UMLS:C0020440 - FACTA Search

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Query: UMLS:C0020440 (hypercapnia)
7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Pithed rats were respired at a fixed rate of 54 cycles min-1 and with a ventilation volume of either 20 (control) or 10 ml kg-1. In these two preparations, the dose-response relationships for the systemic blood pressure responses to endothelin-1, administered i.v., were examined. Also, cardiac output, its distribution, tissue blood flows and vascular resistances were determined at both respiratory volumes in pithed rats given saline or during pressor responses to endothelin-1 (750 ng, i.v.). Finally, a comparison was made of the pressor responses to endothelin-1 in the blood perfused superior mesenteric arterial bed of pithed rats respired at 10 or 20 ml kg-1. 2. In control rats the systemic blood pressure responses to i.v. endothelin-1 were biphasic with an initial, transient (30 s) decrease in blood pressure followed by a well sustained pressor response. These responses were dose-dependent (the ED50 for the pressor response being 0.27 +/- 0.04 micrograms). The pressor effect of endothelin-1 was due to an increase in total peripheral resistance with no change in heart rate or cardiac output. This increased total peripheral resistance was due to vasoconstriction of the spleen, stomach, large intestine, small intestine and the pancreas/mesentery (in which it was most severe). Endothelin-1 also increased blood flow through the heart, lungs, liver, epididimides, fat and skin through redistribution of cardiac output to these vascular beds. 3. At the lower ventilation volume there was moderate acidosis, hypoxia and hypercapnia relative to those rats respired at 20 ml kg-1. With respiration at 10 ml kg-1, the pressor response to endothelin-1 was not sustained and, after oscillations in both blood pressure and heart rate, death occurred 15-20 min after administration. The pressor effect resulted from increases in cardiac output (due to increased stroke volume) and total peripheral resistance: the latter was caused by vasoconstriction in the stomach, small intestine, large intestine and pancreas/mesentery. Endothelin-1 increased blood flow through the heart, lungs, liver, kidneys, testes, fat and skin due to either an increase in cardiac output, redistribution of cardiac output or both. 4. Endothelin-1 induced dose-dependent pressor responses in the mesenteric bed in situ. At the lower ventilation volume the potency of endothelin-1 in this vascular bed was increased approximately two fold with the ED50 being 68 +/- 7 pmol compared to 113 +/- 15 pmol in the rats respired at 20 ml kg-1. 5. This study indicates that, in normoxic control pithed rats, the pressor response to endothelin-1 was due largely to vasoconstriction of the splanchnic vascular bed. In rats with moderate hypoxia, hypercapnia and acidosis, the pressor response was due to vasoconstriction of the gastrointestinal tract as well as an increase in cardiac output. Endothelin-1 induced profound vasoconstriction in the mesenteric bed of the pithed rat both in vivo and in situ. The potency of endothelin-1 on this bed in situ was doubled by lowering the ventilation volume. An increase in cardiac contractility and severe gastrointestinal vasoconstriction may be the initial events leading to the eventual toxic effect of endothelin-1 in the hypoxic pithed rat.
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PMID:Effects of moderate hypoxia, hypercapnia and acidosis on haemodynamic changes induced by endothelin-1 in the pithed rat. 251 90

We studied respiratory functions in mutant mice deficient in endothelin-1 (ET-1) generated by gene targeting. In conscious adult mice heterozygous for ET-1 gene mutation (ET+/- heterozygous mice), arterial PO2 was significantly lower, PCO2 tended to be higher, and pH tended to be lower than in wild-type littermates. When these conscious mice breathed room air, respiratory minute volume and rate, determined by body plethysmography, were not significantly different between the two groups. However, when ET+/- heterozygous mice were subjected to systemic hypoxia (1:1 air-N2) or hypercapnia (5% CO2-95% O2), increases in respiratory minute volume were significantly attenuated. In conscious newborn ET-/- homozygous mice delivered by cesarean section and tracheotomized, ventilatory responses to systemic hypoxia and hypercapnia, regularly observed in newborn wild-type mice, were almost totally absent. In urethan-anesthetized adult ET+/- heterozygous mice, increases in phrenic nerve discharges in response to hypoxia and hypercapnia were significantly attenuated. Our results demonstrate that ventilatory responses to hypoxia and hypercapnia are impaired in ET-1-deficient mice and suggest that endogenous ET-1 participates in the physiological control of ventilation.
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PMID:Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1. 876 95

Global cerebral ischemia and subsequent reperfusion induce early impairment of the vasodilator responses to hypercapnia and vasoactive substances. Nitric oxide (NO) is involved in the regulation of cerebral blood flow (CBF) in both health and disease. The present study was designed to assess possible changes in the cerebrovascular reactivity to NO donors induced by cerebral ischemia-reperfusion in goats. Female goats (n = 9) were subjected to 20 min global cerebral ischemia under halothane/N2O anesthesia. Sixteen additional goats were sham-operated as a control group. One week later the effects of ischemia-reperfusion on relaxations to NO donors sodium nitroprusside (SNP), diethylamine/NO (DEA/NO), diethylenetriamine/NO (DETA/NO), and spermine/NO (SPER/NO) were studied in rings of middle cerebral artery (MCA) isolated in an organ bath for isometric tension recording. SNP, DEA/NO, DETA/NO, and SPER/NO induced concentration-dependent relaxations of MCA precontracted with KCl (DEA/NO > SPER/NO > SNP > DETA/NO) or with endothelin-1 (DEA/NO > SNP > SPER/NO > DETA/NO). Relaxations were always higher in endothelin-1-precontracted arteries. One week after cerebral ischemia concentration-response curves to SNP and DEA/NO were displaced to the right, indicating a reduction in relaxant potency of NO donors. The classical nitrovasodilator SNP and NONOates induce relaxation of isolated goat MCA which is partially inhibited by arterial depolarization. Global cerebral ischemia followed by reperfusion induces delayed impairment of the relaxant effects of NO on cerebrovascular smooth muscle, which results in reduced vasodilatory potency of NO donors in large cerebral arteries.
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PMID:Relaxant effects of sodium nitroprusside and NONOates in goat middle cerebral artery: delayed impairment by global ischemia-reperfusion. 1035 99

Clinical studies suggest that sleep apnea causes systemic hypertension. In addition, patients with sleep apnea have elevated plasma levels of endothelin-1 (ET-1). We hypothesized that the intermittent hypoxia/hypercapnia (IH) associated with sleep apnea causes hypertension by increasing ET-1 production. To test this hypothesis, rats with arterial and venous catheters were placed in Plexiglas chambers. IH rat chambers were flushed with an N(2)-CO(2) mixture for 90 seconds to achieve hypoxia/hypercapnia (5% O(2)-5% CO(2)) followed by 90 seconds of compressed air to achieve normoxia (21% O(2)-0% CO(2)). Control rat chambers were flushed with 90 seconds of air-air cycles. Cycles for both groups were repeated 8 hours per day for 11 days. Resting mean arterial pressure (MAP) and heart rate were recorded daily before the start of exposure. After 11 days, MAP was significantly elevated in IH rats compared with initial MAP (109+/-5 mm Hg initial, 139+/-11 mm Hg day 11) and compared with air-air rats (110+/-4 mm Hg). On day 11, cumulative doses of PD145065 (a nonselective ET-receptor antagonist) were administered intravenously to the rats breathing room air. PD145065 caused a dose-dependent decrease in MAP in IH rats but did not alter MAP in air-air rats. Plasma ET-1 measured by radioimmunoassay was significantly increased on days 5 and 11 in the IH rats compared with day 1 and compared with air-air rats. There was no significant change in plasma ET-1 over time in air-air rats. We conclude that IH exposure increases both MAP and plasma ET-1 and that the increased ET-1 may contribute to the hypertension.
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PMID:Role of endothelin in intermittent hypoxia-induced hypertension. 1123 Mar 27

Endothelin-converting-enzyme (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to mature endothelin-1. Most homozygous ECE-1-/- embryos die in utero and show severe craniofacial, enteric, and cardiac malformations precluding ventilatory function assessment. In contrast, heterozygous ECE-1+/- embryos develop normally. Their respiratory function at birth has not been studied. Taking into account previous respiratory investigations in mice with endothelin-1 gene disruption, we hypothesized that ECE-1-deficient mice may have impaired ventilatory control. We analyzed ventilatory responses to hypercapnia (8% CO(2)) and hypoxia (10% O(2)) in newborn and adult mice heterozygous for ECE-1 deficiency (ECE-1+/-) and in their wild-type littermates (ECE-1+/+). Ventilation, breath duration, and tidal volume were measured using whole-body plethysmography. Ventilatory responses to hypoxia were significantly weaker in ECE-1+/- than in ECE-1+/+ newborn mice (percentage ventilation increase: 1 +/- 25% versus 33 +/- 29%, p = 0.010). Baseline breathing variables and ventilatory responses to hypercapnia were normal in the ECE-1+/- newborn mice. No differences were observed between adult ECE-1+/- and ECE-1+/+ mice. We conclude that ECE-1 is required for normal ventilatory response to hypoxia at birth.
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PMID:Impaired ventilatory responses to hypoxia in mice deficient in endothelin-converting-enzyme-1. 1132 56

We recently concluded that constriction of basilar artery due to respiration-induced hypocapnia in rabbits with acute metabolic alkalosis and accompanying compensatory hypercapnia was independent of NO and K(ATP) channels. Based on reports that endothelin-1-mediated hypocapnic constriction of the rabbit basilar artery in vitro, we further investigated whether the respiration-induced hypocapnic constriction was endothelin-1 mediated. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. The ET(A) plus ET(B) receptor antagonist, PD145065 (1 microM), and the selective ET(A) receptor antagonist, BQ610 (3 microM), completely relaxed the hypocapnic constriction, as determined in a cranial window. Unexpectedly, the ET(B) receptor antagonists, BQ788 and RES-701-1 (3 microM), relaxed the constriction by 72.1+/-2.8% (4) and 77.2+/-8.7% (5), respectively (means+/-S.E. (n)). To investigate whether the large magnitudes of relaxation to both ET(A) and ET(B) receptor antagonists were due to nonselectivity of the antagonists, the effects of the antagonists on the constriction to exogenous endothelin-1 were evaluated. BQ610, BQ788, and RES-701-1 relaxed the 3-5 nM endothelin-1 constriction by only 64.3+/-7.6% (4), 43.5+/-8.5% (5), and 26.7+/-4.8% (3) (means+/-S.E. (n)), respectively, consistent with the selective blocking action of these antagonists. To investigate whether the greater magnitude of BQ610, BQ788, and RES-701-1 relaxation of hypocapnic constricted versus exogenous endothelin-1-constricted vessels was due to differences between constriction elicited by endogenous versus exogenous endothelin-1, the effects of the endothelin receptor antagonists on constriction to isocapnic alkaline suffusate were evaluated. PD145065 (1 microM) and 0.1 mM phosphoramidon, an endothelin-converting enzyme inhibitor, inhibited the constriction to isocapnic alkaline suffusate by 83.8+/-7.8% (6) and 74.3+/-9.7% (8) (means+/-S.E. (n)), respectively, consistent with the endothelin-1 dependency of the constriction. BQ610, BQ788, and RES-701-1 relaxed the isocapnic alkaline suffusate constriction by 74.9+/-6.7% (5), 65.5+/-6.4% (5), and 78.0+/-6.5% (4) (means+/-S.E. (n)), respectively. Thus, the relaxation profile to the selective endothelin receptor antagonists in isocapnic alkaline constricted vessels more closely approximated the relaxation profile observed in hypocapnic constricted as compared to endothelin-1-constricted vessels. Hypocapnia did not alter the 5 nM endothelin-1 constriction. These results suggest that, under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent hypocapnic constriction is endothelin mediated. Both ET(A) and ET(B) receptor activation may mediate the hypocapnic constriction. The hypocapnic constriction is not due to enhanced endothelin-1 constriction and, thus, is due to the release of endothelin-1 and/or additional endothelins.
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PMID:Reversal of hypercapnia induces endothelin-dependent constriction of basilar artery in rabbits with acute metabolic alkalosis. 1192 64

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

We reported previously that simulating sleep apnea in rats by exposing them 7 hours per day to intermittent hypoxia/hypercapnia (IH) elevates plasma endothelin-1 and causes hypertension, which is reversed by an endothelin-1 antagonist. We hypothesized that in this model of sleep apnea-induced hypertension, vascular sensitivity to endothelin-1 is increased in combination with the elevated plasma endothelin-1 to cause the endothelin-1-dependent hypertension. In small mesenteric arteries with endothelial function disabled by passing air through the lumen, diameter and vessel wall [Ca2+] were recorded simultaneously. IH arteries demonstrated increased constrictor sensitivity to endothelin-1 (percentage max constriction 100+/-0% IH versus 80+/-10% Sham; P<0.05). This was accompanied by increased calcium sensitivity of IH arteries. In contrast, constrictor sensitivity and increases in vessel wall [Ca2+] to KCl and phenylephrine were not different between IH and Sham arteries. We have shown previously that endothelin-1 constriction in mesenteric arteries is mediated by endothelin A receptors. In the current study, the selective increase in endothelin-1 constriction in IH resistance arteries was accompanied by increased expression of endothelin A receptor expression (densitometry units 271+/-23 IH versus 158+/-25 Sham; P<0.05). Thus, IH hypertension appears to cause alterations in signaling components unique to endothelin-1 at the receptor level and in postreceptor signaling that increases calcium sensitivity during endothelin A activation. Future studies will determine the specific changes in vascular smooth muscle signaling in IH hypertension causing this augmented contractile phenotype.
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PMID:Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. 1573 50

Induction of hypercapnia by breathing high concentrations of carbon dioxide (CO(2)) may have beneficial effects on the pulmonary circulation. We tested the hypothesis that exposure to CO(2) would protect against chronic pulmonary hypertension in newborn rats. Atmospheric CO(2) was maintained at <0.5% (normocapnia), 5.5%, or 10% during exposure from birth for 14 days to normoxia (21% O(2)) or moderate hypoxia (13% O(2)). Pulmonary vascular and hemodynamic abnormalities in animals exposed to chronic hypoxia included increased pulmonary arterial resistance, right ventricular hypertrophy and dysfunction, medial thickening of pulmonary resistance arteries, and distal arterial muscularization. Exposure to 10% CO(2) (but not to 5.5% CO(2)) significantly attenuated pulmonary vascular remodeling and increased pulmonary arterial resistance in hypoxia-exposed animals (P < 0.05), whereas both concentrations of CO(2) normalized right ventricular performance. Exposure to 10% CO(2) attenuated increased oxidant stress induced by hypoxia, as quantified by 8-isoprostane content in the lung, and prevented upregulation of endothelin-1, a critical mediator of pulmonary vascular remodeling. We conclude that hypercapnic acidosis has beneficial effects on pulmonary hypertension and vascular remodeling induced by chronic hypoxia, which we speculate derives from antioxidant properties of CO(2) on the lung and consequent modulating effects on the endothelin pathway.
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PMID:Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat. 1682 30

There have been contradictory reports suggesting that CO(2) may constrict, dilate, or have no effect on pulmonary vessels. Permissive hypercapnia has become a widely adopted ventilatory technique used to avoid ventilator-induced lung injury, particularly in patients with acute respiratory distress syndrome (ARDS). On the other hand, respiratory alkalosis produced by mechanically induced hyperventilation is the mainstay of treatment for newborn infants with persistent pulmonary hypertension. It is important to clarify the vasomotor effect of CO(2) on pulmonary circulation in order to better evaluate the strategies of mechanical ventilation in intensive care. In the present study, pulmonary vascular responses to CO(2) were observed in isolated rat lungs (n = 32) under different levels of pulmonary arterial pressure (PAP) induced by various doses of endothelin-1 (ET-1). The purposes of this study were to investigate (1) the vasodilatory effect of 5% CO(2) in either N(2) (hypoxic-hypercapnia) or air (normoxic-hypercapnia) at different PAP levels induced by various doses of endothelin-1, and (2) the role of nitric oxide (NO) in mediating the pulmonary vascular response to hypercapnia, hypoxia, and ET-1. The results indicated that (1) CO(2) produces pulmonary vasodilatation at high PAP under ET-1 and hypoxic vasoconstriction; (2) the vasodilatory effect of CO(2) at different pressure levels varies in accordance with the levels of PAP, the dilatory effect tends to be more evident at higher PAP; and (3) endogenous NO attenuates ET-1 and hypoxic pulmonary vasoconstriction but does not augment the CO(2)-induced vasodilatation.
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PMID:Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1. 2021 11

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