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 path ological conditions have marked effects on vascular reactivity. In order to evaluate the role of endogenous ET-1 we investigated responsiveness of con duit (aorta) and of resistant-like (tail artery) vessels in ET-1-deficient rats. Elimination of circulating ET-1 was achieved by active immunization o f Wistar rats with a peptide-haemocyanin conjugate (anti-ET-1 group), leadi ng 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: E C50 = 6.57 nM vs 2.95 nM in the control group. Tail arteries of the ET-1-de ficient rats showed diminished responses to ET-1, the maximal rise in perfu sion pressure: +5.2 mmHg vs +13.6 mmHg in the control group. After immuniza tion, rings of isolated aorta displayed no changes in endothelium-dependent relaxation to acetylcholine (Ach, EC50 = 0.20 muM vs 0.35 muM in the contr ol group), whereas experiments on perfused tail artery showed a twofold red uction in Ach effects. Thus, depletion of circulating ET-1 induces slight c hanges in haemodynamics associated with altered vessel responsiveness to va soactive substances.