Blunted vascular response to endothelin-a receptor blockade in cyclosporine-treated lung transplant recipients

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Blunted vascular response to endothelin-a receptor blockade in cyclosporine-treated lung transplant recipients

Silverborn, Martin, 1969 (author): Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute

Ambring, Anneli, 1964 (author): Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology

Nilsson, Folke, 1950 (author): Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute

Friberg, Peter, 1956 (author): Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi,Institute of Physiology and Pharmacology, Dept of Physiology

Jeppsson, Anders, 1960 (author): Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute

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Elsevier BV, 2005
2005
English.
In: J Heart Lung Transplant. - : Elsevier BV. - 1053-2498. ; 24:6, s. 665-70

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Surgery

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By the university: University of Gothenburg

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