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PubMed2005

Adiposity in middle-aged women is associated with genetic taste blindness to 6-n-propylthiouracil.

OBJECTIVE: Taste blindness to the bitterness of 6-n-propylthiouracil (PROP) may be a genetic marker for food preferences and dietary choices that ultimately influence body weight. A previous study in middle-aged women showed that those who were taste blind to PROP (i.e., nontasters) had higher BMIs than those with the greatest sensitivity to PROP (i.e., supertasters). This study tested the hypothesis that the nontaster phenotype was associated with greater adiposity in middle-aged women. RESEARCH METHODS AND PROCEDURES: Forty women with a mean BMI of 26.6+/-1.3 kg/m2 and a mean age of 41.8+/-1.8 years were recruited from the local community. They were classified as nontasters (n=8), medium tasters (n=18), or supertasters (n=14) of PROP using a filter paper screening procedure. Anthropometric measures included height, weight, body fatness, triceps skinfold thickness, and waist circumference. Dietary restraint and disinhibition were also measured to assess cognitions associated with body weight. RESULTS: BMI was 6.2 units higher in nontaster women compared with supertaster women (29.7+/-0.9 vs. 23.5+/-0.9, respectively; p<0.05). Body fatness (p<0.01) and triceps skinfold thickness (p<0.05) were also higher in these women. Waist circumference showed a trend in the appropriate direction. Although disinhibition was associated with greater adiposity, the relation between PROP status and adiposity was not altered after controlling for disinhibition. DISCUSSION: The PROP nontaster phenotype was strongly associated with several measures of adiposity in middle-aged women. These data confirm our previous findings and suggest that the PROP polymorphism may be a reliable indicator of weight gain susceptibility.

Adipose Tissue↗
PubMed1999

Effects of oral propylthiouracil treatment on nitric oxide production in rat aorta.

The effects of oral propylthiouracil (PTU) treatment on vascular nitric oxide (NO) production were studied in the rat aorta. Rats were fed a standard low fat diet with or without 0.1% PTU, for 2 or 4 weeks, or for 2 weeks with additional thyroxine injections. Concentration response curves were then constructed to phenylephrine (PE) in both endothelium-intact and denuded aortic rings from these animals and after incubation with 0.1 mM L-N(G)nitroarginine (L-NOARG). In addition, expression of nitric oxide synthase (NOS) was analysed in sections of aorta from PTU-treated and control rats using rabbit polyclonal antibodies to both inducible NOS (iNOS) and endothelial NOS (eNOS). Oral PTU treatment resulted in a significant reduction in both the maximum response (control, 0.53+/-0.02; 2 week PTU, 0.20+/-0.07; 4 week PTU, 0.07+/-0.02 g mg(-1)) and vessel sensitivity (EC50 values: control, 9.10x10(-8)+/-0.67; 2 week PTU, 7.45x10(-7)+/-1.15; 4 week PTU, 9.73x10(-7)+/-0.45 M) to PE in endothelium-intact vessel rings, as compared to controls (P<0.05). Both endothelial removal and incubation with L-NOARG restored the maximum response after 2, but not 4 weeks, although, in general, vessel sensitivity was not altered by either treatment. Vessels from PTU-treated rats given thyroxine injections showed no significant differences between any of the dose response curve parameters. Immunohistochemical analysis suggested that labelling for eNOS may be increased after PTU treatment as compared to control animals, whereas iNOS antibody immunoreactivity was not different between the two groups. These results suggest that the hyporesponsiveness to PE observed after oral PTU treatment is, in part, due to enhanced nitric oxide (NO) production by the endothelium, and demonstrate for the first time that thyroid hormones may play a role in the regulation of eNOS activity in the rat aorta.

Animals↗
PubMed2000

Direct effects of propylthiouracil on testosterone secretion in rat testicular interstitial cells.

The aim of this study was to investigate the mechanism by which propylthiouracil (PTU) exerts its inhibitory effects on the production of testosterone by rat testicular interstitial cells. The plasma testosterone concentration was decreased 60 and 120 min after an intravenous infusion of PTU (10 or 20 mg kg(-1)), but the concentration of plasma T(4) was unaffected by the drug treatment. Exposure of anterior pituitary tissue to PTU (3-12 mM) in vitro did not affect either basal or gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. PTU (3 - 12 mM) inhibited both the basal and the human chorionic gonadotropin (hCG, 0.05 i.u. ml(-1))-stimulated release of testosterone from rat testicular tissue in vitro; at the highest concentration tested (12 mM), it also inhibited the forskolin or 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cyclic AMP)-stimulated release of testosterone. The 25-OH-cholesterol (10(-7)-10(-5) M)-stimulated release of pregnenolone and testosterone by the testicular interstitial cells was inhibited by PTU (12 mM, P<0.05). The results suggest that the inhibitory actions of PTU on testosterone secretion are exerted, at least in part, at the testicular level through a mechanism which is independent of thyroid status and which involves a reduction in P450scc activity and, hence, in the conversion of cholesterol to pregnenolone.

Animals↗
PubMed2003

Direct effect of propylthiouracil on progesterone release in rat granulosa cells.

1. The present study was to investigate the direct effect and action mechanism of propylthiouracil (PTU), an antithyroid drug, on the production of progesterone in rat granulosa cells. 2. PTU (3-12 mM) decreased the basal and human chorionic gonadotropin (hCG)-stimulated release of progesterone from rat granulosa cells. 3. PTU (3-12 mM) attenuated the stimulatory effects of forskolin and 8-bromo-cyclic 3':5'-adenosine monophosphate on progesterone release from rat granulosa cells. 4. PTU (12 mM) inhibited the activities of both the cytochrome P450 side-chain cleavage enzyme (P450scc, conversion of 25-hydroxyl cholesterol to pregnenolone) and the 3beta-hydroxysteroid dehydrogenase (conversion of pregnenolone to progesterone) in rat granulosa cells. PTU decreased the V(max) but increased the K(m) of P450scc. 5. PTU (12 mM) decreased the hCG-increased amount of steroidogenic acute regulatory (StAR) protein in rat granulosa cells. 6. The present results suggest that PTU decreases the progesterone release by granulosa cells via a thyroid-independent mechanism involving the inhibition of post-cAMP pathway, and the activities of intracellular calcium, steroidogenic enzyme, and StAR protein functions.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Kinetic determination of carbimazole, methimazole and propylthiouracil in pharmaceuticals, animal feed and animal livers.

Kinetic methods are proposed for the determination of carbimazole(CBZ), methimazole(MMI) and propylthiouracil(PTU) based on their inhibitory effects on the palladium(II)-catalysed reaction between the pyronine G and hypophosphite ions. The reactions are monitored spectrophotometrically at 548 nm. The influence of reaction variables and the interfering effect of other substances were studied. Under the selected experimental conditions (CBZ: 3.6 x 10(-5) mol l-1 pyronine G; pH 3.0; 0.7 microgram ml-1 PdII and 0.2 mol l-1 H2PO2-; MMI: 6 x 10(-5) mol l-1 pyronine G, pH 3.0; 0.7 microgram ml-1 PdII, 0.4 mol l-1 H2PO2-; PTU: 3.6 x 10(-5) mol l-1 pyronine G; pH 3.0; 0.7 microgram ml-1 PdII and 0.3 mol l-1 H2PO2-), these three antithyroids were determined in the following ranges: CBZ, 0.04-0.70 microgram ml-1; MMI, 0.04-0.50 microgram ml-1; PTU 0.08-1.00 microgram ml-1. The methods were applied to the determination of CBZ, MMI and PTU, in pharmaceuticals, animal feed and animal livers.

Animal Feed↗
PubMed2001

Effect of propylthiouracil on adenosine deaminase activity and thyroid function in patients with psoriasis.

BACKGROUND: T-cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T-cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system. OBJECTIVES: To investigate whether ADA activity may be related to psoriasis and whether oral PTU affects ADA activity and gives clinical improvement in psoriatic patients. METHODS: ADA activities were measured in plasma, erythrocyte and tissue samples of patients with psoriasis before and after 2 months of treatment with either PTU 100 mg three times daily or PTU plus thyroxine 25 microg once daily (to prevent possible hypothyroidism, which may be induced by PTU) as well as in healthy controls. The severity of the disease was evaluated before and after treatment according to Psoriasis Area and Severity Index (PASI) scores. Routine analyses and thyroid function tests were also carried out during the study. RESULTS: All patients showed significant clinical improvement in their lesions and decreased PASI scores after the treatments. Elevated baseline ADA activities in skin and plasma were found to be lower, and decreased baseline erythrocyte ADA was higher, after the treatments in all patients, and they were not different from control values. Although thyroid function tests were not affected by the treatments, serum thyroid-stimulating hormone levels were found to be higher after the treatments, and there was a larger increase in patients treated with PTU alone. However, none of the patients had clinical hypothyroidism or cytopenia. CONCLUSIONS: ADA activity may be clinically useful for indicating T-cell activation in psoriasis. Because of its antiproliferative and immunomodulatory effects, antioxidant potential and low toxicity, PTU may be an effective agent in the treatment of psoriasis.

Adenosine Deaminase↗
PubMed2001

Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism.

OBJECTIVE: Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease. SUBJECTS: Seventy-one patients with newly diagnosed Graves' disease were studied. METHODS AND MEASUREMENTS: Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group. CONCLUSIONS: During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.

Adult↗
PubMed2001

Frequency of appearance of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO-ANCA and clinical manifestations.

OBJECTIVE: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO-ANCA in these cases was suspected of being related to PTU because the titres of MPO-ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO-ANCA and vasculitis during PTU therapy, or on the incidence of MPO-ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease. PATIENTS: We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO-ANCA, and for the development vasculitis after starting PTU therapy. Twenty-nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23.6 months (range: 3-37 months). MEASUREMENTS: MPO-ANCA was measured at intervals of 2-6 months. RESULTS: Before treatment, the MPO-ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U/ml). Three (4.1%) of the 73 patients were positive for MPO-ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO-ANCA titres transiently increased to 12.8 and 15.0 U/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO-ANCA titre increased to 204 U/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO-ANCA titre decreased to 20.7 U/ml by 4 months after discontinuing PTU. CONCLUSIONS: PTU therapy may be related to the appearance of MPO-ANCA, but MPO-ANCA does not appear to be closely related to vasculitis.

Adolescent↗
PubMed2003

Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole.

H2O2 generation is a limiting step in thyroid hormone biosynthesis. Biochemical studies have confirmed that H2O2 is generated by a thyroid Ca2+/NADPH-dependent oxidase. Decreased H2O2 availability may be another mechanism of inhibition of thyroperoxidase activity produced by thioureylene compounds, as propylthiouracil (PTU) and methimazole (MMI) are antioxidant agents. Therefore, we analyzed whether PTU or MMI could scavenge H2O2 or inhibit thyroid NADPH oxidase activity in vitro. Our results show that PTU and thiourea did not significantly scavenge H2O2. However, MMI significantly scavenged H2O2 at high concentrations. Only MMI was able to decrease the amount of H2O2 generated by the glucose-glucose oxidase system. On the other hand, both PTU and MMI were able to partially inhibit thyroid NADPH oxidase activity in vitro. As PTU did not scavenge H2O2 under the conditions used here, we presume that this drug may directly inhibit thyroid NADPH oxidase. Also, at the concentration necessary to inhibit NADPH oxidase activity, MMI did not scavenge H2O2, also suggesting a direct effect of MMI on thyroid NADPH oxidase. In conclusion, this study shows that MMI, but not PTU, is able to scavenge H2O2 in the micromolar range and that both PTU and MMI can impair thyroid H2O2 generation in addition to their potent thyroperoxidase inhibitory effects.

Antithyroid Agents↗
PubMed2003

Antineutrophil cytoplasmic antibody positive alveolar haemorrhage during propylthiouracil therapy for hyperthyroidism.

Recently, propylthiouracil (PTU) has been thought to be one of the possible causes of antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis syndrome, resulting in glomerulonephritis and, infrequently, diffuse alveolar haemorrhage (DAH). The mechanism of ANCA-positive vasculitis during PTU therapy is still unknown. Herein, we describe the case of a 59-year-old woman who developed myeloperoxidase (MPO)- and proteinase 3 (PR3)-ANCA positive DAH, without any other organ system involvement, during PTU therapy. Diminution and discontinuation of PTU resulted in a positive response. To our knowledge, this is the first documentation of both MPO- and PR3-ANCA-positive DAH, without systemic manifestations, developing during PTU therapy.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Type II and type III monodeiodinase activities in the skin of untreated and propylthiouracil-treated cashmere goats.

The presence or absence of types I, II and III iodothyronine monodeiodinase enzymes (MDI, MDII and MDIII) and their levels of activity in the skin of goats, which were orally dosed for 60 days with 0, 1.1, 2.2, 4.4, 8.8, 17.5, or 35 mg(-1)kg liveweight day(-1)of the anti-thyroid, enzyme-inhibiting drug, propylthiouracil (PTU), were determined. Contrary to our earlier report that PTU did not influence skin MDII activity, the currect more thorough investigation (in terms of numbers of observations and the efficiency of the enzyme extraction procedure) indicated that doses of 1.1.to 17.5 mg kg(-1)liveweight induced a 2 to 3 fold increase (P = 0.01) in MDII activity. However, in three of the four goats treated with 35 mg kg(-1)group, activity was similar to that of control animals. There were no significant differences between treatments in MDIII activity but there was a trend towards lower levels of activity in the goats dosed with 17.5 and 35 mg kg(-1). It is concluded that there is significant MDII and MDIII activity in the skin of goats and that although there is none of the PTU -sensitive MDI enzyme, synthesis of T3 within the skin could nevertheless be modified through increases in MDII activity induced by lower T4 concentrations in the circulation caused by PTU. Changes in pattern of fibre moult induced by treatment with low doses of MD-inhibiting drugs may therefore be achieved through this effect. Since MDII and MDIII enzyme activity may be reduced by high doses of PTU, prolonged treatment with high doses of PTU may have adverse effects on skin tissue.

Animals↗
PubMed1979

Effects of propylthiouracil and methylmercaptoimidazol on metabolism of thyroid hormones by cultured monkey hepatocarcinoma cells.

Monkey hepatocarcinoma cell monolayer cultures (NCLP-6E) metabolized thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine and 3,3'-diiodothyronine by phenolic and nonphenolic ring deiodinations and sulfation of the deiodinated products, as shown in previous work with this system. The effects of the antithyroid drugs, propylthiouracil (PTU) and methylmercaptoimidazole (MMI), on these processes was investigated. PTU, at 0.1 and 1 mM, inhibited only phenolic ring deiodination. MMI at 1 mM had no effect, but 32 mM inhibited deiodination of both rings as well as sulfation. The findings suggest that the increased serum rT3 level caused by PTU in vivo is the result of decreased rT3 deiodination, in contrast to the increased rT3 production which is caused by starvation.

Animals↗
PubMed1983

Effects of propylthiouracil, methimazole and thyroidectomy on liver and plasma proteins: differential response to thyroxine.

Differential effects of propylthiouracil (PTU), methimazole (MMI) and thyroidectomy (Tx) on liver and plasma proteins have been studied in rats, some of which have been simultaneously treated with L-thyroxine (T4). Although the absolute liver weights were lower in all hypothyroid groups, the relative liver weights (g/100 g) were significantly higher in PTU and MMI groups, while in Tx group they were lower. T4 administration raised the absolute liver weights in all groups, even though there was no significant difference between relative weights in PTU and MMI groups. In Tx group, however, the relative weight was restored to control level. One of the constituents responsible for the increased relative liver weight was liver protein. The increased liver protein concentration (mg/g) was, however, not reflected in the synthesis rate which was uniformly low in all groups inspite of T4 therapy. Plasma albumin concentration was raised in hypothyroid rats which did not respond to T4 therapy. On the other hand, increased total plasma protein level was restored to normal. Relative 14C-glycine incorporation into albumin, fibrinogen, seromucoids and total proteins was reduced from 14 to 30%, 5.2 to 19% and 13 to 23% of control in PTU, MMI and Tx groups, respectively. Of these, only MMI and Tx groups appeared to be responsive to T4 therapy. Of all the protein fractions, fibrinogen synthesis was least affected by various treatments. To some extent these observations may be explained on the basis of altered general endocrine status and specific extra-thyroidal effects, rather than on the basis of thyroid status alone.

Animals↗
PubMed1983

Differential effects of propylthiouracil, methimazole and thyroidectomy on liver ferritin.

Different groups of rats were made hypothyroid by thyroidectomy (Tx) or treatment with propylthiouracil (PTU) or methimazole (MMI). Some of the hypothyroid rats from each group were simultaneously treated with thyroxine (T4). Liver ferritin concentration and 14C-glycine incorporation into liver ferritin in these rats were studied. Only in MMI-treated rats the ferritin concentration was elevated, which was reduced by simultaneous T4 treatment. PTU treatment resulted in 36-42% reduction in ferritin synthesis, which was not responsive to T4. Thyroidectomy induced 23% enhancement in ferritin synthesis, which was normal in T4-treated Tx rats. The possible causes for these differential effects in hypothyroid rats have been discussed.

Animals↗
PubMed1992

Immediate and dose-response related increase of biliary excretion of reverse triiodothyronine after propylthiouracil administration.

In a group of rats infused with L-thyroxine (0.13 micrograms T4 in 0.6 ml alkaline saline per hour) for 6 h to which an infusion of propylthiouracil (PTU) was added beginning from the 3rd hour (2 mg PTU in 0.6 ml saline per hour) a significant increase of biliary excretion of reverse triiodothyronine (rT3) was found. In another experiment a dose-response related rT3 excretion by bile was observed in groups of rats infused with 0.05, 0.10, 0.20 or 0.40 mg PTU in 1.2 ml alkaline saline per 2 h, all animals receiving a pulse dose of 1 micrograms rT3 at the beginning of PTU infusion. It was concluded that the increase of rT3 excretion results from the inhibition of 5'-deiodinase type I activity in the liver caused by PTU. It thus appears that such phenomenon may be used as in vivo marker of that enzyme activity.

Animals↗
PubMed1993

Effects of thyroxine supplement on serum insulin-like growth factor-binding activity in propylthiouracil induced hypothyroid cockerels.

In propylthiouracil (PTU)-fed (g/kg feed) hypothyroid cockerels, serum levels of growth hormone (GH), but not insulin-like growth factor (IGF)-1, tended to rise and those of IGF-binding activity to fall. Thyroxine (T4) supplement (200 micrograms/kg/day) to PTU-fed cockerels for 8 days produced a hyperthyroid state and reversed these serum parameters. A chromatographic analysis of serum proteins revealed that T4 supplement markedly enhanced the IGF-binding activity of a 30 kDa protein and slightly lowered that of a 150 kDa protein, suggesting that T4 increases unsaturated IGF-binding proteins by reducing circulating IGF-1 concentrations.

Animals↗
PubMed1989

Effects of L-thyroxine and L-triiodothyronine on protein and nucleic acid contents of liver of 6N-2-propylthiouracil treated hypothyroid singi fish, Heteropneustes fossilis bloch.

Three consecutive injections of 12.5 X 10(-10) and 25 X 10(-10) moles/g of L-thyroxine (T4) or a single injection of L-triiodothyronine (T3) at 7.5 X 10(-10) moles/g to Singi fish caused an increase in liver protein and RNA contents, whereas similar injections of 50 X 10(-10) moles/g of T4 or 75 X 10(-10) moles/g of T3 caused a fall in these cellular constituents in liver. Treatments of Singi fish with thiourea (1 mg/ml) for 30 days caused a fall in the protein and RNA contents in liver which were restored to the euthyroid control level by a single injection of 7.5 X 10(-10) moles/g of T3 or three consecutive injections of T4 at 12.5 X 10(-10) moles/g dose. Administration of T4 (12.5 X 10(-10) moles/g, three consecutive injections) along with 6N-2-propylthiouracil (PTU) at 20 micrograms/g of b. w. in six consecutive injections to the thiourea treated (hypothyroid) fish failed to cause any change in hepatic protein and RNA contents in comparison to only PTU-treated hypothyroid fish, but a single injection of 7.5 X 10(-10) moles/g of T3 to the PTU-treated hypothyroid fish increased these cellular constituents of liver. A dose-dependent biphasic nature of thyroid hormone action, a higher potency of T3 than T4 and the probable 'prohormone' nature of T4 have been documented in case of Singi fish in the present experiments.

Animals↗
PubMed1985

Response of the hypothalamo-neurohypophyseal axis (AVP system) and the kidney to salt load in young propylthiouracil-treated rats.

The development of the ability of the kidney to concentrate urine was studied in normal and propylthiouracil-treated rats by measuring urinary sodium concentration and osmolarity at different ages. It was shown that the normal animals, but not the PTU-treated ones were able to concentrate urine at 35 days of age. The response of the hypothalamo-neurohypophyseal axis (AVP system) and that of the kidney were investigated in the two categories of animals at 35 days of age by measuring concomitantly the AVP content of the hypothalamus and neurohypophysis, the AVP plasma concentration and the natremia and plasma osmolarity at various intervals after intraperitoneal injection of a 5% NaCl solution. In normal, as well as in PTU-treated rats, salt load did not lead to significant modifications of the hypothalamic AVP content. In comparison with normal rats, the neurohypophysis of the PTU-treated ones released AVP more slowly, but with a similar amplitude. In normal rats, the plasma AVP concentration was already maximal 30 min after salt load and then decreased and returned to the normal value at 2 hrs; at the same time, the natremia and plasma osmolarity also recovered their normal value. In contrast, the plasma AVP concentration as well as the natremia remained high 1 h 30 after salt load in PTU-treated rats. It is concluded that PTU-treated young rat is unable to compensate the salt load in normal delays. Beside the slowing in AVP release by neurohypophysis and decreased AVP plasma level, the responsiveness of the kidney seems to be altered.

Aging↗