17 beta-estradiol (E2) suppressed post-gonadectomy increases in plasma Gth and in vitro responses to GnRH, whereas 5 alpha-dihydrotestosterone (DHT) had little effect in vivo and augmented GnRH responses in long-term castrates. In vitro, E2 also inhibited, while 48 h of DHT treatment had no effect on GnRH responsiveness of pituitaries from gonadx frogs. The actions of these steroids were opposite to those typically observed in mammals (and birds), and support the hypothesis that E2 may contribute to seasonal testicular regression in ranid frogs.

Androgens↗

Slow spontaneous secretion from single large dense-core vesicles monitored in neuroendocrine cells.

Hormones are released from cells by passing through an exocytotic pore that forms after vesicle and plasma membrane fusion. In stimulated exocytosis vesicle content is discharged swiftly. Although rapid vesicle discharge has also been proposed to mediate basal secretion, this has not been studied directly. We investigated basal hormone release by preloading fluorescent peptides into single vesicles. The hormone discharge, monitored with confocal microscopy, was compared with the simultaneous loading of vesicle by FM styryl dye. In stimulated vesicles FM 4-64 (4 microM), loading and hormone discharge occurs within seconds. In contrast, in approximately 50% of spontaneously releasing vesicles, the vesicle content discharge and the FM 4-64 loading were slow (approximately 3 min). These results show that in peptide secreting neuroendocrine cells the elementary vesicle content discharge differs in basal and in stimulated exocytosis. It is proposed that the view dating back for some decades, which is that, at rest, the vesicle discharge of hormones and neurotransmitters is similar to that occurring after stimulation, needs to be extended. In addition to the classical paradigm that secretory capacity of a cell is determined by controlling the probability of occurrence of elementary exocytotic events, one will have to consider activity modulation of elementary exocytotic events as well.

Animals↗

A porspective study of parietal cell vagotomy and selective vagotomy-antrectomy for treatment of duodenal ulcer.

A prospective, randomized, study involving 92 patients who required elective operation for treatment of duodenal ulcer was performed to compare the results of Parietal Cell Vagotomy (PCV) and selective vagotomy-antrectomy Billroth I (SV-A-BI). The protocol was broken twice. One patient was unable to undergo PCV because of pyloric stenosis and one patients underwent Billroth II anastomosis instead of Billroth I because of post-bulbar stenosis. Performance of PCV was never aborted because a patient was obese. There were no deaths. Diarrhea, dumping and other gastric complaints were less frequent after PCV than after SV-A-BI for all time periods studies up to two years. Two months after operation, the Hollander tests were negative in 59% of patients after PCV and in 100% after SV-ABI. Inhibition of Bao and MAO were also significantly less after PCV than after SV-A-BI. Since vagotomy of the parietal cell mass was identical in both groups of patients it was concluded that the differences in the secretory rates and the fewer negative Hollander tests in the PCV group than in the SV-A-BI group were due to retention of the antrum irrespective of its innervation. There was no explanation for the gradual increase in the BAO in the PCV group. One recurrent ulcer occurred in the PCV group in a patient who overindulged in alcohol and aspirin. After 4 days of medical management, this superficial ulcer healed as demonstrated by endoscopy. There were no recurrent ulcers after SV-A-BI. As a result of this study, it is concluded that PCV is superior to SV-A-BI because of the lower frequency of postoperative complications, diarrhea, dumping and other symptoms associated with gastric surgery. PCV may be the operation of choice for the elective treatment of duodenal ulcer; however, it remains undetermined whether the recurrent ulcer rate following PCV will be sufficiently low that the procedure can retain a position of superiority over SV-A-BI.

Diarrhea↗

Physiology of aging: metabolic changes during the climacteric and menopausal periods.

Endocrine regulation is altered with age. Changes in hormone secretory rates, patterns of secretion, and responses to physiologic and pharmacologic stimuli have been demonstrated. Target tissue sensitivity to hormones appears to be age related and to involve hormone receptor mechanisms, enzymatic responses, and carrier proteins. The aging process reflects changes in cellular structure and metabolism that decrease the function and efficiency of tissues. Structural changes occur with age and are characterized by a loss of elastic tissue, accumulation of highly crosslinked collagen, reduction in ground substance, and an increase in a cellular fluorescent pigment called lipofuscin. These changes decrease the pliability of tissues and alter membrane permeability. Modifications in protein synthesis and enzymatic systems may predispose the aged to autoimmune and neoplastic disease. Endocrine diseases are common in the aged and often may be atypical in their presentation. Cancer is common in the elderly and may be associated with endocrine manifestations because the tumor is producing hormones. Physicians must be aware of these syndromes so that a correct diagnosis can be established, treatment instituted, and the quality of life improved. Laboratory test results in the aged must be carefully interpreted because most aged patients are taking medications that interfere with endocrine tests and also the normal range for the elderly has not been clearly established. Abnormal laboratory diagnostic tests are common in the aged and do not always imply endocrine disease. No hormone can reverse the natural process of aging; however, hormones do regulate all metabolic functions and the neuroendocrine system plays a key role in all phases of growth, maturation, and aging.

Adrenal Gland Diseases↗

Relationship of renal hemodynamic and functional changes following intravascular contrast to the renin-angiotensin system and renal prostacyclin in the dog.

Deterioration in renal function has been observed after the use of intravascular contrast media. In an attempt to identify factors responsible for this phenomenon, meglumine iothalamate (Conray 60), in a dosage range of 2.5-3.3 ml/kg, was injected as a bolus into the aorta of dogs. Serial measurements were made of parameters of renal function as well as of changes in aortic and renal venous levels of angiotensin II, renin activity, and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin. The major findings were (1) an initial, brief increase followed by approximately a 20% sustained decrease in renal blood flow and creatinine clearance, (2) no significant changes in angiotensin II and renin levels, and (3) a significant decline in the renal secretory rate of 6-keto-PGF1 alpha. These observations suggest that the suppression of prostacyclin, rather than the activation of the renin-angiotensin system, may contribute to the renal function changes attending the use of intravascular contrast media.

6-Ketoprostaglandin F1 alpha↗

Effect of cholecystokinin-octapeptide on total parenteral nutrition-induced changes in hepatic bile secretion and composition in the rat.

These studies investigated the ability of twice-daily administration of cholecystokinin-octapeptide (CCK-8) to prevent changes in hepatic bile secretory function and bile composition resulting from total parenteral nutrition (TPN) in young, growing rats. Bile was collected from the common duct before and during i.v. infusion of sodium taurocholate following 7 days of TPN. TPN resulted in a reduction of hepatic bile flow, reduced bile molar cholesterol and phospholipid content, and reduction of the taurocholate secretory rate maximum (SRm) and bile salt-independent bile flow (BSIF). Rats treated with CCK-8 throughout their TPN retained high bile flows, BSIF, and SRm. CCK-8 at the dose used did not correct abnormalities in the hepatic bile composition or the magnitude of bile flow generated in response to i.v. taurocholate infusion. These findings suggest that the ability of CCK-8 to maintain high bile flows during TPN may have prophylactic relevance for prevention of TPN-induced gallbladder disease. However, these studies also suggest that a component of current TPN systems induces damage to hepatic bile metabolism and excretion that is additional to that due to the reduced stimulation of bile flow that accompanies elimination of oral food intake.

Animals↗

Secretion of saliva by the rabbit mandibular gland in vitro: the role of anions.

Salivary glands form their secretions by first elaborating an isotonic plasma-like primary fluid in the endpieces and then modifying the composition of this secretion during its passage along the gland duct system. We have studied the role of extracellular anions in both primary secretion and ductal modification with a recently developed technique for isolation and perfusion of the rabbit mandibular gland. Neither of the major extracellular anions (Cl- or HCO-3) is essential for primary fluid secretion. HCO-3 can be removed altogether and replaced with Cl- without diminution in secretory rate, provided that extracellular pH is maintained at 7.4, and its replacement with acetate actually enhances secretion. Complete replacement of Cl- with Br- also enhances secretion and replacement with I-, NO-3, CH3SO-4 or isethionate supports secretion but at progressively diminishing rates. Our data do not yet allow us to distinguish between an electroneutral Na+-Cl- cotransport model or a double countertransport (Na+-H+ plus Cl--HCO-3) model as the basis of primary salivary secretion, or to propose any more suitable alternative model. With respect to ductal modification of the primary saliva, HCO-3 omission inhibits ductal Na+ absorption (i.e. salivary Na+ concentration rises). This inhibition is probably related to an effect of pH on the postulated Na+-H+ exchanges mechanism in the luminal duct membrane since it can also be induced by lowering perfusate pH, and reversed by substitution of perfusate HCO-3 with acetate (which enters saliva) but not HEPES (which does not enter the saliva). Substitution of perfusate Cl- with other anions seems not to inhibit ductal Na+ and K+ transport markedly.

Acetylcholine↗

Growth hormone hyperresponsiveness to growth hormone-releasing hormone in patients with severe liver cirrhosis.

Patients with severe liver disease often have high baseline plasma GH levels and/or paradoxical GH release in response to several secretagogues, e.g. TRH. In this paper, we have investigated in a group of cirrhotic patients the GH response to GH-releasing hormone (GHRH) and evaluated the effectiveness of GHRH to cause GH release in TRH responder and non-responder patients. Ten patients and seven age- and sex-matched control subjects were given bolus injections of GHRH (0.1 and 1.0 microgram/kg i.v. on separate occasions). GHRH 0.1 microgram/kg failed to cause a GH response in both control and cirrhotic subjects, but 1.0 microgram/kg caused a significantly higher GH response in patients than in controls. Evaluation of the GH response curve after GHRH revealed a similar pattern of secretion in the TRH-responders (four subjects) and non-responders (six subjects). These results suggest that the enhanced GH responsiveness to GHRH in cirrhotic patients may contribute to their high baseline GH levels and/or secretory rate, and the mechanism(s) of the paradoxical GH rise after TRH seems to be separate from that for GH hyperresponsiveness to GHRH.

Aged↗

Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus.

OBJECTIVE: To estimate the half-life of growth hormone in young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates. DESIGN: In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous infusion of somatostatin under three different glucose clamp conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l); hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. PATIENTS: Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study. RESULTS: Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data were therefore pooled yielding an overall mean GH half-life of 13.6 minutes (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1 minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and 13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH half-life during the infusions studies did not vary with repeated exposure but was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than during the bolus studies (P less than 0.001). CONCLUSIONS: The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (insulin-dependent) diabetes mellitus.

Adolescent↗

Effect of carbenoxolone on alkaline secretion by isolated amphibian gastric and duodenal mucosa.

The influence of carbenoxolone sodium on HCO-3 transport has been examined in spontaneously alkalinizing amphibian antral (Necturus and Rana catesbeiana) and proximal duodenal (Rana catesbeiana) mucosa and in cimetidine-treated fundic mucosa (Rana temporaria) in vivo. Low concentrations of carbenoxolone (10(-6)-10(-4) mol/l, serosal side and 10(-5) mol/l, luminal side) did not affect the secretory rate or electrical properties of these tissues. In the stomach a higher concentration of carbenoxolone (10(-3) mol/l, serosal side) caused an immediate fall in transmucosal potential difference (PD) and electrical resistance. There was an initial decrease in the rate of HCO-3 transport followed by an increase in titratable alkalinization due to passive permeation of base from the serosal bathing solution. The non-steroidal anti-inflammatory agent ibuprofen (3 x 10(-3) mol/l, serosal side) inhibited alkaline secretion while the bile salt sodium taurocholate (10(-4) mol/l, luminal side) converted net alkaline secretion to a titratable acidity in cimetidine-treated fundus. Pretreatment of the mucosa with carbenoxolone (10(-4) mol/l) did not influence the response to taurocholate but when added with ibuprofen it potentiated the inhibitory effect of this drug on fundic alkaline secretion. In contrast, prostaglandin E2 (10(-6) mol/l) markedly reduced the inhibition of fundic alkaline secretion caused by ibuprofen. The anti-ulcer properties of carbenoxolone do not appear to be related to effects on gastroduodenal HCO-3 transport.

Animals↗

Effects of histamine and histamine antagonists on hepatic bile flow in the conscious sheep.

The effects of histamine and histamine antagonists on bile flow have been studied using the cholecystectomized conscious sheep. Histamine stimulated bile flow in a dose-dependent manner (D50 = 15.7 micrograms/h per kg). Free water and HCO3-output were increased after intravenous histamine infusion. With histamine at 120 mg/h per kg, there was a 41.0 (s.d. = 4.6)% and 38.7 (s.d. = 4.2)% (n = 6) increase in bile volume and HCO3-output respectively. Bile salt concentration was decreased after intravenous histamine, but net bile salt secretory rate remained unchanged. There was no change observed in the molar ratios of bile salts: phospholipids: cholesterol. Total lipids were decreased from 2.2 (s.d. = 0.3) to 1.60 (s.d. = 0.4) g/dl (n = 6). The corrected lithogenic index did not change significantly. 14C-Erythritol clearance also increased during histamine infusion in a dose-dependent manner but did not correspond to increments in bile flow. The histamine H1-receptor antagonist, diphenhydramine 0.05-1.0 mg/h per kg did not alter histamine stimulated bile flow. The H2-receptor antagonists, cimetidine (0.5-4 mg/h per kg) and ranitidine (0.05-0.5 mg/h per kg) progressively reversed the histamine-induced choleresis. Maximum inhibitory effect was attained at 2.0 and 0.25 mg/h per kg for cimetidine and ranitidine, respectively. At these levels, variation of intravenous infusion of histamine did not result in competitive displacement of the inhibitory response by either cimetidine or ranitidine. Moreover, concomitant infusion of diphenhydramine at 1.0 mg/h per kg potentiated the inhibitory effect of cimetidine or ranitidine on histamine-induced choleresis. Histamine increases the bile salt independent component of hepatic bile flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The chromogranins and the counter-regulatory hormones: do they make homeostatic sense?

1. The chromogranins are ubiquitous proteins which are co-stored and co-secreted with many peptide hormones. All appear to be powerful inhibitors of endocrine secretions. This poses a problem. 2. When endocrine glands are involved in the efferent limbs of homeostatic loops, they are message transmitters. The self-inhibition caused by the co-secretion of a chromogranin will, on the face of it, erase the message. 3. Pairs of counter-regulatory homeostatic hormones also present a problem. 4. If both members of the pair have clearly defined set points, as suggested by their 'time integral' (or 'growth with time') responsiveness to deviations from set point, then, if the two set points are not exactly the same, one or other member will always register an error, leading, eventually, to an overwhelmingly large and unnecessary response. 5. Our model eliminates both paradoxes, and emphasizes the importance of counter-regulation and the co-secretion of chromogranins in 'zero steady-state error' (ZSSE) homeostasis. 6. If hormone A is secreted into the blood in progressively increasing amounts when [Q], the plasma concentration of substance Q, is low, and in decreasing amounts when [Q] is high; and hormone B responds in the opposite manner, then there will be a [Q], designated [Q]p, at which the secretory rate increase, or decrease, of the two hormones is exactly the same. 7. If, in addition, the secretion of both hormones is stimulated by low plasma chromogranin levels, [Cg], but inhibited by high [Cg] then there will be a different [Q]p for every chromogranin concentration in the blood. 8. At one of these points (at a unique [Q] and [Cg]) the concentration of neither hormone will increase or decrease. This is the equilibrium point to which, according to our model, the system always returns regardless of disturbances within physiological limits. 9. This is robust ZSSE control.

Animals↗

Enhancement of pentagastrin-induced gastric acid secretion by clonidine in the conscious dog.

The effect of intravenous clonidine on pentagastrin-induced gastric acid secretion has been studied in conscious dogs with Heidenhain pouches. Dose-dependent enhancement of secretion was found in response to clonidine (5-20 mu/kg). Clonidine (20 mug/kg) increased the maximal secretory rate to pentagastrin to a value not significantly different from the maximal response to histamine.

Animals↗

Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus.

1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

Adrenal Cortex↗