Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats

Shirakami, Gotaro; Nakao, Kazuwa; Saito, Yoshihiko; Magaribuchi, Tatsuo; Jougasaki, Michihisa; Mukoyama, Masashi; Arai, Hiroshi; Hosoda, Kiminori; Suga, Shin Ichi; Ogawa, Yoshihiro; Yamada, Takayuki; Mori, Kenjiro; Imura, Hiroo

doi:10.1016/0024-3205(91)90362-f

Cited by 136 publications

(67 citation statements)

References 24 publications

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“…ET-1 has been shown to be a potent pulmonary vasoconstrictor [5]. Acute pulmonary alveolar hypoxia increases lung and plasma ET-1 levels, which were parallel to the severity of hypoxia in conscious unrestrained rats [12] and human [4]. In the present case, the plasma ET-1 levels in both systemic and pulmonary arteries on admission were higher than at recovery, suggesting that ET-1 could be partially responsible for the pulmonary hypertension.…”

Section: Discussionsupporting

confidence: 51%

Endothelin-1 and interleukin-8 in high altitude pulmonary oedema

Droma

Hayano²,

Takabayashi³

et al. 1996

Eur Respir J

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E En nd do ot th he el li in n--1 1 a an nd d i in nt te er rl le eu uk ki in n--8 8 i in n h hi ig gh h a al lt ti it tu ud deABSTRACT: We present a case of high altitude pulmonary oedema (HAPE) with pulmonary hypertension and polymorphoneuclear leucocyte (PMN) accumulation in bronchoalveolar lavage fluid (BALF), which occurred in a 21 year old man. Plasma endothelin-1 (ET-1) and interleukin-8 (IL-8) concentration in BALF were elevated on admission, and returned to normal level at recovery, when the pulmonary artery pressure and the PMN counts in BALF were normal. In addition, E-selectin and intercellular adhesion molecule-1 (ICAM-1) in BALF were also slightly increased on admission.These findings suggest that endothelin-1 is a vasoconstrictor which contributes to the pulmonary hypertension in high altitude pulmonary oedema, and that some of the inflammatory mediators play an important role in chemotaxis and accumulation of polymorphonuclear leucocytes in the development of high altitude pulmonary oedema. Eur Respir J., 1996Respir J., , 9, 1947Respir J., -1949. High altitude pulmonary oedema (HAPE) is a severe type of acute mountain sickness. It is a serious, sometimes fatal illness related to rapid exposure to altitude. Although the pathophysiological mechanism of HAPE remains unclear, it has long been suggested that pulmonary vasoconstriction and increased pulmonary vascular permeability are important contributory factors [1,2]. Recent studies have suggested that endothelin is related to pulmonary vasoconstriction [3][4][5], and that the increased pulmonary vascular permeability is probably caused by inflammatory mediators [6][7][8][9][10]. However, no studies have been conducted on the role of endothelin and cytokines in patients with HAPE. We report a case of HAPE, documenting the possible role of endothelin-1 (ET-1), and polymorphoneuclear leucocyte (PMN) chemotactic mediators, such as interleukin-8 (IL-8). Case reportA Japanese male university student, aged 21 yrs, who was healthy before climbing, arrived at the foot of the Japan Alps at 1,000 m above sea level. The next morning, he started climbing to a snowy valley about 2,000 m above sea level and still felt well. On the third day, whilst climbing to Mt Yari (3,180 m), he developed general fatigue, followed by headache, cough, sputum, poor appetite and fever (38˚C). After staying all day to rest at 3,000 m, his condition progressively deteriorated. On the fifth day, he was lethargic, comatose, cyanotic, and had a cough with foamy sputum. He was rescued, transported by helicopter, and admitted to our Shinshu University Hospital (660 m).On admission, he had cyanosis and was unconscious. His temperature was 38˚C, pulse rate 140 beats·min -1 , respiration rate 26 breaths·min -1 , and his blood pressure 140/90 mmHg. Coarse crackles were audible over both sides of the lung. He showed decerebrate rigidity. An examination of the ocular fundi showed papilloedema and multiple flame-shaped and blot haemorrhages in both fundi. A chest roentgenogram revealed patc...

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Section: Discussionsupporting

confidence: 51%

Endothelin-1 and interleukin-8 in high altitude pulmonary oedema

Droma

Hayano²,

Takabayashi³

et al. 1996

Eur Respir J

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“…Serum levels of vasopressin, e.g. which is known to induce activation of PKC in hepatocytes [28], were found to increase in hypoxia-exposed rats [46], and it is conceivable that such an increase may partially counteract a rise in EPO mRNA.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

et al. 1994

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Abstract.To define the role of protein kinase C (PKC) in oxygen-dependent production of erythropoietin (EPO) in the liver, we have determined EPO messenger ribonucleic acid (mRNA) expression in primary cultures of juvenile rat hepatocytes incubated at different oxygen tensions in the absence and presence of phorbol esters, vasopressin, and structurally different kinase inhibitors. Upon reduction of oxygen concentrations from 40% to 3% EPO mRNA in cultured hepatocytes increased markedly within 1.25 h, reached maximal values after 2.5 h and remained elevated for up to 72 h. Treatment of hepatocytes during 1.25-5 h of hypoxic exposure with phorbol 12-myristate-13 acetate (PMA) attenuated hypoxiainduced EPO mRNA levels dose-dependently by a maximum of approximately 50%. This inhibitory effect of PMA disappeared upon treatment for more than 5 h and was completely lost after incubation for 9 and 18 h in the presence of 10 -6 M and 10 -7 M PMA, respectively. Phorbol 12,13-dibutyrate and vasopressin also inhibited EPO mRNA accumulation, whereas 4 alpha-phorbol 12,13-didecanoate was ineffective. Western blot analysis of PKC isozymes revealed the presence of PKC alpha, beta II, delta, epsilon and zeta and provided no evidence that the PMA-induced inhibition of EPO expression was associated with depletion of any of these isozymes. Conversely, PMA-induced inhibition of EPO mRNA accumulation was paralleled by translocation of PKC alpha from cytosol to membranes and the time-and dose-dependent attenuation of the inhibitory effect of PMA on EPO mRNA levels was paralleled by down-regulation of PKC alpha. A dose-dependent inhibition of EPO mRNA formation, independent of effects on total RNA synthesis, as determined by [3H]uridine incorporation, was also found in the presence of the kinase inhibitor staurosporine (EDso --2 • 10 s M) and three structurally related derivatives with increased selectivity for PKC (RO 317549, EDso --1 • -6 M; RO 318220, EDso --lX

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“…The transient increase in plasma endothelin-1 levels may conceivably relate to stimulation by factors such as cortisol, 29 which shows a concomitant tendency to rise in the present study, or to a reduction in shear stress and/or tissue oxygen concentrations after the AMinduced fall in blood pressure (from already reduced levels)-both of which are reported to enhance endothelin secretion. 30,31 The acute rise in endothelin is unlikely to be owing to a direct effect of AM, given that the peptide has been shown to inhibit endothelin production in vascular smooth muscle cells. 32 Indeed, increasing evidence indicates the existence of a paracrine/autocrine regulatory loop between AM and endothelin, with recent findings demonstrating that stimulation of the endothelin type B receptor induces the synthesis and secretion of AM in canine aortic endothelial cells, 33 suggesting the peptide may function to buffer the vasoconstrictor effect of endothelin.…”

Section: Chronic Effects Of Adrenomedullin In Sheep With Experimentalmentioning

confidence: 99%

Long-Term Adrenomedullin Administration in Experimental Heart Failure

et al. 2002

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Abstract-Short-term administration of adrenomedullin, a recently discovered peptide with potent vasodilator, natriuretic, and aldosterone-inhibitory actions, has beneficial effects in experimental and clinical heart failure. The effects of prolonged adrenomedullin administration have not previously been assessed in this setting. Consequently, in 16 sheep with pacing-induced heart failure, we infused either adrenomedullin (10 ng/kg per minute; nϭ8) or a vehicle control (Hemaccel; nϭ8) for 4 days. Compared with control data, infusion of adrenomedullin persistently increased circulating levels of the peptide (by Ϸ9.5 pmol/L; PϽ0.001), in association with prompt (15 minutes) and sustained (4 days) increases in cardiac output (day 4, 27%), and reductions in peripheral resistance (30%), mean arterial pressure (13%), and left atrial pressure (24%; all, PϽ0.001). Adrenomedullin also significantly enhanced urinary sodium excretion (day 4, 3-fold; PϽ0.05), creatinine excretion (1.2-fold; PϽ0.001), and creatinine clearance (1.4-fold; PϽ0.001) over the 4 days of treatment, whereas urine volume and cAMP excretion tended to be elevated (both, 0.1ϾPϾ0.05). Plasma renin activity was increased (PϽ0.05), whereas aldosterone levels were reduced in a sustained fashion (PϽ0.01). Plasma endothelin rose transiently (hours 1 to 6) after initiation of treatment (PϽ0.05). Despite substantial cardiac unloading, plasma concentrations of the natriuretic peptides were not significantly different from control. In conclusion, long-term administration of adrenomedullin induces pronounced and sustained cardiovascular and renal effects in experimental heart failure, including reductions in cardiac preload and afterload, as well as augmentation of cardiac output, sodium excretion, and glomerular filtration. These findings support the concept of adrenomedullin as a protective hormone during hemodynamic compromise with therapeutic potential in heart failure.

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Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats

Cited by 136 publications

References 24 publications

Endothelin-1 and interleukin-8 in high altitude pulmonary oedema

Endothelin-1 and interleukin-8 in high altitude pulmonary oedema

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

Long-Term Adrenomedullin Administration in Experimental Heart Failure

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