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G Stock

Publications and source records attributed to G Stock.

At least 19 recordsLinked to original sources

Responses of single neurons in amygdala to interoceptive and exteroceptive stimuli in conscious cats.

The amygdala is critical for behavioral arousal and must therefore integrate a wide variety of inputs. We examined sensory inputs and the degree of convergence to single neurons in the amygdala in conscious freely moving cats. A pressor stimulus elicited responses, predominantly inhibitory, in one-half of the amygdalar neurons tested. Most neurons in the central and basal nuclei responded to carotid chemoreceptor activation typically with an excitation. Almost one-half of all amygdalar neurons tested, particularly in the central nucleus, received orthodromic input from the locus ceruleus, the substantia nigra, and/or the contralateral central nucleus of the amygdala. Exteroceptive sensory stimulation with optic, acoustic, tactile, and olfactory stimuli elicited responses in 33, 55, 39, and 59% of amygdalar neurons, respectively. Two-thirds of the neurons tested with more than one external stimulus modality responded in the same manner to the various stimuli (usually excitation), demonstrating a convergence of exteroceptive stimuli on single amygdalar neurons, particularly in the basal nucleus. Spontaneous and induced behavioral arousal elicited responses in 92 and 86% of neurons, respectively. Most neurons responded to multimodal exteroceptive stimuli and behavioral arousal in the same manner. We suggest that amygdalar inputs are highly varied and, in many cases, relatively nonspecific and that the amygdala integrates a large number of external and internal sensory modalities to regulate autonomic and behavioral responsiveness to various stimuli.

Amygdala

Orthostatic challenge during neuroleptic test dose: a possible predictor of short-term outcome.

Cardiovascular measurements were used as indicators of autonomic arousal during an orthostatic challenge test without medication and after a test dose of 150 mg perazine in 20 acute schizophrenic patients. Unmedicated schizophrenics showed elevated heart rates and elevated systolic and diastolic blood pressure in comparison to healthy volunteers. After a test dose of 150 mg perazine, responders (using BPRS outcome criteria after 23 days) showed a pronounced orthostatic heart rate reaction in comparison to nonresponders. Results are discussed in relation to arousal theories and central dopaminergic activity in schizophrenia.

Adult

Potassium channel activation in vascular smooth muscle.

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 and a fall in O2 partial pressure 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. Cicletanine 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. Ajoene exerts a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 4. 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. 5. In the vascular smooth muscle, vasorelaxation can be evoked by membrane hyperpolarization which is linked to a simultaneous increase in K+ outward current and 42K+ efflux. In the case of substances whose influence is solely or partially receptor-mediated, cyclic nucleotides may be involved in vasorelaxation. Since cyclic nucleotides also hyperpolarize through an increase in K+ conductance, the resulting dilatation often cannot be divided into its single components. Therefore, it is sensible not to give the term "K+ channel opener" too fine a definition. The term should be applied to all substances and changes in physical states which predominantly increase the open probability of K+ channels finally via a conformational change in the cell membrane. For example, giving an acidic blood substitute solution (acidosis) is an intervention opening K+ channels. Which K+ channel and which single channel conductance is concerned in a particular case, and which 'mediator' may participate, become secondary questions.

Animals

Influence of different progestogens on blood pressure of non-anaesthetized male spontaneously hypertensive rats.

The aim of the study was to find out if synthetic progestins with significant antimineralocorticoid activity would have a beneficial effect on blood pressure. Male spontaneously hypertensive rats were treated daily for four weeks with different progestogens by subcutaneous injection. Arterial pressure of the conscious animals was measured at three-day intervals. Progestogens were dosed on the basis of their progestogenic activity, whereby the dosages corresponded to the 10-fold effective dose for inhibition of ovulation in rats. For comparison, spironolactone as well as progesterone itself were included in the study. After four weeks' treatment, plasma volume, extracellular fluid volume (ECFV) and the sodium and potassium concentrations in the plasma were measured. In control animals, there was a slight decrease in blood pressure over the four-week experimental period. Progesterone and spironolactone similarly influenced blood pressure. A new progestin with significant antialdosterone activity, dihydrospirorenone (code No. ZK 30.595), slightly but significantly decreased the ECFV, plasma sodium concentration and slightly but insignificantly decreased blood pressure as compared to vehicle-treated controls. Synthetic progestins lacking this antimineralocorticoid activity did not decrease blood pressure, but rather induced a slight increase in this animal model. The results clearly support the hypothesis that synthetic progestins, like endogenous progesterone, all of them with inherent antialdosterone activity, decrease the ECFV and so might have an impact on extracellular fluid hemostasis as well as blood pressure regulation.

Animals

Lovastatin in the treatment of hypercholesterolemia in CAPD.

The authors studied the effect of lovastatin on five hypercholesterolemic CAPD patients with high risk of atherosclerotic cardiovascular disease. Patients took lovastatin 20 mg once daily for a mean period of 4.5 months. Pre- and post-treatment values of LDL and VLDL totals (325 mg/dl and 292 mg/dl, respectively) and of HDL (42 mg/dl and 43 mg/dl, respectively) had no significant statistical difference. Lack of significance may be due to low number of patients and short trial time. The study did demonstrate that lovastatin is well tolerated in CAPD patients.

Adult

Sexual dimorphism of blood pressure: possible role of the renin-angiotensin system.

The prevalence of hypertension in men is higher than in women and the onset of this disease is earlier in male than in female subjects. In spontaneously hypertensive rats, males also have higher blood pressures than females. Evidence from epidemiological, physiological, molecular biological and morphological studies concerning this sexual dimorphism is reviewed. We demonstrate that the gonadal steroids testosterone and estrogen have important effects on the gene regulation of the renin-angiotensin system. This may in part contribute to the sexual dimorphism in blood pressure control. The direct effect of steroid hormones on genes related to hypertension provides a suitable paradigm to improve our understanding of molecular and cellular mechanisms of cardiovascular control.

Angiotensin II

Increased sensitivity to arousal in spontaneously hypertensive rats is partially dependent upon the amygdala.

This study was designed to determine the effects of behavioral arousal on baroreflex regulation of heart rate in stroke-prone SHR (spSHR) and to ascertain whether the integrity of the amygdala is necessary to mediate these effects. Heart rate responses to phenylephrine-induced increases in arterial pressure were used as an index of baroreflex sensitivity (BRS). spSHR had reduced BRS compared to WKR. Electrical stimulation of the amygdala suppressed BRS in conscious rats only at intensities that elicited behavioral arousal. When normalized for control bradycardiac responses, the spSHR demonstrated a greater suppression of BRS upon amygdalar stimulation than Wistar-Kyoto rats (WKR). Confrontation with a mouse, used to elicit behavioral arousal, attenuated BRS in both spSHR and WKR. Ablation of the central nucleus of the amygdala and adjacent tissue prevented confrontation-induced suppression of BRS both in WKR and spSHR. These data suggest that spSHR are more sensitive to suppression of BRS due to arousal elicited by stimulation of the amygdala. Furthermore, the amygdala is necessary for arousal-induced suppression of BRS in WKR and spSHR.

Amygdala

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

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

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

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

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

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