Search PubMed⌕ Search

Biomedical subjects

G Stock

Publications and source records attributed to G Stock.

At least 37 records · Page 2Linked to original sources
PubMed1991

Potassium channel activation, hyperpolarization, and vascular relaxation.

1) Numerous compounds and changes in physical state functions shift the membrane potential of vascular smooth muscle to more negative values. The consequence is a vasodilatation because Ca2+ channels are closed. K+ channel opening frequently causes the hyperpolarization. 2) Acidification of the blood substitute solution, a fall in O2 partial pressure, and an increase in blood flow dilate arterial vessels. Acidosis is associated with a rise in K+ permeability and a simultaneous fall in Na+ permeability. Prostacyclin has a 20-30% share, and EDHF a 70-80% share in hypoxic vasodilatation. Experiments with iloprost (PGI2 analogue) confirmed the K+ channel opening properties of this drug. A voltage-dependent K+ channel and a Ca(2+)-activated K+ channel, via the influence of cA-PK or cG-PK, are responsible for the hyperpolarization with iloprost and with oxygen deficiency. 3) With 23Na+ nuclear magnetic resonance techniques, it has been demonstrated that with flow-dependent vasodilatation, proteoheparan sulphate integrated in the membrane of endothelial cells possibly served as a "flow sensor". With an external strain, such a compound can go from a randomly coiled state to an oriented state. Based on these viscoelastic properties, heparan sulphate proteoglycan is present as a random coil under "no flow" conditions and as an unfurled filament structure with increasing flow. This conformational change produces additional anionic binding sites to which Na+ ions of the blood are bound. A membrane hyperpolarization could be directly initiated by this Na+ binding via the protein fraction within the macromolecule or via a change in zeta-potential. Therefore, these ions can trigger the signal transduction for a vasodilatory vessel reaction. Decrease in flow is followed by a structural change of the macromolecule towards coil conformation, a release of Na+ ions and, thus, an interruption of the signal chain. 4) Cicletanine, aqueous garlic extract, and ajoene cause a concentration-dependent membrane hyperpolarization and are potent vasodilators. A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects. Under noradrenaline, the cicletanine effect is amplified. Aqueous garlic extract and ajoene exert a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 5) The stationary activation curve "developed force vs. membrane potential" satisfactorily explains the effects of K+ channel openers. The tight electromechanical coupling expressed by this curve comprises a 50% vasorelaxation for a 2.5 mV hyperpolarization. In the linear part of the curve, the coupling ratio is 5.1 mV/g.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Afferent connections of the nucleus centralis amygdalae. A horseradish peroxidase study and literature survey.

The central nucleus of the amygdala has been shown to be involved in cardiovascular regulation and the integration of arousal. In this study, the afferent input was investigated in cat by microinjecting horseradish peroxidase (HRP) into the central nucleus and examining retrogradely-labelled cells in the brain. Retrograde labelling was found in the cortex next to the sulcus ectosylvius anterior, fissura lateralis Sylvii, sulcus rhinicus anterior and posterior, sulcus suprasylvius, and pyriform and entorhinal cortices as well as in the insula and claustrum. Each of the sub-nuclei of the amygdaloid complex exhibited retrogradely-labelled perikarya. Labelled cells were also found in the diagonal band of Broca, nucl. lateralis septi, and nucl. proprius striae terminalis (bed nucl. of stria terminalis). In the hypothalamus the area preoptica medialis and lateralis, nucl. dorsomedialis, paraventricularis, periventricularis, arcuatus and mammilaris medialis were labelled. The nucl. subthalamicus, zona incerta, peripeduncular system, substantia nigra, and nucl. interpeduncularis contained HRP-marked cells. In the thalamus labelled cells were observed in the nucl. reuniens, nucl. centroposterior lateralis, nucl. latero-posterior, nucl. posterior, nucl. centro-anterior, antero-dorsalis, antero-medialis, antero-lateralis, centrum mdianum, nucl. reticularis, nucl. rhomboideus, nucl. parafascicularis and subfascicularis. The area tegmentalis Tsai and the corpora geniculata also contained labelled cells. In the brain stem, HRP-marked cells could be detected in the brachium colliculi inferioris, aqueductal grey matter, locus coeruleus, nucl. parabrachialis, in various nuclei of the formatio reticularis, in the nucl. retrofascialis, nucl. solitarius, nucl. commissuralis, nucl. ambiguus and nucl. dorsalis n. vagi. The results were compared to other neuroanatomical studies and to functional studies of the amygdala.

Afferent Pathways↗
PubMed1989

Prostacyclin, endothelium-derived relaxing factor and vasodilatation.

In arterial smooth muscle with normal tone or predepolarized and precontracted by noradrenaline, prostacyclin (10(-9) to 10(-6) M) effects a dose-dependent hyperpolarization and relaxation. The hyperpolarization is due to K+ channel opening. In hypoxic vasodilatation, which is likewise induced by membrane hyperpolarization, a share of 20% falls to prostacyclin and 80% to an endothelium derived hyperpolarizing factor.

Animals↗
PubMed1989

Vasorelaxation in prostacyclin-hyperpolarized arterial smooth musculature.

In arterial smooth muscle with normal tone or predepolarized and precontracted by noradrenaline, prostacyclin (10(-9) to 10(-6) M) effects a dose-dependent hyperpolarization and relaxation. The hyperpolarization is due to K+ channel opening. In this hyperpolarized portion of the stationary, sigmoid activation curve, vasodilation can be explained by means of Ca2+ channels that are closed between -40 mV and -80 mV in a voltage-dependent manner.

Animals↗
PubMed1989

Effect of the prostacyclin analogue iloprost on K+ permeability in the smooth muscle cells of the canine carotid artery.

The present contribution deals with the electro- and tracerphysiological correlations to vasodilatation observed under prostacyclin or O2 deficiency. Because of the extreme chemical instability of native PGI2, we used iloprost, a stable carbacyclin analogue. At concentrations between 10(-9) and 10(-6) mol/l, iloprost hyperpolarized the resting membrane of normal tone (V = -63.4 mV) and noradrenaline predepolarized vascular smooth muscle cells (V = -55.2 mV) of the canine carotid artery by 7.4 and 16.9 mV, respectively, in a concentration-dependent manner. Correspondingly, the isometric tension was decreased. In both experimental series, the half-maximal effect was attained at a concentration of 2 x 10(-8) mol/l. The coupling ratios developed tension versus membrane potential were 1.079 mV/mN in normal tone and noradrenaline treated preparations. Hyperpolarization and relaxation in the latter group, however, were much larger for the same iloprost concentrations. 42K+ efflux was stimulated by 250% with iloprost (10(-6) mol/l), whereas 24Na+ efflux was increased only by 50%. This resulted in an augmentation of K+ permeability by 340% and of Na+ permeability by 40%, respectively. The ratio PK/PNa rose from 16 to 49 with iloprost. These results lead to the conclusion that iloprost should be classified as a K+ channel opener.

Animals↗
PubMed1989

Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment.

The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.

Androgen Antagonists↗
PubMed1987

Sensory input to single neurons in the amygdala of the cat.

We determined functionally the afferent projections from exteroceptors and enteroceptors (visceral receptors) to single cells of the amygdala. Recordings were made in chloralosed cats from 249 cells in four subnuclei of the amygdala. Forty-six percent of cells tested responded to carotid sinus nerve stimulation and more than one-half of them responded to selective baroreceptor or chemoreceptor activation or to electrical stimulation of the locus ceruleus. Of 11 cells responding similarly (inhibition) to carotid sinus nerve stimulation and to selective baroreceptor activation, all were inhibited by locus ceruleus stimulation, also. Approximately 17% of cells tested responded to at least one exteroceptive stimulus (acoustic, optic, or tactile) whereas 14% responded to more than one exteroceptive stimulus in a similar manner. Amygdalar cells were also identified that responded to visceral (renal nerve) and somatic (iliac nerve) stimulation. Many cells received input both from enteroreceptors and from exteroceptors. These results suggest that baroreceptor input to single neurons in the amygdala is often convergent with input from the locus ceruleus. In addition, the convergence of both internal and external sensory inputs to single neurons is further evidence that the amygdala is a site for the integration of responses to arousal.

Acoustic Stimulation↗
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↗