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PubMed · 11078358

Active immunization against endothelin-1 is associated with a decrease in plasma endothelin-1 and changes in vascular reactivity.

M A Grafov·S A Gavrilova·Rubina AYu·V P Masenko·N A Medvedeva
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Abstract

Exogenous endothelin-1 (ET-1) or high concentrations of the peptide in pathological conditions have marked effects on vascular reactivity. In order to evaluate the role of endogenous ET-1 we investigated responsiveness of conduit (aorta) and of resistant-like (tail artery) vessels in ET-1-deficient rats. Elimination of circulating ET-1 was achieved by active immunization of Wistar rats with a peptide-haemocyanin conjugate (anti-ET-1 group), leading to a marked reduction in plasma level of the peptide in comparison with that of vehicle-treated animals (control group): 1.9 fmol/ml vs 4.9 fmol/ml, respectively. The immunization was associated with a slight elevation of mean arterial pressure, whereas heart rate remained unchanged. In the anti-ET-1 group rings of isolated aorta displayed reduced sensitivity to ET-1: EC50 = 6.57 nM vs 2.95 nM in the control group. Tail arteries of the ET-1-deficient rats showed diminished responses to ET-1, 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 endothelium-dependent relaxation to acetylcholine (Ach, EC50 = 0.20 microM vs 0.35 microM in the control group), whereas experiments on perfused tail artery showed a twofold reduction in Ach effects. Thus, depletion of circulating ET-1 induces slight changes in haemodynamics associated with altered vessel responsiveness to vasoactive substances.

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AcetylcholineAnimalsDose-Response Relationship, DrugEndothelin-1In Vitro TechniquesMaleRatsRats, WistarVaccinationVasoconstrictionJournal ArticleResearch Support, Non-U.S. Gov't

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M A Grafov, S A Gavrilova, Rubina AYu, V P Masenko, N A Medvedeva. 2000. Active immunization against endothelin-1 is associated with a decrease in plasma endothelin-1 and changes in vascular reactivity.. https://doi.org/10.1097/00005344-200036051-00042

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