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Biomedical subjects

G Stock

Publications and source records attributed to G Stock.

At least 55 records · Page 3Linked to original sources
PubMed1987

Atrial natriuretic factor inhibits central angiotensin II pressor responses.

Intracerebroventricular (i.c.v.) administration of human atrial natriuretic factor (ANF), fragment 1-25, in the dose range 3 to 20 micrograms/kg did not alter resting arterial pressure or heart rate in rats anesthetized with chloralose/urethan (60:600 mg/kg i.p.), while angiotensin II (ANG II), 1 microgram/kg, produced a significant increase in arterial pressure after i.c.v. application. This pressor effect induced by ANG II was abolished by simultaneous administration of ANF (3 micrograms/kg i.c.v.). In isolated strips of rabbit aorta preconstricted with ANG II (10 nM), ANF caused a dose-dependent relaxation. In intact rats, the increase in blood pressure following intravenously administered ANG II (0.1 and 1 microgram/kg) was not altered by the highest dose of ANF (20 micrograms/kg) given intracerebroventricularly. These results suggest that atrial peptides may play an important role in the regulation of blood pressure by interacting with both the central and peripheral actions of ANG II. Inhibition of the central pressor action of angiotensin by ANF appears to be independent of any direct peripheral effect of the atrial peptides.

Angiotensin II↗
PubMed1987

Angiotensin II-induced vasopressin release is attenuated by central atrial natriuretic factor.

Administration of angiotensin II (Ang II) into the cerebral ventricles (icv) of rats elicits vasopressin release and an increase in blood pressure. The effect of atrial natriuretic factor (ANF) on these actions of ANG II was studied in conscious spontaneously hypertensive rats. The magnitude and time course of the blood pressure increase following ANG II (50 and 100 ng) were not altered by ANF, icv. However, vasopressin levels which were stimulated from 10.8 +/- 1.5 to 62.1 +/- 6.4 pq/ml by ANG II (100 ng) were significantly suppressed by combined administration of ANG II (100 ng) and ANF (3 ug/kg) (33.0 +/- 4.3 pg/ml). The injection of ANF alone into the cerebral ventricles had no effect on resting blood pressure or vasopressin levels. Peripheral administration of ANF was unable to attenuate the ANG II-induced vasopressin release. These data suggest that there exists a central interaction of ANF and ANG II within the brain which cannot be mimicked by peripheral administration of ANF.

Angiotensin II↗
PubMed1987

Amygdala neurons influence cardiovascular reactions preceding psychomotor behavior.

In unanesthetized chronically instrumented cats single neuron discharges were recorded in the amygdaloid complex together with blood pressure, heart rate (HR), EEG, and motor activity. In response to complex sensory stimuli neuronal activity changed followed by blood pressure changes preceding the arousal reaction. Besides the impact of neuronal discharges on the cardiovascular system, the neurons in turn received an input from the cardiovascular system. It is hypothesized that an exaggerated reactivity of amygdala neurons to complex sensory stimuli can lead to high blood pressure.

Amygdala↗
PubMed1986

Baroreceptor sensitivity during desynchronized sleep.

Sleep is characterized by periods of cortical and subcortical desynchronization similar to that observed during arousal. Because baroreflex control of heart rate is suppressed in the aroused state, the present study compared the cardiac index of baroreflex sensitivity in awake cats with that during desynchronized sleep to determine the level of arousal and its affect on autonomic regulation. Cats were prepared for long-term arterial pressure, cortical, and subcortical EEG and EMG recording. After acclimatization to the laboratory, cats engaged in spontaneous periods of desynchronized sleep. During this period, a bolus of angiotensin II was injected i.v. and the subsequent change in the R-R interval of the cardiac cycle was recorded during the rising phase of the pressor response. These values were compared with values obtained from the same cats during quiet and active wakefulness and those obtained during drug-induced desynchronized sleep with gamma-hydroxybutyrate. The values obtained during naturally occurring desynchronized sleep were comparable to those observed during drug-induced desynchronized sleep. In contrast, the increase in the R-R interval in awake cats, particularly quiet ones, was greater than that seen during desynchronized sleep or during active periods in the awake animal. These data suggest that there is a correlation between the level of arousal, as measured by EEG activity, and the cardiomotor component of baroreflexes.

Animals↗
PubMed1986

Pharmacological profile of a novel carbacyclin derivative with high metabolic stability and oral activity in the rat.

A novel carbacyclin derivative (16S)-13,14-dehydro-16,20-dimethyl-3-oxa-18,18,19,19-tetradehydro- 6a- carbaprostaglandin-I2 (3-oxa-analogue) has been synthesized in order to find chemically and metabolically stable prostacyclin-mimetics with a potency equal or even superior to PGI2. The 3-oxa-analogue was found to be stabilized against beta-oxidation, a main metabolic degradation step also for chemically stable PGI2-analogues. The compound is orally available and displays a long duration of 4.5-48 h of antiaggregatory and hypotensive action. The 3-oxa-analogue inhibits ADP-induced platelet aggregation with an IC50 of 3.0 nM. Following intravenous application the 3-oxa-analogue lowers diastolic blood pressure in a dose dependent manner, the ED20 being 0.1-0.2 micrograms/kg after injection and less than or equal to 0.05 micrograms/kg/min after infusion respectively. In vivo platelet aggregation is inhibited after i.v. infusion of the 3-oxa-analogue with an IC50 of 0.037 micrograms/kg/min. As compared to Iloprost, the 3-oxa-analogue is 5-12 fold more potent with respect to in vivo hypotensive and anti-aggregatory effects. The results of the present studies indicate that the 3-oxa-analogue has a pharmacological profile comparable to prostacyclin (PGI2) and Iloprost. Due to the fact that the 3-oxa-analogue is chemically and metabolically stable, long term oral treatment can be achieved in clinical conditions in which PGI2 and Iloprost have already been shown to be therapeutically useful principles.

Administration, Oral↗
PubMed1986

Pharmacological studies on the intrinsic sympathomimetic activity of the beta-adrenoceptor antagonist mepindolol.

1-Isopropylamino-3-(2-methyl-4-indolyloxy)-2-propanol (mepindolol, Corindolan) is a beta-adrenoceptor antagonist with significant intrinsic sympathomimetic activity (ISA): positive chronotropic effects in atria of the rat amount to 24% of those elicited by the full agonist isoprenaline. Relaxant effects in blood vessels approach 50% of those of isoprenaline. This vasorelaxant effect is completely blocked by the specific beta 2-adrenoceptor antagonist ICI 118 551 (erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobut an-2-ol), suggesting that the vasodilatory effects of mepindolol are elicited by stimulation of vascular beta 2-adrenoceptors. In the anaesthetized cat mepindolol acutely lowers arterial blood pressure by reducing total peripheral resistance without exhibiting significant cardiodepressant action, whereas propranolol, lacking ISA, lowers blood pressure by a marked reduction of cardiac output and left ventricular contractility, however, total peripheral resistance is significantly increased.

Adrenergic beta-Antagonists↗
PubMed1986

[Diagnosis and treatment of cardiac rhabdomyomas].

A diagnosis of primary cardiac tumors was achieved by two-dimensional echocardiography in 3 patients. Two of them were female neonates, born of the 29th and 40th gestational week who had shown intrauterine arrhythmias. Subsequently, we were able to diagnose tuberous sclerosis in both. The third child, a 121/2 year old boy, with already diagnosed tuberous sclerosis, presented an electrocardiographical preexcitation syndrome. Because of the multiplicity of the tumors and the association with tuberous sclerosis we presumed that the tumors were rhabdomyomas. As it is known that rhabdomyomas show no, or only a minimal postnatal growth, we decided neither to perform a heart catheterization nor to treat them surgically unless the children show hemodynamical deterioration, although the tumors were huge in both neonates. The subsequent 14 months showed a clear regression in the size of the tumors. One of the neonates was successfully treated with amiodarone because of ventricular tachycardia. The second neonate didn't require any treatment. We conclude that: Surgical management is only necessary in patients presenting with cardiac insufficiency and/or arrhythmias that are resistant to conventional medical treatment. Primary cardiac tumors should be looked for in patients presenting with arrhythmias, even when occurring already during intrauterine life. Diagnostic measures in order to diagnose tuberous sclerosis in patients with cardiac tumors are necessary and vice versa.

Adolescent↗
PubMed1984

Baroreceptor reflex during arousal induced by electrical stimulation of the amygdala or by natural stimuli.

Baroreceptor control of heart rate was studied in 14 unanaesthetized cats during rest and arousal induced by either electrical stimulation of the central nucleus of the amygdala or by natural stimuli. The baroreceptor reflex was elicited by i.v. injections of angiotensin II and the sensitivity of the vagal component of the reflex expressed as the regression coefficient of the relationship between the systolic blood pressures of successive arterial pulses and their pulse intervals. Baroreceptor reflex sensitivity was reduced by all types of arousing procedure studied; an effect assumed to be a part of integrated cardiovascular adjustments accompanying arousal. Further studies in slightly anaesthetized cats were performed in order to investigate the time-course of such changes in reflex sensitivity. Th inhibition of the vagal component of the reflex did not last for the entire period of the electrically elicited arousal and it is suggested, therefore, that this might reflect the activation of mechanisms which limit orienting behaviour. Overall, these results indicate that the central nucleus of the amygdala may be involved in a transient integration of cardiovascular and behavioural responses during arousal.

Amygdala↗
PubMed1983

Monoamine metabolites in the CSF of conscious unrestrained cats.

The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured repeatedly over a period of up to 5 months at different sites of the brain ventricular system in unrestrained, awake cats. Samples of 10 microliter CSF were analyzed by high pressure liquid chromatography and subsequent electrochemical detection. Concentrations were in the range of 30-130 ng/ml for DOPAC, 110-340 ng/ml for 5-HIAA and 180-750 ng/ml for HVA. The monoamine metabolites were constant even over a period of several months if measured in the same animal but there was a marked interindividual variation. A marked gradient for monoamine metabolites was found when CSF samples from frontal sites of the lateral ventricle were compared to CSF samples from the dorsal lateral ventricle. The concentrations of DOPAC and HVA were higher at frontal sites.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Involvement of dopamine in amygdaloid kindling.

The concentrations of dopamine, noradrenaline, and dihydroxyphenylacetic acid were determined in the amygdala, neostriatum, neocortex, hippocampus, brain stem, and hypothalamus of cats, which had had 9 to 14 tonic-clonic kindled seizures. No significant biochemical changes were observed compared to control cats. Pharmacological manipulations of dopamine receptors (haloperidol, apomorphine) did not modify the kindling procedure. According to the data it seems unlikely that dopamine plays a major role in amygdaloid kindling.

Amygdala↗
PubMed1981

Cardiovascular changes during arousal elicited by stimulation of amygdala, hypothalamus and locus coeruleus.

Experiments were performed in chronically operated cats first awake and thereafter anesthetized with pentobarbitone, 16-20 mg/kg i.v. Stimulation of the central amygdala in awake cats elicited an arousal reaction seen in cortical and hippocampal EEG, and in muscle activity of dorsal neck muscles. Concomitantly therewith were autonomic system reactions resulting in a decrease in aortic blood flow distal to the renal arteries, an increase in arterial blood pressure, a tachycardia during, and a short-lasting bradycardia at the end of stimulation. In slightly anesthetized cats the cardiovascular reactions were found to be qualitatively similar. If the postero-lateral hypothalamus or the locus coeruleus complex were stimulated in cats first awake and thereafter anesthetized, similar arousal reactions and similar cardiovascular changes were obtained as with amygdaloid stimulations. However, the onset and magnitude of the response were more abrupt and more marked than those obtained by amygdaloid stimulations. Recordings of single unit activity within the central amygdala during spontaneously occurring changes in the level of arousal showed that amygdaloid units (n = 10) discharged at a rate of 7-14 impulses/sec during wakefulness whereas during slow wave sleep (n = 5) the discharge was only 2-9 impulses/sec. The hypothesis is put forward that the amygdala integrates behavioral and cardiovascular changes during arousal.

Amygdala↗
PubMed1981

Long-term application of haloperidol: effects on dopamine and acetylcholine receptors.

Rats were injected daily with haloperidol, 0.5 mg/kg i.p., or pimozide, 2 mg/kg i.p., for a period of 8 or 16 days, respectively. 24 h after the last injection of haloperidol, these rats were challenged with gamma-butyrolactone (GBL) in doses of 200-750 mg/kg i.p. In haloperidol-treated rats, higher doses of GBL are needed in order to increase the rate of dopa accumulation. This finding demonstrates the development of supersensitivity of dopamine (DA) autoreceptors towards endogenously released DA. Pimozide had no effect on the increased rate of dopa accumulation induced by increasing doses of GBL. From this data it is concluded that pimozide in our model is mainly active on postsynaptic DA receptors and haloperidol is active on pre- and postsynaptic DA receptors. In rats treated chronically with daily injections of haloperidol, benztropine, in a dose of 50 mg/kg, induced a decrease in dopa accumulation which was more marked than the decrease seen with benztropine, 50 mg/kg in animals treated with a single injection of haloperidol only. The opiate antagonist, naloxone at a dose of 10 mg/kg, had no effect on these results. Benztropine, 50 mg/kg i.p., had no effect on the increased rate of dopa accumulation induced by GBL, 400 mg/kg. The data support the hypothesis that in parallel to the development of supersensitive postsynaptic DA receptors, there is a development of subsensitivity in cholinergic receptors within the nigro-neostriatal system. Further the results show that a new DA-acetylcholine equilibrium is reached during long-term haloperidol treatment. The implications of these findings in regard to extrapyramidal side effects during long-term neuroleptic treatment are briefly discussed.

4-Butyrolactone↗
PubMed1980

Supersensitivity of dopamine-autoreceptors. The effect of gammabutyrolactone in long-term haloperidol treated rats.

Rats were injected daily with haloperidol, 0.5 mg/kg i.p. for a period of 16 days. 24 hours after the last injection of haloperidol these rats were challenged with gammabutyrolactone in doses of 200-750 mg/kg i.p. The ensuing increase in neostriatal dopa-accumulation was significantly lower than in rats not previously treated with haloperidol. Since the increase in dopa-accumulation following GBL-treatment is most probably independent of postsynaptically located DA-receptors the difference between the experimental series is explained in terms of reduced feedback activation of DA-synthesis due to the increased sensitivity of presynaptically located DA-autoreceptors.

4-Butyrolactone↗
PubMed1980

Renin-like immunocytochemical activity in the rat and mouse brain.

Renin-like immunoreactivity could be demonstrated in the nuclei paraventricularis, periventricularis and supraopticus of the hypothalamus and in the cerebellar cortex of rats and mice, with both the peroxidase-antiperoxidase (PAP) and fluorescence techniques. The findings are consistent with the assumption of an endogenous angiotensin-forming system in the brain.

Animals↗