Active immunization against endothelin-1 is associated with a decrease in plasma endothelin-1 and changes in vascular reactivity.
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.
Grafov
M A
MA
Department of Pharmacology, Faculty of Basic Medicine, Lomonosov Moscow State University, Vorobjovy Gory, Russia. mgrafov@fbm.msu.ru
Gavrilova
S A
SA
Rubina AYu
Masenko
V P
VP
Medvedeva
N A
NA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014611:Vaccination; D014661:Vasoconstriction / Q000187:drug effects*
D019332:Endothelin-1; D000109:Acetylcholine