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Biomedical subjects

I Hilakivi

Publications and source records attributed to I Hilakivi.

28 records · Page 2Linked to original sources

Effects of methoxamine, and alpha-1 adrenoceptor agonist, and prazosin, an alpha-1 antagonist, on the stages of the sleep-waking cycle in the cat.

In these experiments the effects of alpha 1-adrenoceptor agonism and antagonism were studied on the stages of the sleep-waking cycle of the cat, in order to determine optimal levels of alpha 1-adrenergic transmission for these stages. Polygraphic 16-h recordings showed that prazosin, an alpha 1-adrenoceptor antagonist, at 1 mg/kg i.p., increased paradoxical sleep (PS) time from 15.3% to 26.4% (p less than 0.001) of total time, and the number of PS episodes from 30.4 to 43.6 (p less than 0.001). The effect was prompt, reaching a maximum during the first 4 h with a shortening of PS latency from 40.4 min to 11.0 min (p less than 0.001). Prazosin at doses of 0.5 and 3.0 though not at 10.0 mg/kg also slightly, but significantly, increased PS. Methoxamine, and alpha 1-adrenoceptor agonist, at doses of 0.5 and 3.0 mg/kg, increased aroused waking time (low voltage mixed frequency EEG) during the first 4 h from 23.5% to 33.3% (p less than 0.05) and to 50.3% (p less than 0.01), and decreased PS. Prazosin potentiated dose-dependently clonidine-induced drowsiness ( hypersynchronized 4-8 Hz EEG), whereas the decrease in deep slow wave sleep and PS were potentiated only at the largest dose of it. These results indicate that moderate inhibition of cerebral alpha 1-adrenergic transmission facilitates paradoxical sleep in the cat. Furthermore, they suggest that the level of cerebral alpha 1-adrenergic transmission is high during aroused waking and low during drowsy waking.

Adrenergic alpha-Agonists↗

The role of beta- and alpha-adrenoceptors in the regulation of the stages of the sleep-waking cycle in the cat.

The effects of beta-adrenergic drugs alone and in combination with alpha-adrenergic drugs on the stages of the sleep-waking cycle were studied in adult cats. Polygraphic sleep recordings of 16 h showed that prenalterol (20 and 40 mg/kg i.p.), a beta 1-adrenoceptor-stimulating drug increased paradoxical sleep (PS) in a dose-related manner during 4-12 h. Salbutamol (40 mg/kg), a beta 2-adrenoceptor-stimulating drug, decreased PS during the first 4 h. Metoprolol (10 and 50 mg/kg), a relatively selective beta 1-adrenoceptor blocking drug, increased drowsy waking during the first 4 h. The larger dose also tended to decrease PS. Already at the lower dose metoprolol partially antagonized the PS increase produced by prazosin, an alpha 1-adrenoceptor blocking drug. Propranolol (5 mg/kg), a beta 1- and beta 2-adrenoceptor blocking drug, which alone decreases PS, antagonized the PS increase induced by phentolamine, an alpha 1- and alpha 2-adrenoceptor blocking drug. Atenolol (5 mg/kg), a poorly lipid-soluble beta-adrenoceptor blocking drug, failed to counteract phentolamine in increasing PS. Metoprolol (10 and 50 mg/kg) and propranolol (5 mg/kg) clearly potentiated the increase in drowsy waking and decrease in deep slow wave sleep and PS induced by clonidine (0.01 mg/kg), an alpha 2-adrenoceptor-stimulating drug. The results support the involvement of beta-adrenoceptors in the regulation of the sleep-waking cycle. A high level of beta-adrenergic activity may facilitate the production of PS. A low level of beta-adrenergic activity, especially in combination with a high level of alpha 2-adrenergic activity, may facilitate the production of drowsy waking. Central alpha 1- and beta 1-adrenoceptors may mediate opposite functions in the regulation of PS.

Albuterol↗

Sleep disorders in relation to coronary heart disease.

In a cross-sectional study of 5419 Finnish adult men, a higher prevalence of diagnosed myocardial infarction was found among those who slept more than 9 hours, whilst those sleeping less than 6 hours per night had more symptomatic coronary heart disease (CHD). This relationship held after controlling by multivariate analysis for age, sleep quality, use of sleeping pills and tranquilizers, smoking, alcohol use, Type A score, neuroticism, use of cardiovascular drug and history of hypertension. The cardiovascular physiology and pathophysiology of sleep is reviewed and the relationship of some specific sleep disorders to CHD is discussed.

Adult↗

Prazosin increases paradoxical sheep.

Prazosin 0.5 and 1.0 mg/kg i.p. induced a prompt and enduring increase in paradoxical sleep in the cat. The maximal effect, 140 percent above control was observed during the first 4 h after 1 mg/kg. In 16 h polygraphic records the respective increment was 69%. After 10 mg/kg paradoxical sleep was inhibited but it returned to control levels in 16 h. These results are discussed with reference to our previous experiments with agents having different alpha 1- and alpha 2-antagonist or agonist potency. It is concluded that selective, moderate blockade of alpha 1-receptors favours paradoxical sleep.

Animals↗

Effects of two adrenergic beta-receptor blockers on the sleep cycle of the cat.

Sixteen hour polygraphic recordings (EEG, EOG and EMG) were obtained from 14 adult cats after intraperitoneal injections of propranolol (5 mg/kg) or pindolol (0.1 or 0.5 mg/kg). All injections moderately increased waking, which consisted mainly of a sedated drowsy stage. Both drugs also decreased deep slow wave sleep, while light slow wave sleep remained at control levels. The changes were more marked after propranolol, which also significantly reduced paradoxical sleep (PS). The decrease in the deeper stages of sleep and PS is suggested as being due to blockade of the central adrenergic beta-receptors per se and/or antagonistic effects of the beta-blockers on 5-HT receptors. The results agree with the finding that beta-blockers cause insomnia in susceptible patients, but they do not suggest that intensified dreaming or nightmares reported by others are likely to be caused by increased PS.

Adrenergic beta-Antagonists↗

Effect of peripheral administration of arginine vasotocin on neonatal sleep in rats.

Vasotocin was recently reported to increase the neonatal amount of active sleep in kittens. In this study we examined the effects of arginine vasotocin (vasotocin), given intraperitoneally and at a wide dose range, on the sleep-wake behavior of 7-day-old and 14-day-old rat pups using a static charge sensitive recording system. It increased the percentage of quiet state relative to total sleep time at the doses of 0.01-1.0 ng/g of body weight but did not affect it at the dose of 0.001 ng/g. The percentage of active sleep was decreased by doses of 0.01-10.0 ng/g. The increase in the amount of quiet state and the concurrent suppression of active sleep lasted for 6 hours. Wakefulness was slightly increased at 10 ng/g of vasotocin. These findings indicate that, in contrast to the reports on kittens, in newborn rats peripheral administration of vasotocin increases the amount of quiet state relative to total sleep time and decreases that of active sleep.

Aging↗

Effect of beta-casomorphin on neonatal sleep in rats.

The effects of bovine beta-casomorphin(1-7) (Tyr-Pro-Phe-Pro-Gly-Pro-Ile) on neonatal sleep in rats were studied. The pups received intraperitoneal injections of beta-casomorphin(1-7) (1 mg, 5 mg, 10 mg, 50 mg, or 100 mg/kg) or a corresponding volume of sodium chloride. In any of the doses used, beta-casomorphin(1-7) had no effect on waking. Only 100 mg/kg caused significant changes in sleep: the percentage of quiet state of the total recording time (TRT) increased and the percentage of active sleep decreased. Beta-casomorphin(1-7) did not cause significant respiratory depression. Naloxone pretreatment (1 mg/kg IP) reversed the effects of beta-casomorphin(1-7) on sleep, a finding which suggests that opiate mu-receptors are involved in mediating the sleep effects of beta-casomorphin.

Amino Acid Sequence↗

Effect of desipramine during infancy and preweanling on dorsal striatal dopamine D1 and D2 receptor binding in adolescence in the rat.

Desipramine, a monoamine uptake inhibiting antidepressant, was given once a day sc from the 6th to the 22nd postnatal days, which is during infancy and preweanling in ontogenesis, to rats and its effects on dorsal striatal dopamine D1 and D2 receptor binding in adolescence were examined. The rats were decapitated, their dorsal striata were dissected on approximately the 34th postnatal day, and the maximal densities (Bmax) and affinities (Kd) of dopamine D1 and D2 receptors were assayed using [3H] SCH 23390 and [3H] spiperone as ligands. Desipramine did not affect the densities or affinities of dopamine D1 or D2 receptor binding, and tended to increase the D1/D2 density ratio. The Bmax of dopamine D2 receptors was higher in male than in female rats (p<0.01), the D1/D2 Bmax ratio tended to be lower in male than in female rats (p<0.07), and the Kd for D1 receptors tended to be lower in male than in female rats (p<0.05). There was no interaction between treatment and gender. We conclude that desipramine given at infancy and preweanling increases the susceptibility of adolescent rats to behavioral effects of dopamine agonists with an optimal, and relatively high SCH 23390/spiperone binding site density ratio. Furthermore, gender differences in dorsal striatal spiperone binding site densities, SCH 23390/spiperone density ratio, and SCH 23390 affinities may render male rats more vulnerable than female rats to expression of excessive stereotyped behavior.

Adrenergic Uptake Inhibitors↗

Administration of desipramine at infancy reduces dorsal striatal serotonin metabolism at adolescence in the rat.

Desipramine, a monoamine uptake inhibiting antidepressant, was given at infancy to male and female rats and the effects of its administration on the metabolism of dorsal striatal monoamines at adolescence were examined. Desipramine, 5 mg/kg s.c., was administered once a day from the 6th to the 20th postnatal day. Rats were decapitated at the postnatal age of one month and the concentrations of monoamines and their metabolites in dorsal striata were analyzed using high performance liquid chromatography with electrochemical detection. Desipramine decreased the concentration of 5-hydroxyindole-acetic acid by 22%. Other monoamines, their metabolites or metabolite/monoamine ratios were not affected. We conclude that desipramine given systemically at infancy reduces dorsal striatal metabolism of serotonin at adolescence in the rat.

Animals↗