Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhaled nitric oxide (NO) is an important new therapeutic agent used to treat pulmonary arterial hypertension in a variety of disease states. However, the effects of NO on cells in the lung are uncertain. Previously, we have shown that NO gas depresses neutrophil oxidative cell function and increases neutrophil cell death. The purpose of this in vitro study was to determine the mechanism of neutrophil death. We hypothesized that NO hastened cell death by inducing apoptosis. To mimic the clinical environment of patients with respiratory failure, we also studied the effects of hyperoxia on neutrophil cell viability and apoptosis. Isolated human neutrophils were exposed to 80% O2 (O2), NO at 20 ppm in room air (NO/RA), 20 ppm NO blended with 80% O2 (NO/O2), or RA alone (control) for 2 to 24 h. Experiments were repeated with NO concentrations of 5 and 50 ppm and with 20 ppm in the presence of superoxide dismutase (SOD). Neutrophils were also incubated in the absence or presence of neutrophil stimulant fMLP (10 nM). Neutrophil cell viability was measured by fluorescence viability/cytotoxicity assay. Neutrophil apoptosis was assessed by cell death detection ELISA for histone-associated DNA fragments, TdT transferase-mediated fluorescence-labeled dUTP nick end labeling (TUNEL) assay, and DNA fragmentation gel electrophoresis. NO/O2-exposed neutrophils showed decreased viability at 2 h (31.7 +/- 3.7%, mean % viability +/- SD) compared with control (94.7 +/- 4.7%), O2 (75.6 +/- 9.3%), and NO/RA (62.8 +/- 14.9%; P < 0.05 by ANOVA; n = 9). Although control neutrophils demonstrated marked apoptosis at 24 h, there was no significant apoptosis at 2, 4, or 6 h (P < 0.001 by Kruskal-Wallis, n = 20) as assessed by ELISA and TUNEL assays. When compared with RA controls at 2 h, neutrophils exposed to NO/O2 showed significantly more apoptosis (292% of control, range: 106 to 2,488%, P < 0.001 by ANOVA and Kruskal-Wallis) but not with exposure to NO/RA or O2 alone. These findings were confirmed by TUNEL assay (n = 4, P < 0.05). NO/ RA and NO/O2-exposed neutrophils demonstrated both evidence of necrosis and enhanced DNA fragmentation at 2 h by gel electrophoresis (n = 2). Fifty parts per million NO produced similar findings, but exposure to 5 ppm NO did not induce significant DNA fragmentation. Coincubation with SOD inhibited NO/ O2-associated apoptosis, suggesting peroxynitrite contributed to cell death. Stimulation with fMLP did not alter apoptosis induced in neutrophils exposed to NO/RA or NO/O2. We conclude that exogenous NO gas, at clinically relevant concentrations under hyperoxic conditions, induces cell death in neutrophils in part by enhancing DNA fragmentation.
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PMID:Exogenous nitric oxide enhances neutrophil cell death and DNA fragmentation. 949 Jun 60

The objective of our study was: (1) to compare the influence of moderate exercise on circulatory after-response in mildly hypertensive (n = 8) and normotensive male subjects (n = 9); (2) to examine the circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors at rest and during postexercise period in both groups. Hypertensive men (HTS) with a systolic blood pressure (SBP) 148 +/- 5 mm Hg, diastolic blood pressure (DBP) 92.4 +/- 4 mm Hg; and normotensive men (NTS), with a SBP 126 +/- 3 mm Hg, DBP 75.6 +/- 1.3 mm Hg, were submitted to 20-min of moderate exercise on a cycloergometer (up to the level of 55% of each subject's resting heart rate reserve). Finger arterial BP was recorded continuously with Finapres, impedance reography was used for recording stroke volume, cardiac output and arm blood flow. In HTS a significant decrease in SBP by 14.5 +/- 3.4 mm Hg, DBP by 8.9 +/- 1.9 mm Hg, total peripheral resistance (TPR) by 0.45 +/- 0.05 TPR u. (33.7 +/- 2.7%), and in arm vascular resistance (AVR) by 11.0 +/- 2.7 PRU u. (35.6 +/- 7%), was observed over a 60-min postexercise period. NTS exhibited insignificant changes in SBP, DBP, AVR except a significant decrease in TPR limited only to 20-min postexercise period. Hyperoxia decreased SBP, DBP and TPR in HTS. This effect was significantly attenuated during the postexercise period. Long-lasting antihypertensive effect of a single dynamic exercise in HTS suggests that moderate exercise may be applied as an effective physiological procedure to reduce elevated arterial BP in mild hypertension. We suggest also that the attenuation of the sympathoexcitatory arterial chemoreceptor reflex may contribute to a postexercise decrease in arterial BP and in TPR in mildly hypertensive subjects.
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PMID:Postexercise decrease in arterial blood pressure, total peripheral resistance and in circulatory responses to brief hyperoxia in subjects with mild essential hypertension. 988 9

Vascular endothelial cell apoptosis has previously been shown to play a role in the pathogenesis of hypertension-induced vessel deletion and damage. In the present in vitro study we analyse several possible relevant causative factors of vascular endothelial cell apoptosis, namely, serum deprivation and nutrient depletion, oxidative stress in the forms of hypoxia, hyperoxia or free radical damage, and altered levels of transforming growth factor-beta1 (TGF-beta1) protein. An established cell line, bovine aortic endothelial cells (BAEC), was maintained in complete growth medium (RPMI-1640 plus 15% fetal calf serum and antibiotics, abbreviated as RPMI) in 25cm2 flasks or in 12-well plates on glass coverslips. Confluent but actively-growing cultures were treated with either hypoxia (PO2 of RPMI = 50mmHg), serum-free media (SFM), SFM plus hypoxia, hyperoxia (PO2 of RPMI = 450mmHg), hydrogen peroxide (H2O2, 1mM) in SFM, or TGF-beta1 protein (10ng/mL) in SFM. Appropriate control cultures were used. BAEC were collected 48h or 72h after all treatments except for TGF-beta1 and H2O2 treatments that were collected at 16-18h. Cell death was assessed using morphological characteristics or in situ end labeling (ISEL), cell proliferation assessed using proliferating cell nuclear antigen (PCNA), and TGF-beta1 expression assessed using transcript levels or immunohistochemistry. All treatments significantly increased levels of apoptosis over control cultures (P<0.05), and decreased levels of cell proliferation. Treatment with TGF-beta1 protein or SFM plus hypoxia induced greatest levels of apoptosis. TGF-beta1 protein and transcript levels were decreased in treated cultures, results suggesting that a paracrine source of TGF-beta1 protein would be needed as a cause of endothelial cell apoptosis in viva. Future therapies against inappropriate vessel deletion in disease states may use the known gene-driven nature of apoptosis to modify this sort of cell death in endothelial cells.
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PMID:Apoptosis in vascular endothelial cells caused by serum deprivation, oxidative stress and transforming growth factor-beta. 1059 59

The mechanism of pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is unknown. Many investigators point to the high sympathetic nervous system activity (SNS) observed in OSA patients. However, there is no clear explanation as to the mechanism for the development of SNS hyperactivity in these patients. A common feature of patients with OSA is repetitive bouts of transient hypoxemia during sleep. Repetitive transient hypoxemia in rats has resulted in hypertension. In OSA patients, resolution of nocturnal hypoxemia with CPAP has corrected nocturnal and diurnal hypertension. Also, exposure to hyperoxia reduces blood pressure and sympathetic activity in OSA patients, but not in normals. These data suggest a significant role of peripheral chemoreceptors in the regulation of vascular tone. We hypothesize that peripheral chemoreceptors significantly contribute to the pathogenesis of hypertension in patients with OSA and that this is associated with chemoreceptor hyperactivity. This implies that correcting the intermittent nocturnal hypoxemia alone may prevent the cardiovascular morbidity associated with obstructive sleep apnea.
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PMID:Obstructive sleep apnea and hypertension: are peripheral chemoreceptors involved? 1113 49

The major function of the erythrocyte is to transport oxygen from the lungs to the other tissues, a function ensured by the glycoprotein hormone erythropoietin which couples red cell production to long term tissue oxygen requirements. Tissue hypoxia is the only physiological mechanism for increasing erythropoietin production but there are a variety of mechanisms for its down regulation including hyperoxia, increased catabolism by an expanded erythroid progenitor cell pool, blood hyperviscosity independently of its oxygen content, renal disease and the cytokines produced in inflammatory, infectious and neoplastic disorders. Erythropoietin lack results in severe and often transfusion-dependent anemia but if bone marrow function is otherwise normal, recombinant human erythropoietin therapy can restore the red cell mass and alleviate the transfusion need. However, elevation of the red cell mass by recombinant human erythropoietin is associated with a reduction in plasma volume and in some patients, hypertension is induced. Elevation of the red cell mass is also associated with a reduction in cerebral blood flow. When used to gradually elevate the hematocrit to 36% in anemic patients, recombinant human erythropoietin therapy is usually uneventful. However, when the normal hematocrit level is exceeded, the risk for thrombotic events increases since blood viscosity varies exponentially with the hematocrit. Increasing the hematocrit by autologous blood transfusions can enhance athletic performance in fit individuals and recombinant human erythropoietin administration is an obvious surrogate for autologous blood transfusions. However, paradoxically, its effects are the opposite of those of endurance training, namely a change in red cell mass without an increase in the total blood volume. Thus, the use of recombinant human erythropoietin as a performance-enhancing agent is dangerous, particularly in the less fit athlete, and probably of little benefit in the highly conditioned one. Differences in the carbohydrate content of native and recombinant human erythropoietin are identifiable by isoelectric focusing, providing a direct means for detecting erythropoietin abuse using urine specimens; a panel of surrogate blood markers of enhanced erythropoiesis such as soluble transferrin receptors, serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an indirect means for this purpose. Timing of surveillance is, of course, critical due to biological limitations on the physical presence of the hormone. However, education about its dangers may prove to be the most valuable solution to abuse of recombinant human erythropoietin for competitive advantage.
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PMID:Erythropoietin use and abuse: When physiology and pharmacology collide. 1195 Jan 39

The purpose of the current study was to characterize the response of the recurrent laryngeal nerve (RLN) to pulmonary C-fiber activation. Male rats of Wistar strain were anesthetized by urethane (1.2 g/kg, i.p.). Tracheostomy was performed. Catheter was inserted into the femoral artery and vein. Additional catheter was placed near the entrance of the right atrium via the right jugular vein. The animal was then paralyzed with gallamine triethiodide, ventilated and maintained at normocapnia in hyperoxia. Activities of the phrenic (PNA) and recurrent laryngeal nerves (RLNA) were monitored simultaneously. Two experimental protocols were completed. In the first experiment, various doses of capsaicin were delivered into the right atrium to activate pulmonary C-fibers with vagal intact. Low dose of capsaicin (1.25 microg/kg) produced apnea, a decrease in amplitude of PNA, an enhancement of RLNA during apnea and recovery from apnea, hypotension, and bradycardia. High dose of capsaicin (5 and 20 microg/kg) evoked the same tendency of response for both nerves and biphasic changes in blood pressure. Dose dependency was only seen in the period of apnea but not observable in nerve amplitudes. After bilateral vagotomy, low dose of capsaicin produced an increase in PNA without apnea, no significant change in RLNA, and hypertension. These results suggest that activation of vagal and nonvagal C-fibers could produce different reflex effects on cardiopulmonary functions. The reflex responses evoked by these two types of afferents might play defensive and protective roles in the airways and lungs.
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PMID:Pulmonary C-fiber activation enhances respiratory-related activities of the recurrent laryngeal nerve in rats. 1281 5

Heme oxygenases catalyze the rate-limiting step in heme degradation, resulting in the formation of carbon monoxide, iron and biliverdin that is subsequently reduced to bilirubin by biliverdin reductase. The products of this enzymatic reaction have important biological effects, including antioxidant, anti-inflammatory and cytoprotective functions. Three isoforms of heme oxygenase (HO) have been described: two constitutively expressed isoforms, HO-2 and HO-3, and an inducible isoform, HO-1 that is increased as an adaptive response to several injurious stimuli including heme, hyperoxia, hypoxia, endotoxin and heavy metals. Induction of HO-1 has been implicated in numerous clinically relevant disease states including transplant rejection, hypertension, atherosclerosis, lung injury, endotoxic shock and others. This review will focus on the protective functions of HO-1.
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PMID:Heme oxygenase-1 as a protective gene. 1549 91

Heart transplantation initially normalizes sympathetic hyperactivity directed at the muscle circulation. However, sympathetic activity increases with time after transplantation and the exact mechanisms responsible for sympathetic control in heart transplant recipients remain unclear. We examined the effects of peripheral chemoreflex deactivation caused by breathing 100% oxygen on muscle sympathetic nerve activity (expressed as number of burst per minute and mean burst amplitude), heart rate, and mean blood pressure in 13 heart transplant recipients, 13 patients with essential hypertension, and 10 controls. Heart transplant recipients disclosed the highest sympathetic activity, whereas it did not differ between controls and patients with essential hypertension (51+/-16 versus 37+/-14 versus 39+/-12 burst/min, respectively; P<0.05). Breathing 100% oxygen, in comparison with 21% oxygen, reduced sympathetic activity (-4+/-4 versus -1+/-2 burst/min, P<0.01; 85+/-9 versus 101+/-8% of amplitude at baseline, P<0.001) and mean blood pressure (-4+/-5 versus +3+/-6 mm Hg; P<0.05) in heart transplant recipients, decreased sympathetic activity (-4+/-4 versus 0+/-3 burst/min, P<0.05; 90+/-16 versus 101+/-9% of amplitude at baseline, P<0.05) in patients with essential hypertension, but did not reduce sympathetic activity (2+/-4 versus 3+/-3 burst/min, P=NS; 95+/-11 versus 95+/-13% of amplitude at baseline, P=NS) in control subjects. The sympathetic response to hyperoxia was more marked in heart transplant recipients than in controls (85+/-9 versus 95+/-11% of baseline amplitude; P<0.05). The decrease in sympathetic activity was most evident in patients with the longest time after heart transplantation (r=-0.75, P<0.01). In conclusion, tonic chemoreflex activation increases resting muscle sympathetic nerve activity and favors blood pressure elevation after heart transplantation.
Hypertension 2005 May
PMID:Effects of peripheral chemoreceptors deactivation on sympathetic activity in heart transplant recipients. 1579 65

The aim of our study was to check the responsiveness the chemoreceptor reflex in 28 young mildly hypertensive men (HTS), aged 18-32 years and 25 normotensive male subjects (NTS) aged 19-32 years, before and after 3-months dynamic exercise training. We tested the hypothesis that dynamic training reduces arterial chemoreceptor drive in mild hypertension. Circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors induced by 70% oxygen breathing was measured before and after training. Arterial blood pressure (BP) was recorded continuously by Finapres method, stroke volume and arm blood flow were registered by impedance reography, heart rate by ECG. Both groups were submitted to moderate 3-months dynamic exercise training. Before training the hyperoxic breathing caused in HTS a significant decrease in systolic BP by 6+/-1 mmHg p<0.01, in diastolic BP by 2+/-0.6 mmHg p<0.01, and in total peripheral vascular resistance (TPR) by 0.24+/-0.04 TPRU (p<0.01). After training hyperoxia augmented systolic BP by 2.64+/-1.9 mmHg (NS), diastolic BP by 2+/-1 mmHg p<0.05, and TPR by 0.043+/-0.05 TPRU (ANOVA). In NTS before training brief hyperoxia produced insignificant change in BP and TPR. In NTS after training hyperoxia increased systolic BP by 4.2 mm Hg+/-1.23 p<0.01 and diastolic BP by 3.1+/-0.6 mmHg p<0.01 respectively and TPR by 0.053+/-0.02 TPRU. Our results confirm earlier finding on the enhanced arterial chemoreceptor reflex drive in mild human hypertension. We conclude that normalizing arterial blood pressure in subjects with mild hypertension which occurred after 3-months dynamical exercise training is due to attenuation of the sympathoexcitatory chemoreceptor reflex drive by exercise training. The mechanism of this effect requires further study.
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PMID:Moderate exercise training reduces arterial chemoreceptor reflex drive in mild hypertension. 1724 41

Cardiopulmonary resuscitation does not end with restoration of spontaneous circulation; rather, it must be continued with the application of all the measures that allow organ function to be maintained. The initial goal of hemodynamic treatment is to achieve normal blood pressure for the patient's age by means of fluids and/or vasoactive drugs. The aim of respiratory treatment is to normalize ventilation and oxygenation without causing further lung injury, avoiding hyperoxia and hyperventilation as well as hypoxia and hypercapnia. Neurological stabilization aims to reduce secondary brain damage, by avoiding hypertension and hypotension, maintaining normal ventilation and oxygenation, and treating hyperglycemia, agitation and seizures. Although no specific studies in children are available, data from adults have shown that early moderate hypothermia attenuates brain damage secondary to cardiorespiratory arrest, without increasing complications. After the arrest, the need for analgesia and/or sedation must be considered. The process of transportation to the pediatric intensive care unit (PICU) requires the following steps: stabilizing the patient, checking for and stabilizing fractures and external wounds, ensuring a stable airway and intravenous lines, assessing the need for nasogastric and bladder tubes, taking blood samples for analyses, contacting the PICU and informing the staff about the child's condition, choosing the optimal vehicle for transportation according to the child's condition and the distance, checking pediatric equipment and medications, selecting experienced staff and, finally, maintaining close surveillance and monitoring during transportation.
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PMID:[Post-resuscitation stabilization and transportation]. 1734 Jul 87


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