Vasodilator effect of endothelin in cutaneous microcirculation of heart failure patients.
The heart failure syndrome is associated with a reduced vasodilatory capacity in cutaneous microvessels. The aim of this study was to investigate the hypothesis that an altered activity of the endothelin system contributes to this reduction. The skin blood flow was recorded by laser Doppler flowmetry in patients with congestive heart failure and in age- and gender-matched controls without clinical signs of heart failure. The vessels were stimulated by iontophoretic administration of endothelin-1. The involvement of the endothelin(A) receptor was studied by co-administration of a specific antagonist; the role of the endothelin(B) receptor was studied by the administration of the selective agonist sarafotoxin 6c. The plasma levels of endothelin-1, C-reactive peptide and N-terminal-pro-Brain Natriuretic Peptide were elevated in heart failure patients. Unexpected, endothelin-1 induced an endothelin(A) mediated vasodilation. In the heart failure group the dilation was reduced to less than half as compared to control. The response to local warming was reduced in parallel indicating that the attenuation of the response in the heart failure group can be explained by the general decline in vascular reactivity. The response to endothelin(B) receptor stimulation did not differ between the groups. The reduction in endothelin-1 responsiveness is paralleled by a general reduction in microvascular vasodilatory capacity, a phenomenon of increased vascular stiffness in the of heart failure subjects.
Department of Internal Medicine, Lund University, Lund, Sweden. Sven.Anderson@skane.se
Sven E
SE
Andersson
Marie-Louise
ML
Edvinsson
Kjell
K
Alving
Lars
L
Edvinsson
D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007478:Iontophoresis; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D044023:Receptor, Endothelin B / Q000819:agonists; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000378:metabolism
D015415:Biomarkers; D008078:Cholesterol, LDL; D016232:Endothelins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D014757:Viper Venoms; C109794:pro-brain natriuretic peptide (1-76); C057354:sarafotoxins s6; D020097:Natriuretic Peptide, Brain