THE PRESENT STATUS OF THE AUTOREGULATION THEORY OF THE PATHOGENESIS OF HYPERTENSION

1. The autoregulation theory of hypertension has been attractive because it postulates a mechanism whereby an early rise in cardiac output becomes ‘transformed’ through normal autoregulatory processes into an elevated total peripheral resistance. 2. ‘Normal’ autoregulation involved in control of blood flow of regional beds is a rapid process compared with the slow changes postulated by the autoregulation theory. 3. Evidence is presented that under appropriate experimental conditions ‘volume’ factors (cardiac output) and ‘constrictor’ factors exert independent long-term effects in developing and in established hypertension. There is little evidence to support the autoregulation theory of hypertension.     

Hyper- and hyposensitivity of central serotonin receptors: [H]serotonin binding and functional studies in the rat

The effect of repeated treatment withd-fenfluramine, a serotonin releaser, or methergoline, a serotonin antagonist, on [³H]5-HT binding was studied in various rat brain areas. In animals with the same pretreatments, the anorectic activity ofm-chlorophenylpiperazine, a serotonin agonist, was investigated.A 14-day treatment withd-fenfluramine caused a significant decrease in the number of [³H]5-HT binding sites (B_max) in the diencephalon. A reduction of binding sites was found in the cortex too whend-fenfluramine was administered for 28 days. Methergoline caused no changes of [³H]5-HT binding in any brain area exmined when given for 14 days but 28-day treatment led to a significant increase in the striatum, hippocampus and cortex.d-Fenfluramine and methergoline caused, respectively, a decrease and increase in the effect ofm-chlorophenylpiperazine on food intake.The data show that central 5-HT receptor numbers and sensitivity may change after repeated treatments with drugs acting on brain serotonin.     

Study on toxicity of butylated hydroxyanisole (BHA) in pregnant gilts and their foetuses

An embryotoxicity study on butylated hydroxyanisole (BHA) was carried out in SPF pigs (Danish Landrace). BHA was incorporated in the diet and administered to pigs in doses of 0, 50, 200 and 400 mg/kg body wt/day from mating (artificial insemination) to day 110 of the gestation period, when the foetuses were removed. Significant lower weight gain was observed in the dams dosed 400 mg/kg body wt/day. Absolute and relative organ weight for the liver and thyroid gland showed a dose-related increase. BHA neither affected the reproduction data nor the incidence of defects in the foetuses.     

INFANT FEEDING, SOMATIC GROWTH AND OBESITY

The calorie concentration and composition of formula may affect the physical growth of the infant. Obesity in childhood has several causes and in many, the onset is in early infancy.     

FLUORIDE, MINERALISATION DEFECTS OF THE ENAMEL, AND TOOTH WIDTH

Abstract. Grahnén, H., Lysell, L., Myrberg, N. and Ollinen, P. (Departments of Pedodontics and Orthodontics, University of Umeå, Sweden and Department of Orthodontics, University of Amsterdam, The Netherlands). Fluoride, Mineralisation defects of the enamel, and tooth width. Acta Paediat Scand, 63: 188, 1974.–The purpose of the investigation was to appraise the frequency of enamel mineralisation defects in 151 children, aged 8–11 years, born and raised in a district in Vasterbotten county in northern Sweden, where the fluoride content of the drinking water ranges up to 2 mg/l, and to examine the mesiodistal widths of the teeth for effects of fluoride in these concentrations. The control group consisted of 213 children who had always lived in a town where the fluoride content of the drinking water was ≫0.0 mg/l. The mineralisation defects were recorded clinically and photographically. Owing to the various ages of the children, only mineralisation defects in permanent incisors and six-year molars were noted. The mesio-distal widths of the teeth were measured on plaster casts. The frequency of enamel fluorosis was high (34%) in those children whose drinking water had a fluoride content of 1.0–2.0 mg/l and also high (31%) in those children living in areas with a fluoride content of 1.0–1.2 mg/l. No satisfactory explanation can be offered for the relatively high frequency of fluorosis. There are, however, variations in the natural fluoride concentration of the ground water and probably also considerable individual variation in water consumption. This stresses the necessity of further investigation of children's fluoride intake. No significant differences in mesio-distal widths of individual teeth could be demonstrated.     

Hypothalamic hyperphagia without plateau in ground squirrels

Hypothalamic lesions infringing on the ventromedial nuclei in thirteen-lined ground squirrels, Citellus tridecemlineatus, were followed by weight gains, despite the fact that the animals were in a weight-loss phase of their annual cycle. Lesioning through chronically implanted electrodes and sham operations showed that the results did not depend on non-specific effects of the surgery. There was no plateau after the lesion-induced weight gain: instead weight loss and continuation of cyclic changes in body weight resumed. The results suggest that a balance between medial and lateral hypothalamic systems is still functional during annual cycles of body weight in ground squirrels.     

Reduction of heroin intake in baboons by an economic constraint

Baboons earned their total food ration in a situation where they were periodically given an opportunity to choose between food and an intravenous infusion of heroin. As the number of daily choices was restricted, food intake remained relatively constant, while heroin intake decreased dramatically.     

Plasma concentration of diazepam and N-desmethyldiazepam in children after a single rectal or intramuscular dose of diazepam

Summary The absorption of diazepam and N-desmethyldiazepam after administration of diazepam solution for parenteral injection per rectum and intramuscularly was studied in 9 children (ages 3–12 years). Rectal administration of diazepam 1 mg/kg led to rapid absorption with plasma levels of 270–320 ng/ml within 5 min, and peak levels of 600–1300 ng/ml 10–60 min after administration. The absorption was comparable to that after intramuscular administration. A second peak in plasma diazepam concentration 6–12 h after dosing was observed in 6 children, which may have been due to mobilization of diazepam from the gastrointestinal mucosa produced by feeding 4 h after administration of the drug. A slowly increasing plasma level of N-desmethyldiazepam was observed during the first 24 h after administration of diazepam.     

Meal pattern of hypophysectomized rats

The daily meal pattern of hypophysectomized rats was studied in order to investigate the possible role of hypophyseal hormones in the control of food intake. A 5-day recording of the ad lib feeding pattern in 10 hypophysectomized rats, compared to controls, confirmed earlier findings of a 50% reduction of the daily food intake. However the observation of maintained diurnal feeding cycle and of a prolongation of day-time meal-to-meal intervals suggests that the lack of hypophyseal hormones does not affect the basic feeding mechanisms. Particularly, no indication exists that the lack of growth hormone disrupts the day-time lipolysis and associated low food intake.     

Sodium Elimination Rate and Blood Pressure during Normal and High Salt Intake in Subjects with and without Familial Predisposition to Hypertension

Abstract We have assessed the elimination rate of ²²Na (ER-²²Na), total exchangeable sodium (Na^E), blood pressure, plasma volume (PV), haematocrit, urinary noradrenaline (U-NA) and urinary 3-methoxy-4-hydroxymandelic acid (U-VMA) in normotensive men with (n=17) and without (n=15) familial predisposition to hypertension. All measurements were done during habitual salt intake and after four weeks of increased salt intake (ordinary intake + 12 g NaC1/daily). On ordinary salt intake, ER-²²Na, Na^E, blood pressure, PV, haematocrit, U-NA and U-VMA did not differ between the groups thus indicating a normal sodium turnover in both groups and a comparable activity of the sympathetic nervous system. After 10 days of high salt intake those without familial predisposition showed signs of volume expansion and decreased sympathetic activity and those with such predisposition showed insignificant changes in the same direction. After four weeks of increased salt intake, ER-²²Na had increased significantly and equally in both groups, while blood pressure and Na^E remained unchanged. This indicates that the predisposed individuals had a normal ability to cope with a prolonged increase in salt intake.