Obesity and hypertestosteronaemia are independently and synergistically associated with elevated insulin concentrations and dyslipidaemia in pre-menopausal women.

The association of obesity and hypertestosteronaemia with elevated insulin concentration and dyslipidaemia was studied in 15 non-obese and 15 obese, hypertestosteronaemia patients; 14 non-obese and 10 obese, normotestosteronaemic subjects served as controls. Data were subjected to multivariate analysis. Enhanced body mass index (BMI kg/m2) resulted in a significant elevation of basal insulin (b-Ins), glucose-stimulated (delta) insulin (del-Ins), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and LDL/high density lipoprotein (HDL) ratio, and in a significant reduction of HDL. Furthermore, it was shown that BMI was positively correlated with TG, VLDL, LDL and LDH/HLD ratio, and negatively correlated with HDL in the normotestosteronaemic groups. Hypertestosteronaemia was associated with a significant increase of del-Ins, VLDL and LDL/HDL ratio, and with a significant decrease of HDL concentration. Testosterone was directly associated with del-Ins and LDL/HDL ratio, and inversely related to HDL in the non-obese groups. Summation effects of obesity and hypertestosteronaemia were found for del-Ins and VLDL. The data suggest that obesity and hypertestosteronaemia are independently and jointly associated with insulin resistance and dyslipidaemia, indicating an increased risk for coronary heart disease. The highest risk rate was found in obese hypertestosteronaemic patients. Serum testosterone may be a useful marker in detecting metabolic disorders connected with cardiovascular risk.

Inhibition via opioid mu- and delta-receptors of vagal transmission in rabbit isolated heart.

The nervi vagi of isolated perfused rabbit hearts were stimulated by 10 s trains of electrical pulses at 1, 2 or 5 Hz. Morphine, Met-enkephalin and D-Ala2,D-Leu5-enkephalin reduced the ensuing bradycardia with IC50 values of 148, 25 and 3.2 nM, respectively. Naloxone antagonized the effects of morphine and Met-enkephalin; KB values (dissociation constants of antagonist-receptor complex) were 1.1 and 33 nM, respectively. The delta-receptor-selective antagonist ICI 174864 antagonized Met-enkephalin, KB 28 nM, but at 0.2 microM did not antagonize morphine. It is concluded that vagal transmission to the rabbit heart can be inhibited by activation of both opioid mu- und delta-receptors.

Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers.

Rat occipital cortex slices were preincubated with [3H]noradrenaline and then superfused with medium containing 30 micrometer cocaine. They were stimulated electrically at 3 Hz. Unlabelled noradrenaline (0.1 micrometer), alpha-methyl-noradrenaline (0.01-0.1 micrometer), xylazine (0.1-10 micrometer) and guanabenz (0.01 micrometer) decreased, whereas yohimbine (0.01-1 micrometer), rauwolscine (0.01-1 micrometer), corynanthine (10 micrometers), tolazoline (0.1-10 micrometers) and azapetine (0.1-1 micrometer) increased the stimulation-evoked overflow of tritium without a change in basal outflow. Pseudoyohimbine and prazosin at up to 0.1 micrometer did not change the evoked overflow, and a higher concentrations enhanced the basal outflow of tritium. In vivo, yohimbine 10 mg/kg and rauwolscine 10 mg/kg markedly, and corynanthine 10 mg/kg slightly accelerated the alpha-methyltyrosine-induced disappearance of noradrenaline from rat whole brain. Yohimbine and rauwolscine but not corynanthine also accelerated the alpha-methyltyrosine-induced depletion of dopamine. The results add four compounds to the list of drugs with alpha-adrenoceptor affinity which inhibit (agonists) or facilitate (antagonists) action-potential-evoked release of noradrenaline in rat brain cortex. The presynaptic receptors are of the alpha 2-type. The receptors which control the activity of noradrenaline and dopamine neurons in vivo also appear to be alpha 2.

gamma-Aminobutyric acid and postganglionic sympathetic transmission in the pulmonary artery of the rabbit.

1 The effect of gamma-aminobutyric acid (GABA) on postganglionic sympathetic neurotransmission was studied in strips of the rabbit pulmonary artery. The strips were preincubated with 3H-noradrenaline and then superfused with 3H-amine-free medium. They were stimulated either electrically at 2 Hz, or by 60 mM potassium, or by 1 microM tyramine. 2 GABA (1 - 1000 microM) did not change the basal outflow of tritium, but decreased the electrically evoked overflow as well as the contractile response. GABA 1 microM decreased the evoked overflow by 12%, and GABA 1000 microM, by 42%. The effect of GABA was not changed by yohimbine, propranolol, cocaine, corticosterone, or indomethacin. It was not antagonized by picrotoxin or bicuculline methiodide. GABA 100 microM also slightly reduced the potassium-evoked overflow of tritium but did not change the tyramine-evoked overflow. 3 The results show that, in the pulmonary artery of the rabbit, GABA inhibits the release of noradrenaline. Its effect is independent of alpha- and beta-adrenoreceptors and is not mediated by prostaglandins. The effect may be due to activation of presynaptic receptors which appear to differ from conventional GABA receptors inasmuch as they are insensitive to blockade by either picrotoxin or bicuculline.

Effects of prostaglandin E2, prostaglandin I2 and 6-keto-prostaglandin F1 alpha on adrenergic neurotransmission in the pulmonary artery of the rabbit.

Strips of the rabbit pulmonary artery were preincubated with 3H-noradrenaline and then superfused and stimulated electrically at 2 or 4 Hz. PGE2 and PGI2 reduced the stimulation-evoked overflow of total tritium and 3H-noradrenaline. PGI2 was about 10 times less potent than PGE2. High concentrations of 6-keto-PGF 1alpha also diminished the evoked overflow, but the effect was small. It is concluded that PGI2, in comparison with PGs of the E series, is a relatively weak inhibitor of noradrenaline release.

[Prostaglandin-F-levels in human plasma during late pregnancy and labour (author's transl)]. / Prostaglandin-F-Spiegel im menschlichen Plasma während der späten Schwangerschaft und während der Wehentätigkeit

The concentrations of prostaglandin F-equivalents were measured in peripheral plasma during labour at a cervical dilatation of 5 cm and at complete dilatation. After purification, extraction and chromatography the PGF-equivalents were measured radioimmunologically. The intraassay variation was 1.5%, the interassay variation 3.5%. The specificity for PGF was 96-98%. Logit/log transformation of the standardcurve yielded a sensitivity of the assay of 120 pg. At cervical dilatation of 5 cm PGF-equivalents varied between 1300 and 3200 pg/ml plasma. At complete dilatation values changed between 1200 and 5400 pg/ml. These fluctuations correlate timedepending to the uterine contractions recorded and may be interpreted as a result of uterine PGF-release.