Effect of angiotensin II and 5-hydroxytryptamine on the vessels of the human foetal cotyledon

1 The actions of angiotensin II (AT II) and 5-hydroxytryptamine (5-HT) on the vessels of the human isolated, perfused, cotyledon were examined in vitro. 1 The cotyledonary vessels were shown to respond to both AT II and 5-HT over the range 10(-8) to (10(-4) M. 3 The preparation was found to be more responsive to AT II than 5-HT. 4 The findings confirm that the responsiveness of the cotyledonary vessels differs from the vessels of the umbilical cord, and that this behaviour does not depend upon the integrity of the endothelium associated with these vessels.     

Fetal endocrine responses to chronic placental embolization in the late-gestation ovine fetus

OBJECTIVE: The purpose of this study was to examine the effect of chronic fetal placental embolization on the fetal corticotropin, cortisol, and catecholamines concentrations and on myometrial contractility pattern. STUDY DESIGN: Fourteen fetal sheep were studied (seven embolized, seven controls) for 10 days between 0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were performed to decrease fetal arterial oxygen content by 30% to 35% of the preembolization value. Umbilical artery Doppler flow velocity waveforms were measured daily. RESULTS: Chronic fetal placental embolization produced progressive fetal hypoxemia (p < 0.001) with changes in umbilical artery Doppler flow velocity waveforms indicative of a 25% increase in placental vascular resistance (p < 0.01). In response to chronic fetal hypoxemia there was a progressive increase in baseline fetal plasma norepinephrine concentration (p < 0.001). There was a transient fourfold to fivefold increase in baseline fetal plasma cortisol levels concomitant with a significant decrease in baseline immunoreactive corticotropin between days 7 and 9 of embolization (both p < 0.05), with a return to control values by day 10. There was a 57% increase in myometrial contracture frequency in the embolized group when compared with controls (p = 0.001). CONCLUSIONS: During repetitive chronic placental damage that led to fetal hypoxemia, the fetal endocrine environment changed with time in a direction that would prevent the onset of premature activation of the hypothalamic-pituitary-adrenal axis and premature delivery.     

Effect of chronic alcohol consumption on responses of cerebral arterioles

Ventilator-associated pneumonia (VAP) due to multiresistant pathogens is associated with a high death rate. We analyzed the relationship between VAP due to Pseudomonas or Acinetobacter species and death by comparing the outcomes for patients colonized with these pathogens (bacterial counts of < 10(3) cfu/mL) with those for patients with pneumonia due to these pathogens (bacterial counts of > or = 10(3) cfu/mL). Samples were obtained systematically with a protected specimen brush when pneumonia was suspected. Clinical characteristics at admission to our intensive care unit and clinical features at the time of suspicion of VAP were not significantly different between colonized patients and those with VAP. Mortality rates were 29% among colonized patients and 73% among patients with VAP (P < .001). These results demonstrate a relationship between a high mortality rate and the development of pneumonia due to multiresistant, nonfermenting, gram-negative bacilli ( > or = 10(3) cfu/mL) in the lower airways of patients receiving ventilatory support.     

Effect of chronic exposure to cold on some responses to catecholamines

Eighty-one strans of Mycoplasma arginini were isolated from swabs and tissues cultured from a series of 555 cats. The majority of these strains (84%) were recovered from the oropharyngeal regions. M. arginini was experimentally inoculated into young kittens. No clinical disease was produced. However, there was rapid colonization in the inoculated sites.     

Effect of acute and chronic hypoxia on the structure of the neural elements of the brain

In rats subjected to the effect of 10 000 m "altitude" for 2 h, numerous nerve cells in different areas of the brain (cortex of both cerebral hemispheres, cerebellum, optic thalamus, hippocamp, pons varolii) had morphological features peculiar to a reversible and irreversible dystrophic process. Similar changes were not observed in the brain of rats subjected to the effect of 9000 m "altitude" for one hour. Nerve cells in all brain areas are rich in substance of Nissl. In the rats adapted to hypoxia, as in the rats from the first experiment, the nerve cells are enlarged in their dimentions, the substnace of Nissl in their cytoplasm is seem increased. The destructive changes in neurons are scarce. Many neurons of the cortex have signs pointing to an increased activity of nucleus and nucleolus. Satallitosis and quantitative augmentation of glial cells is noted.     

Effect of meperidine on occlusion pressure responses to hypercapnia and hypoxia with and without external inspiratory resistance

In 5 normal subjects we measured ventilation and P0.1, the pressure generated by the first 0.1 sec of inspiratory effort against a closed airway, in response to hypercapnia and hypoxia with and without added inspiratory resistance before and after oral meperidine (1.1 to 1.3 mg per kg). CO2 responses were studied in the steady state, whereas progressive hypoxia was used to elicit hypoxic responses. In general, resistance decreased ventilatory responses to hypercapnia but increased P0.1 responses to both hypoxia and hypercapnia. Meperidine depressed both ventilatory and P0.1 responses, more so in hypoxia than in hypercapnia. The combination of resistance and merperidine was additive in depressing responses to hypercapnia but in hypoxia produced little more depression than did meperidine alone. In both hypercapnia and hypoxia, meperidine decreased the augmentation of P0.1 that was associated with increased resistance. Normal subjects responded to acute increases of inspiratory resistance by increasing inspiratory motor output; this increase was distinctly blunted by meperidine.     

Effect of 764-3 and ligustrazine on collagen content of extrapulmonary arteries during chronic hypoxia

OBJECTIVE: Effect of two antifibrotic Chinese drugs, 764-3 and ligustrazine, on collagen content in chronic hypoxic pulmonary hypertensive extrapulmonary arterial wall were examined. METHODS: Since collagen contains more than 10% hydroxyproline by weight and in other proteins there are almost no hydroxyproline, collagen content was expressed as micrograms of hydroxyproline. Hydroxyproline was determined by calorimetric method after oxidized by chloramine T. RESULTS: Both 764-3 and ligustrazine significantly inhibited the increase of pulmonary arterial pressure and elevation of hydroxyproline content in extrapulmonary arterial wall during chronic hypoxia. CONCLUSIONS: 764-3 and ligustrazine may be two hopeful therapeutic drugs for chronic hypoxic pulmonary hypertension.     

Influence of applied tension and nitric oxide on responses to endothelins in rat pulmonary resistance arteries: effect of chronic hypoxia

1. The effect of basal tension (transmural tensions 235 +/- 29 mg wt (low tension: equivalent to approximately 16 mmHg) and 305 +/- 34 mg wt (high tension: equivalent to 35 mmHg)) on rat pulmonary resistance artery responses to endothelin-1 (ET-1) and the selective ET(B)-receptor agonist sarafotoxin S6c (S6c) were studied. The effects of nitric oxide synthase inhibition with N(omega)-nitro-L-arginine methylester (L-NAME, 100 microM) on ET receptor-induced responses, as well as vasodilator responses to acetylcholine (ACh) and S6c, were also investigated. Changes with development of pulmonary hypertension, induced by two weeks of chronic hypoxia, were determined. 2. Control rat preparations showed greatest sensitivity for ET-1 when put under low tension (pEC50: 8.1 +/- 0.1) compared with at the higher tension (pEC50: 7.7 +/- 0.1) and there were significant increases in maximum contractile responses to S6c (approximately 80%) and noradrenaline (approximately 60%) when put under high tension. 3. In control pulmonary resistance arteries, both ET-1 and S6c produced potent vasoconstrictor responses. S6c was 12 fold more potent than ET-1 in vessels set at low tension (S6c pEC50: 9.2 +/- 0.1) and 200 fold more potent than ET-1 when the vessels were set at high tension (S6c pEC50: 9.0 +/- 0.1). Chronic hypoxia did not change the potencies of ET-1 and S6c but did significantly increase the maximum contractile response to ET-1 by 60% (at low tension) and 130% (at high tension). 4. In control rat vessels, L-NAME itself caused small increases in vascular tone (5-8 mg wt tension) in 33-56% of vessels. In the chronic hypoxic rats, in vessels set at high tension, L-NAME-induced tone was evident in 88% of vessels and had increased to 26.9 +/- 6.6 mg wt tension. Vasodilatation to sodium nitroprusside, in non-preconstricted vessels, was small in control rat vessels (2-6 mg wt tension) but increased significantly to 22.5 +/- 8.0 mg wt tension in chronic hypoxic vessels set at the higher tensions. Together, these results indicate an increase in endogenous tone in the vessels from the chronic hypoxic rats which is normally attenuated by nitric oxide production. 5. L-NAME increased the sensitivity to S6c 10 fold (low tension) and 6 fold (high tension) only in chronic hypoxic rat pulmonary resistance arteries. It had no effect on responses to ET-1 in any vessel studied. 6. Vasodilatation of pre-contracted vessels by ACh was markedly greater in the pulmonary resistance arteries from the chronic hypoxic rats (pIC50: 7.12 +/- 0.19, maximum: 72.1 +/- 0.2.0%) compared to their age-matched controls (pIC50: 5.77 +/- 0.15, maximum: 28.2 +/- 2.0%). There was also a 2.5 fold increase in maximum vasodilatation induced by ACh. 7. These results demonstrate that control rat preparations showed greatest sensitivity for ET-1 when set at the lower tension, equivalent to the pressure expected in vivo (approximately 16 mmHg). Pulmonary hypertension due to chronic hypoxia potentiated the maximum response to ET-1. Pulmonary resistance arteries from control animals exhibited little endogenous tone, but exposure to chronic hypoxia increased endogenous inherent tone which is normally attenuated by nitric oxide. Endogenous nitric oxide production may increase in pulmonary resistance arteries from chronic hypoxic rats and attenuate contractile responses to ET(B2) receptor stimulation. Relaxation to ACh was increased in pulmonary resistance arteries from chronic hypoxic rats.     

Immunohistochemical distribution of oestrogen receptor and luteinizing hormone B subunit in the ovine pituitary gland during foetal development

The presence of oestrogen receptor in the developing hypothalamo-hypophyseal system is an essential prerequisite for the development of sex-steroid feedback on gonadotrophin secretion. We have used dual immunocytochemistry to examine the ontogeny and regional distribution of oestrogen receptor and LHbeta subunit in the ovine pituitary gland during foetal development. At day 65 gestation (term= 145 days) oestrogen receptor and LH/ immunopositive cells are found in a small region at the base of the anterior pituitary gland, and also in a band immediately adjacent to the neurointermediate lobe. By day 100 gestation there was a significant increase in the number of immunopositive LHbeta cells accounting for around 12% of the total cell population, and these were widely distributed throughout the anterior pituitary gland. There was also a significant increase in the proportion of gonadotrophs which contain oestrogen receptor compared with day 65. By day 130 gestation the percentage of LH containing cells had declined to around 7% of the total population, but the proportion which also contained oestrogen receptor remained the same. There were no differences in the numbers or distribution of cells containing LH or oestrogen receptors between male and female foetuses, at any age. These data describing a parallel change in the number of oestrogen receptors and LHbeta containing cells in the pituitary gland throughout gestation suggest that the development of pituitary sex-steroid feedback is not solely dependent on changes in the numbers of oestrogen receptor containing cells alone.     

Effect of chronic treatments with tandospirone and imipramine on serotonin-mediated behavioral responses and monoamine receptors

The effects of acute and chronic treatment of rats with the tricyclic antidepressant imipramine, the 5-HT1A receptor partial agonist tandospirone, or its metabolite 1-PP were compared on behavioral responses produced by the activation of 5-HT receptors and on brain monoamine receptors. The behaviors examined were the 5-HT behavioral syndrome elicited by the 5-HT1A receptor agonist 8-OH-DPAT and the head shake response produced by the 5-HT2 receptor agonist DOB. Drug treatments were administered either by subcutaneous infusion from implanted minipumps or by repeated injection and the effects of chronic drug treatment were assessed when the drug was present and absent at the time of testing. The infusion of tandospirone blocked elicitation of the 5-HT behavioral syndrome when tested after 1 or 14 days of drug treatment (drug present) and 24 hr after the drug was withdrawn (drug absent). When administered by injection, tandospirone blocked the production of the 5-HT syndrome 1 hr (drug present), but not 24 hr (drug absent), following either 1 day or 14 days of drug treatment. Chronic infusion of imipramine did not alter the 5-HT syndrome. Chronic, but not acute, injections of imipramine blocked the 5-HT syndrome when tested 1 hr but not 24 hr, after the final injection. Treatment with 1-PP did not alter the 5-HT syndrome. The head shake response was attenuated by acute and chronic injection of tandospirone either 1 or 24 hr after treatment, although chronic infusion of tandospirone did not alter this behavior. Head shaking was attenuated by the infusion and injection of imipramine after acute treatment, chronic treatment, or following drug withdrawal. Chronic injection of 1-PP also inhibited the head shake response 24 hr after injection, although 1-PP was ineffective at all other times and when given by infusion. The density of hippocampal 5-HT1A receptors was unaltered by the chronic drug treatments. 5-HT2 receptor density in frontal cortex was reduced by the chronic infusion of either tandospirone, imipramine, and 1-PP, but only by chronic injections of imipramine. The density of cortical beta-adrenergic receptors was reduced following chronic imipramine injections or infusion. The results suggest that both tandospirone and imipramine may regulate 5-HT-mediated responses and 5-HT2 receptor density, which may contribute to their efficacy as antidepressants, although their effects were dependent upon the method of administration and may involve different neuropharmacological mechanisms.     

Effect of gamma radiation on the foetal haemopoietic system in the mouse

In this study, the wall motion of the common carotid artery was characterized by measuring wall-motion velocity (Wv) with tissue Doppler imaging (TDI) in 78 male and female subjects (16-75 y) with no history of cardiovascular disease. The near and far arterial wall showed essentially different Wv patterns. To assess the vascular systolic distension, the Wv of the near and far arterial walls were measured and a Wv index was calculated by subtracting the far Wv from the near Wv. Aging was associated with a 2.0-2.5-fold decrease of peak Wv index. Corrected for carotid diameter and blood pressure, the peak Wv index and mean systolic acceleration to the peak Wv correlated highly with arterial distensibility (r = 0.81 resp. r = 0.75) and compliance (r = 0.73 resp. r = 0.68). This study demonstrates the feasibility of TDI in the characterization of wall motion patterns and in the assessment of common carotid artery stiffness.     

Myocyte adaptation to chronic hypoxia and development of tolerance to subsequent acute severe hypoxia

Studies in animal models and humans suggest that myocardium may adapt to chronic or intermittent prolonged episodes of reduced coronary perfusion. Stable maintenance of partial flow reduction is difficult to achieve in experimental models; thus, in vitro cellular models may be useful for establishing the mechanisms of adaptation. Since moderate hypoxia is likely to be an important component of the low-flow state, isolated adult rat cardiac myocytes were exposed to 1% O2 for 48 hours to study chronic hypoxic adaptation. Hypoxic culture did not reduce cell viability relative to normoxic controls but did enhance glucose utilization and lactate production, which is consistent with an anaerobic pattern of metabolism. Lactate production remained transiently increased after restoration of normal O2 tension. Myocyte contractility was reduced (video-edge analysis), as was the amplitude of the intracellular Ca2+ transient (indo 1 fluorescence) in hypoxic cells. Relaxation was slowed and was accompanied by a slowed decay of the Ca2+ transient. These changes were not due to alterations in the action potential. Tolerance to subsequent acute severe hypoxia occurred in cells cultured in 1% O2 and was manifested as a delay in the time to full ATP-depletion rigor contracture during severe hypoxia and enhanced morphological recovery of myocytes at reoxygenation. The latter was still seen after normalization of the data for the prolonged time to rigor, suggesting a multifactorial basis for tolerance. An intervening period of normoxic exposure before subsequent acute severe hypoxia did not result in loss of tolerance but rather increased the delay to subsequent ATP depletion rigor. Cellular glycogen was preserved during chronic hypoxic exposure and increased after the restoration of normal O2 tension. As mitochondrial cytochromes should be fully oxygenated at levels well below 1% O2, hypoxic adaptation may be mediated by a low-affinity O2-sensing process. Thus, adaptations that occur during prolonged periods of moderate hypoxia are proposed to poise the myocyte in a better position to tolerate impending episodes of severe O2 deprivation.     

Morphometric study of the placental vessels and its correlation with umbilical artery Doppler flow

OBJECTIVE: To determine the changes in the vessel-wall thickness and the radius of the lumen in tertiary-stem villi of the placenta with advancing gestational duration and their relationship to umbilical artery Doppler flow studies. METHODS: Placentas from 63 miscarriages and preterm and term deliveries (between 19 and 40 weeks) were used for morphometric study of the tertiary-stem villi vessels. Each woman had undergone Doppler flow study of the umbilical artery. The resistance index (RI) was determined from the Doppler flow velocity waveform. Placental paraffin sections of 4-micron thickness were stained with hematoxylin and eosin and with periodic acid-Schiff reagents. The tertiary-stem villi and their vessels were examined microscopically and assessed morphometrically using a personal computer with math co-processor and a touch-sensitive screen overlying a video monitor. The monitor received microscopic images from a video camera that was mounted on a microscope. We determined vessel-wall thickness by tracing the outer and inner circumferences of digitized vessel-wall images. RESULTS: Wall thickness, but not lumen size, of the tertiary-stem villi vessels decreased significantly overall at a rate of 0.63micron/week (P < .001). The rate of decrease was 0.64micron/week (P < .001) during the second trimester and 0.50micron/week (P < .001) during the third trimester. There was a significant correlation between the decrease in thickness and in RI (r = 0.83 [P < .001], r = 0.78 [P < .001] in the second and third trimesters, respectively). Resistance indices were all within normal limits. CONCLUSIONS: Placental tertiary-stem villi vessel-wall thickness decreases with advancing gestational age. There is a correlation between the changes in RI of the umbilical artery Doppler flow and the changes in mean wall thickness of the placental vessels.     

Effect of fibrinogen degradation products on the rat blood vessels

Effect of fibrinogen degradation products on the rat blood vessels. Acta Physiol. Pol. 1977, 28 (2): 153--159. It was found that fibrinogen degradation products (FDP) exert a slight hypotensive effect and increase the flow of Tyrode's solution through isolated hindpaw of rat. The investigated peptides failed to change significantly the action of noradrenaline and had an additive effect with isoprenaline. Propranolol reduced the effects of FDP and isoprenaline. It is suggested that the described effects may be due to stimulation of the vascular beta-adrenergic receptors by FDP.     

A transient effect of estrogen on calcium currents and electrophysiological responses to gonadotropin-releasing hormone in ovine gonadotropes

Episodic release of luteinizing hormone (LH) by the pituitary gland is controlled by hypothalamic gonadotropin-releasing hormone (GnRH). In the period leading up to the preovulatory surge of LH, estrogen increases the number of pituitary receptors for GnRH and sensitises the gonadotropes to GnRH. The postreceptor events that are responsible for the increase in responsiveness to GnRH are not clearly delineated, but LH release is known to be Ca2+ dependent. The present study addressed the question as to whether or not estrogen may act to modify voltage-dependent Ca2+ entry in normal gonadotropes. Primary cultures enriched in gonadotropes or somatotropes were produced from anestrous female sheep. Conventional whole-cell patch-clamp recording was used to measure inward membrane current in the absence of GnRH treatment, with and without 10 nM estradiol-17beta (E2) treatment for 0 to 36 h. Nystatin-perforated whole-cell patch-clamp recording was used to record membrane voltage responses to GnRH. Ca2+ current density (ICa, pA/pF) began to increase after 2 h exposure to E2, and reached peak values of about 200% of control by 16-20 h (p < 0.005), then declined. If E2 was withdrawn at 24 h, ICa returned towards control values by 36 h. If E2 treatment was continued beyond 24 h, however, ICa fell to about 75% of control by 36 h (p < 0.005). Actinomycin D prevented the enhancement of ICa. E2 was without effect on Na+ current density in gonadotropes, or on ICa in somatotropes. The proportion of ICa carried by L-type and N-type channels in gondadotropes was not changed by E2. Ovine gonadotropes respond to GnRH with membrane potential fluctuations driven by periodic activation of Ca2+-dependent K+ channels, and synchronised action potential generation. This response was found to be sensitive to E2. Responses were categorised according to the pattern of activity evoked by 10 nM GnRH. Without E2 treatment, 11/14 cells responded with oscillations and 3/14 cells responded with spiking (hyperpolarizations following single action potentials). After 20 h 10 nM E2, just 1/14 cells responded with hyperpolarizing oscillations while 13/14 cells showed spiking activity. The predominance of the spiking pattern in E2-treated cells is consistent with the increased Ca2+ flux, and with enhanced LH release. We conclude that E2 has a transient effect on gonadotropes to enhance voltage-gated Ca2+ channel function. The time-course and biphasic nature of the influence of E2 on ICa may be physiologically appropriate to the preovulatory LH surge. Enhanced Ca2+ influx may participate in increased Ca2+-dependent hormone release, while the delayed inhibitory action of E2 on ICa may serve to limit the duration of the surge.     

An ovine model of acute myocardial infarction and chronic left ventricular dysfunction

In order to develop and validate an ovine model of myocardial infarction with subsequent impairement of left ventricular function, 15 instrumented sheep underwent selective microembolization of the left coronary arteries with 0.5 mL 90 microns polystyrene beads. Hemodynamics and plasma hormones were measured preembolization (baseline) and then at hours 2, 4, 6, and 12 and days 1, 2, 3, 5 and 7 postembolization. Of the 15 sheep studied, 2 (13%) died on the day of embolization from arrhythmias. In the remaining sheep, left ventricular systolic pressure and stroke work (both P < 0.001) were reduced promptly and remained below basal levels. Mean arterial pressure (P < 0.001) increased initially, then decreased to below basal levels by hour 6. Heart rate (P < 0.001) and left atrial pressure (P < 0.05) were increased while cardiac output was decreased (P < 0.05). Left ventricular ejection fraction at day 7 was reduced (38.8 +/- 3.5 vs 46.0 +/- 3.9% preembolization; P < 0.05). The cardiac enzymes creatine kinase (P < 0.001) and troponin-T (P < 0.001) were increased following microembolization and returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain natriuretic peptides (both P < 0.001) and plasma renin activity (P < 0.005) were all increased following embolization. This ovine model mimics the hemodynamic and neurohumoral features of acute myocardial infarction, resulting in left ventricular dysfunction, and should prove suitable for the study of interventions in a number of these conditions.     

Effect of vagal denervation of the cerebral vessels on cerebellar neurons

Under study were the neurons of the cerebellum cortex of adult cats after a right-side transection of the vagus nerve cranially to its ganglion. The neuron structure was studied in frontal 10-20 mu thick paraffin sections stained with thionine after Nissl 1, 2, 10, 20 days and 1, 2, 3 months after operation. Pathomorphological alterations of neurons were revealed in all layers of the cerebellum cortex. The alterations were of bilateral character, but were more pronounced in the operation side.