Mechanisms of action of p-chlorophenylalanine in stimulating sexual receptivity in the female rat.
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Biomedical subjects
Publications and source records attributed to C A Wilson.
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White weanling rats were given intragastrically 4 doses of T-2 toxin (3 alpha-hydroxy-4 beta-1,5-diacetoxy-8 alpha-(3-methylbutyryloxy)-12,13-epoxytrichothec-9-ene) a secondary metabolite of certain Fusarium species, 6 out of 9 treated rats developed increased blood pressure; these animals showed microscopically severe cardiovascular abnormalities. Occasional contamination of foodstuffs wh Fusarium may contribute to hypertension and cardiovascular lesions in animals and man.
Features of the reproductive axis in the genetically hypogonadal, obese mouse (genotype, ob/ob) were examined at 5-8 months of age and compared with those of wild-type litter mates. Hypothalamic concentrations of dopamine and 5-hydroxytryptamine were normal. Those of 5-hydroxyindoleacetic acid, noradrenaline and LH-RH were raised. LH-RH was biologically active. Pituitary concentration of LH was normal, but that of FSH was raised. Serum concentrations of LH and FSH, compared with those of wild-type animals, were normal and low, respectively. Gonad and accessory sex organs weights were reduced. These findings suggest that the release of FSH but not LH is defective in the ob/ob mouse. Preliminary in-vitro experiments indicated that the pituitary gland responded normally or even supernormally towards LH-RH in its release of LH. The defect in the reproductive axis of the obese mouse may be due to inadequate release of LH-RH although an insensitivity of the pituitary gland towards LH-RH in its release of FSH cannot be excluded.
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1. Blood pressure and heart rate responses to head-up tilt, standing, the Valsalva manoeuvre, sustained handgrip and cutaneous cold were measured in 27 haemodialysis patients (10 of whom had episodes of haemodialysis-induced hypotension) and 15 control subjects to assess autonomic nervous function. Plasma noradrenaline levels were measured at rest and during head-up tilt. 2. Mean resting supine blood pressure, heart rate and plasma noradrenaline levels were higher in haemodialysis patients than in the control subjects. There was no fall in blood pressure during head-up tilt or standing. The ratio of the R--R intervals of the thirtieth and the fifteenth heart beat after standing (30:15) was lower in the patients; this may be related to their higher resting heart rate. Head-up tilt raised plasma noradrenaline levels in both groups. Heart rate responses to the Valsalva manoeuvre were similar in the patients and control subjects. 3. Systolic blood pressure and heart rate responses to sustained handgrip were similar in both groups. Diastolic and mean blood pressure changes, however, were lower in the patients. The blood pressure and heart rate responses to cutaneous cold were similar in the patients and control subjects. 4. We conclude that generalized autonomic nervous dysfunction does not appear to cause haemodialysis-induced hypotension in patients with chronic renal failure on maintenance haemodialysis.
The light-emitting reaction of firefly luciferin and luciferase is a common ingredient in the quantification of adenosine triphosphate (ATP) extracted from the microbiota of environmental samples. Both portions of the light-emission phase of the luciferase reaction, the primary flash within 3 s of mixing and the secondary decay in the luminescence following the flash, have been used to quantify extracted ATP. However, the magnitude of the secondary phase is influenced by nucleotides other than ATP. The impact of this influence on the quantification of ATP was studied in samples collected from the water covering a salt marsh. Analysis by integration of the secondary decay portion of the emission yielded values of ATP per cubic metre that were consistently higher than those obtained by peak height analysis of the same extracts. Assays using the integration technology resulted in values that were up to 8 (mean = 3.6) times higher than corresponding values determined by peak height analysis in unfractionated samples (total microbial biomass) and up to 16 (mean = 4.8) times higher in water that had been prefiltered with a 1.0 micrometer filter (bacterial biomass).
Plasma concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH) were measured by radioimmunoassay at various times during the oestrous cycle of the rat. Variations in plasma alpha-MSH concentrations occurred throughout the oestrous cycle. Plasma alpha-MSH concentrations were low during the day of dioestrus 1 and rose during the evening reaching peak levels at around 02.00 and 06.00 h on dioestrus 2. Plasma alpha-MSH concentrations then fell and remained low throughout the rest of dioestrus 2. A different pattern was observed during pro-oestrus and oestrus. On those days peak alpha-MSH concentrations occurred during the morning and persisted until the onset of the dark period at around 17.00 h. Plasma alpha-MSH concentrations in ovariectomized rats were found to be increased 24 h after administration of a single injection of oestradiol benzoate and at 12 and 36 h after a single injection of progesterone. It is suggested that these ovarian steroids may influence the rhythm in plasma alpha-MSH concentration that occurs during the oestrous cycle.
Measurements of the refractory period of stria terminalis neurones that are sensitive to testosterone propionate, of sexual behaviour and of plasma levels of LH were taken in castrated rats at various times after initiation of treatment with testosterone propionate. Levels of LH dropped within 24 h, before there was any change in neuronal refractory periods. The period of latency to mounting, however, was reduced to its shortest only after 7-8 days and ejaculations first occurred at the same time; these sexual responses correlated in time with reduction of the neuronal refractory period to its lowest level.
The effect of indapamide on the peripheral circulation was investigated in hypertensive patients using a xenon washout technique. Resting muscle blood flow increased by 38% after 1 week's treatment in 5 patients and by 52.6% after 6 weeks treatment in 4 patients. Exercise muscle blood flow increased by 18% in 4 patients after 6 weeks' treatment. Resting supine and standing blood pressure was decreased by indapamide after 2, 4 and 6 weeks of treatment. Exercise systolic blood pressure was not changed by indapamide. The results in this pilot study suggest that peripheral resistance is reduced by a direct action on the vessel wall.
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Immature rats can be induced to ovulate with pregnant mare serum (PMS) as long as they weigh over 60 g. In the rats weighing less than 60 g 5-hydroxytryptamine (5HT)-60 micrograms/rat intraventricularly or 2 micrograms/rat in the paraventricular nucleus (PVN)-stimulated ovulation. Injections into several other hypothalamic nuclei were ineffective. In rats weighing greater than 60 g, lesions of the PVN or injection of 10 micrograms/rat p-chlorophenylalanine into the PVN inhibited ovulation. The hypothalamic levels of 5HT and 5-hydroxy indole acetic acid (5HIAA) were generally lower in the afternoon and evening in the less than 60 g when compared with the greater than 60 g rats. It is possible that increased 5HT activity is required to stimulate ovulation and that its site of action is the PVN.
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RMI 12,936 inhibited the vaginal cycle and ovulation in the rat. This effect was not mimicked by oestrogen and was partly reversed by progesterone. Ovulation was restored by injection of hCG and the inhibition was associated with reduced cyclic and tonic LH secretion while hypophysial LH levels were generally unaffected. Hypophysial sensitivity to LH-RH was reduced compared with that when ovulation was blocked with sodium pentobarbitone. It is concluded that RMI 12,936 blocks ovulation by causing a reduction in hypophysial sensitivity to LH-RH and that this is probably an antiprogestational effect.