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Blunted vascular re...
Blunted vascular response to endothelin-a receptor blockade in cyclosporine-treated lung transplant recipients
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- Silverborn, Martin, 1969 (author)
- Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute
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- Ambring, Anneli, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Nilsson, Folke, 1950 (author)
- Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute
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- Friberg, Peter, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology
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- Jeppsson, Anders, 1960 (author)
- Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute
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(creator_code:org_t)
- Elsevier BV, 2005
- 2005
- English.
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In: J Heart Lung Transplant. - : Elsevier BV. - 1053-2498. ; 24:6, s. 665-70
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Abstract
Subject headings
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- BACKGROUND: The majority of cyclosporine-treated transplant recipients develop hypertension. Endothelin-1 (ET-1) has been suggested to mediate cyclosporine-induced vasoconstriction when binding to ET-A receptors. We hypothesized that cyclosporine-treated lung transplant recipients have an increased basal vascular resistance and an augmented response to ET-A receptor blockade. METHODS: The selective ET-A receptor blocker BQ-123 (10 and 50 nmol/min) was infused into the brachial artery, alone or in combination with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) (2 and 4 micromol/min) in 10 lung transplant recipients without pharmacologically treated hypertension and 8 healthy controls. Forearm blood flow (FBF) was measured by venous occlusion plethysmography and plasma levels of ET-1 were analyzed. RESULTS: Baseline forearm vascular resistance did not differ between recipients and controls (32 +/- 4 vs 42 +/- 7 mmHg/ml/min, p = 0.32). BQ-123 increased FBF in controls but not in recipients (26% +/- 9% vs 5% +/- 11% at 10 nmol/min, p = 0.043 between groups). Coinfusion of BQ-123 and L-NMMA caused a comparable decrease in FBF in recipients and controls (-26% +/- 11%, vs -34% +/- 7%). Baseline ET-1 was higher in recipients (17.2 +/- 1.1 vs 14.7 +/- 0.8 pg/ml, p = 0.038). BQ-123 infusion increased plasma ET-1 in controls but not in recipients (+24% +/- 11% vs -0.4% +/- 6.2%, p = 0.029 between groups). CONCLUSIONS: The results demonstrate that cyclosporine-treated lung transplant recipients have increased plasma levels of ET-1 and a blunted response to ET-A receptor blockade compared with healthy subjects. In contrast, we found no evidence for an increased basal vascular resistance in transplant recipients. These alterations in endothelin handling may contribute to the development of transplant-associated hypertension.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- Adult
- Antihypertensive Agents/administration & dosage/*pharmacology
- Cyclosporine/therapeutic use
- Female
- Forearm/*blood supply
- Humans
- Immunosuppressive Agents/therapeutic use
- Infusions
- Intra-Arterial
- *Lung Transplantation
- Male
- Middle Aged
- inhibitors/pharmacology
- Peptides
- Cyclic/administration & dosage/*pharmacology
- Receptor
- Endothelin A/*antagonists & inhibitors
- Regional Blood Flow/drug effects
- Vascular Resistance/*drug effects
- omega-N-Methylarginine/administration & dosage/pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
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