Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats injected intravenously with oleic acid developed pulmonary edema leading to hypoxia and hypercarbia. These changes were accompanied by an increase in immunoreactive endothelin (ir-ET) in plasma as early as 15 min after injection. At 45 min after injection plasma levels peaked at 114 +/- 19 pg/ml plasma (n = 8) and reached basal levels again after 240 min. In contrast, much larger amounts of ir-ET were found in the bronchoalveolar lavage fluid, with a peak at 120 min (2878 +/- 258 pg/lung, n = 7) preceding the maximum hypoxia observed at 180 min. In both plasma and bronchoalveolar lavage fluid samples ir-ET was characterized by reverse-phase HPLC as a mixture consisting mainly of ET-1 and smaller amounts of big ET-1, ET-2 and ET-3. In light of the biological effects of ET, the data suggest that these peptides might be of pathophysiological significance in this model of adult respiratory distress syndrome.
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PMID:Release of endothelin in the oleic acid-induced respiratory distress syndrome in rats. 161 74

The effects of endothelin 1 on the internal maxillary artery blood flow, measured as an index of cerebral blood flow, were examined in six unanesthetized goats under control conditions, hypercapnia induced by inhalation of 10% CO2 in air, hypertension by intravenous infusion of norepinephrine, and hypotension by intravenous injection of diazoxide. Under control, administration of endothelin (0.01-0.3 nmol) into the internal maxillary artery produced dose-dependent sustained decreases in cerebral blood flow and increases in cerebrovascular resistance; higher doses (0.1 and 0.3 nmol) also caused hypertension and bradycardia. During hypercapnia or hypertension, endothelin did not significantly affect cerebral blood flow, and only higher doses (0.1 and/or 0.3 nmol) increased cerebrovascular resistance, but this was lower than under control. However, under hypotension endothelin evoked a higher reduction in cerebral blood flow and increment in cerebrovascular resistance, and systemic effects were also more marked than under control. Therefore endothelin is a potent cerebral vasoconstrictor, and this effect is very attenuated during hypercapnia and hypertension but is increased under hypotension.
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PMID:Endothelin action on cerebral circulation in unanesthetized goats. 188 47

1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P < 0.01) and arterial CO2 partial pressure (PaCO2) significantly increased from 4.64 +/- 0.56 kPa to 8.15 +/- 0.99 kPa (P < 0.01). Gradually a progressive acidosis developed. Moreover, mean arterial blood pressure (MABP) and end-inspiratory airway pressure (Paw) rapidly increased. 3. Concomitantly there was a time-dependent increase of big ET-1 and ET-1 levels in bronchoalveolar lavage (BAL) as determined by combined reverse phase high performance liquid chromatography (h.p.l.c.) and radioimmunoassay. BAL levels of both peptides increased up to 8 min after bicuculline injection and slowly decreased subsequently. In contrast, BAL from animals injected with vehicle did not contain detectable amounts of ET. 4. Pretreatment with the endothelin-converting enzyme inhibitor, phosphoramidon (5.4 mg kg-1, i.v.) for 5 min significantly (P < 0.001) reduced peak ET-1 levels in BAL fluid by 65.4 +/- 9.9% at 8 min after bicuculline injection. Simultaneously it afforded protection from hypoxia. PaCO2 did not increase and PaO2 decreased only slightly from 14.63 +/- 1.00 kPa to 12.97 +/- 0.61 kPa (P > 0.05) after phosphoramidon pretreatment. In contrast, vehicle-treated animals that received bicuculline showed both significant hypercapnia as well as profound hypoxia. Phosphoramidon significantly diminished the maximum increase in Paw by 76.7 +/- 12.4% (P <0.005), but only slightly affected the MABP. Phosphoramidon pretreatment had no effect on the acidosis.5. Pretreatment with the ETA receptor antagonist, BQ-123 (1 mg kg-1, i.v.), for 5 min did not affect the levels of ET-1 in the BAL fluid at 8 min after bicuculline injection but did ameliorate the development of hypoxia. No hypercapnia developed and Pa02 decreased only moderately from 16.65 +/-0.25 kPa to 14.19 +/-2.15 kPa (P>0.05) in BQ-123-treated animals. In contrast, vehicle-treated animals that received bicuculline exhibited significant hypercapnia as well as profound hypoxia. BQ-123 significantly reduced the increase in Paw by 51.3 +/- 12.8% (P < 0.01). It affected MABP only slightly and had no effect on the acidosis.6. These results suggest that ET peptides play a significant role in this model of neurogenic pulmonary oedema and may act as mediators of respiratory distress. The deleterious effects of endogenous ET in this model are primarily mediated via the ETA receptor, for they were inhibited by the ETA receptor antagonist, BQ-123. ETA receptor antagonists may therefore be of potential therapeutic value in respiratory distress.
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PMID:A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats. 854 73

Recently generated knockout mice with disrupted genes encoding endothelin (ET)-1 showed an elevation of arterial blood pressure (AP) and supplied an evidence for intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is yet known, however, why deficiency of ET-1, which was originally found as a potent vasoconstrictor, led to higher AP in these mice. To address this apparent paradox, we first developed a method to measure renal sympathetic nerve activity (RSNA) in mice using rats as reference and successively compared it between normal and ET-1 deficient mice. RSNA was successfully recorded in urethane-anesthetized and artificially ventilated mice by a slight modification of the method used for rats. At basal condition, mean AP (MAP) and RSNA in ET-1 deficient mice (105+/-2 mmHg and 9.71+/-1.49 muVs, n=20) were significantly higher than those in wild-type mice (96+/-2 mmHg and 5. 07+/-0.70 muVs, n=25). Basal heart rate (HR) and baroreflex-control of HR was not significantly different between the two. On the other hand, resting RSNA, RSNA range, and maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA relationship was upwards reset. Hypoxia-induced increase in RSNA was not different between ET-1 deficient (73.4+/-9.4%) and wild-type mice (91.2+/-12.0%), while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice (18.8+/-3.6 vs. 39.1+/-5.2% at 10% CO2). These results indicate that endogenous ET-1 participates in the central chemoreception of CO2 and reflex control of the RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice.
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PMID:Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice. 976 70

1. Exogenously administered endothelin (ET) modulates the activity of cardiovascular and respiratory neurons in the central nervous system (CNS) and, thus, affects arterial blood pressure (ABP) and ventilation. However, a physiological role(s) for endogenous ET in the CNS has not been elucidated. To address this question, we examined ABP and ventilation in mutant mice deficient in ET-1, ETA and ETB receptors and endothelin-converting enzyme-1, which were made by gene targeting. 2. Respiratory frequency and volume was measured in mice by whole body plethysmography when animals breathed normal room air and hypoxic and hypercapnic gas mixtures. A few days after respiratory measurements, a catheter was implanted into the femoral artery under halothane anaesthesia. On the following day, the ABP of awake mice was measured through the indwelling catheter and heart rate was calculated from the ABP signal. After 2 h ABP measurement, arterial blood was collected through the catheter and pH and the partial pressures of O2 and CO2 were measured by a blood gas analyser. 3. Compared with corresponding controls, the mean (+/- SEM) ABP in ET-1+/- and ETB-deficient mice was significantly higher (118 +/- 2 vs 106 +/- 3 mmHg for ET-1+/- (n = 22) and ET-1+/+ (n = 17) mice, respectively; 127 +/- 3 vs 109 +/- 4 mmHg for ETB-/s (n = 9) and ETB+/s (n = 9) mice, respectively; P < 0.05 for both). In ET-1+/- mice, PCO2 tended to be higher and PO2 was significantly lower than corresponding values in ET-1+/+ mice. Under resting conditions, there was no significant difference in respiratory parameters between mutants and their corresponding controls. However, reflex increases of ventilation to hypoxia and hypercapnia were significantly attenuated in ET-1+/-, ET-1-/- and ETA-/- mice. 4. In another series of experiments in ET-1+/- mice, we found that sympathetic nerve activity (SNA) was augmented and reflex excitation of phrenic nerve activity (PNA) in response to hypoxia and hypercapnia was blunted. Attenuation of the reflex PNA response to hypercapnia was also observed in the medulla-spinal cord preparation from ET-1-/- mice. 5. Elevation of ABP in ETB-deficient mice was most likely due to a peripheral mechanism, because SNA and respiratory reflexes were not different from those in control animals. 6. We conclude that endogenous ET-1 plays an important role in the central neural control of circulation and respiration and that ETA receptors mediate this mechanism.
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PMID:Endothelin in the central control of cardiovascular and respiratory functions. 1062 68

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic(99m)Tc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75+/-0.12) and in HV (0.82+/-0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1+/-12.8 ng/24 h and 89.0+/-15.1 ng/24 h) and HV (65.1+/-10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2+/-5.2 ml min(-1)in COPD during exacerbation; 17.5+/-3.9 ml min(-1)at recovery and 13.6+/-2.4 ml min(-1)in HV, P<0.001). GFR was 69.4+/-10.0 ml min(-1)in COPD patients during exacerbation and it significantly increased at the recovery (95.5+/-20.9 ml min(-1)P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=-0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO(2)(r=0.83, P<0.001) and in paO(2)(r=-0.73, P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.
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PMID:Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease. 1144 May 61

Plasma endothelin elevations have been associated with cerebrovascular pathology. Mechanisms of stimulation, however, are unknown. Therefore, in healthy subjects a marked physiological cerebrovascular response was experimentally provoked by hypercapnia, hypocapnia, and alternating capneic conditions. During these challenges plasma immunoreactive-endothelin-1 (ir-ET-1) concentrations were determined using a radioimmunassay. Physiological effects were continuously recorded for pCO(2), cerebral blood flow velocity, pulse frequency, and arterial blood pressure. No alterations in plasma ET-1 levels were found upon any of the cerebrovascular stimuli. We conclude that massive cerebrovascular challenges in healthy individuals do not lead to high circulating ET-1 levels.
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PMID:Effects of cerebrovascular challenges on plasma endothelin. 1206 48

Challenges in the evaluation of the retinal microstructure. To facilitate evaluation of the retinal microstructure we participated in the development of a scanning laser ophthalmoscope (SLO) for 32 years. The 'retro-mode' is the latest developed lateral aperture SLO made in Japan. This instrument enables us to observe the cystoid spaces and retinal microfolds underlying the epiretinal membrane. We investigated the pathogenesis and the mechanism of early development of idiopathic macular holes (MHs) and the vitreomacular interface in idiopathic full-thickness MHs using spectral-domain optical coherence tomography (SD-OCT). We studied the anatomic morphology of stage 1-A impending MHs, characterized by a foveolar yellow spot, using SD-OCT in the fellow eyes of patients diagnosed with a full-thickness MH. SD-OCT showed the reflectivity of the perifoveal posterior vitreous detachment (PVD) with vitreofoveal adhesion in the eyes with a yellow spot; the foveal microstructure had a triangular foveolar detachment of the cone outer segment tip line. The foveolar detachment of the cone outer segment tip line might be responsible for the yellow spot seen in stage 1-A MHs. Using SD-OCT, we also analyzed the vitreomacular interface in idiopathic full-thickness MHs and identified four configurations of the vitreomacular interface in MHs without a complete PVD. The majority, i.e., 92%, of eyes with a MH without a complete PVD are likely due to the anteroposterior vitreofoveal traction exerted by a perifoveal PVD. About 55% of cases with an open roof in the eyes without a complete PVD might be at risk of progression to operculum formation (loss of retinal tissue). 2. Challenges in the evaluation of retinal function SLO microperimetry is used to evaluate the retinal function during observation of the retinal microstructure. We evaluated the retinal sensitivity and the focal visual acuity using our original microperimetry program and clarified the characteristics of the preferred retinal locus (PRL) in macular diseases and the importance of the PRL evaluation. Further refinement of the SLO as an all-in-one instrument with the addition of a treatment feature is planned. We evaluated the retinal blood flow (RBF) using a laser Doppler velocimetry instrument that we developed. In clinical studies, we found that the RBF decreased in patients with type 2 diabetes mellitus with no or mild retinopathy compared with healthy subjects. In in vivo animal studies performed in anesthetized cats, we elucidated the mechanism of RBF regulation in response to physiologic stimuli, i.e., systemic hypoxia, hypercapnia, hyperoxia, hyperglycemia and hypertension. We showed that the retinal vascular endothelium plays an important role in regulating the RBF. In in vitro studies, we examined the effects of laminar shear stress on gene expression in human retinal microvascular endothelial cells (HRMECs) and found that long-term exposure to physiologic shear stress in the retinal arterioles upregulated eNOS and thrombomodulin mRNA expression and down-regulated ET-1 mRNA expression in the HRMECs. In ex vivo studies, we found that simvastatin, pioglitazone, resveratrol and fenofibrate dilated isolated porcine retinal arterioles, suggesting that systemic administration of these drugs may have the therapeutic potential to improve the impaired RBF in patients with type 2 diabetes mellitus. 3. Challenges to the development of a telemedicine support system We established a real-time telemedicine system that can transmit precise retinal images of patients between Asahikawa Medical University Hospital and our branch hospitals. We also developed a method of 3-dimensional high-definition transmission and stereoscopic display for ophthalmology. Moreover, we established a system to share medical information using Peer to Peer technology and network control technology that can transmit urgent information during a disaster. In response to a request from the Chinese Government, which has limited medical facilities in rural areas, we donated our system to four hospitals in Beijing, Shanghai, Sichuan and Shaanxi Provinces. As a result of the development of our unique telemedicine home medical care system, patients can be followed at home even after discharge from a hospital. 4. Conclusions. We believe that ophthalmologists can obtain important information about not only ocular but also systemic diseases by analyzing the retinal microstructure and functions simultaneously and can share this information worldwide via the telemedicine technology that we established, which can be a promising advance in patient care.
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PMID:[Noninvasive analysis of retinal microstructure and function: challenges and a promising future]. 2363 Dec 55