Active Immunization Against Endothelin1 is Associated With a Decrease in Plasma Endothelin1 and Changes in Vascular Reactivity

Autor: Grafov, Mikhail A., Gavrilova, Svetlana A., Rubina, Alla Yu, Masenko, Valerii P., Medvedeva, Natalija A.
Zdroj: Journal of Cardiovascular Pharmacology; January 2000, Vol. 36 Issue: Supplement 1 pS132S134-S132S134, 1p
Abstrakt: Exogenous endothelin1 ET1 or high concentrations of the peptide in pathological conditions have marked effects on vascular reactivity. In order to evaluate the role of endogenous ET1 we investigated responsiveness of conduit aorta and of resistantlike tail artery vessels in ET1deficient rats. Elimination of circulating ET1 was achieved by active immunization of Wistar rats with a peptidehaemocyanin conjugate antiET1 group, leading to a marked reduction in plasma level of the peptide in comparison with that of vehicletreated animals control group 1.9 fmolml vs 4.9 fmolml, respectively. The immunization was associated with a slight elevation of mean arterial pressure, whereas heart rate remained unchanged. In the antiET1 group rings of isolated aorta displayed reduced sensitivity to ET1 EC506.57 nM vs 2.95 nM in the control group. Tail arteries of the ET1deficient rats showed diminished responses to ET1, the maximal rise in perfusion pressure 5.2 mmHg vs 13.6 mmHg in the control group. After immunization, rings of isolated aorta displayed no changes in endotheliumdependent relaxation to acetylcholine Ach, EC500.20 M vs 0.35 M in the control group, whereas experiments on perfused tail artery showed a twofold reduction in Ach effects. Thus, depletion of circulating ET1 induces slight changes in haemodynamics associated with altered vessel responsiveness to vasoactive substances.
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