Search

Activation of the endothelin (ET) ET B receptor can mediate opposite effects, endothelium-dependent vasodilation but also direct vasoconstriction. So far one gene encoding an ET B receptor has been identified and associated with endothelium-dependent relaxation. It has been suspected that the presence of another ET B gene could explain ET B - mediated contraction. The goal of the present study was to evaluate in Piebald-lethal (s 1 ) mice, a naturally occurring mutant with deletion of the known ET B receptor gene, whether ET B receptor-mediated constriction is lost. Piebald-lethal (s 1 ) mice, in contrast to control mice, completely lacked ET B specific ligand binding. The pressor effect of the ET B receptor selective agonist sarafotoxin S6c was completely absent. In vitro, contraction of stomach strips induced by sarafotoxin S6c was also abolished in Piebald-lethal (s 1 ) mice. These results demonstrate the responsibility of the known ET B receptor gene in ET B -mediated constriction.

ACE inhibition has been shown to prevent neointima formation after vascular injury. However, it is not known if this effect is due to a specific inhibition of the renin angiotensin system or to another mechanism such as the accumulation of bradykinin. In order to answer this question we compared the effects of maximal effective doses of cilazapril, an angiotensin converting enzyme (ACE) inhibitor, and ciprokiren, a new renin inhibitor, in guinea pigs. Vascular injury was induced by endothelial denudation of the right carotid artery of guinea pigs treated either by saline (control group), cilazapril (30 mg/kg/day) or ciprokiren (24 mg/kg/day). Twelve days after the ballooning, the guinea pigs were sacrificed, the carotid arteries were perfused fixed and neointima formation was evaluated by quantitative morphometry. Both, ciprokiren and cilazapril prevented neointima formation to the same extent (inhibition by 42 and 49%, respectively, p These results suggest that, in guinea pigs, renin inhibition prevents neointima formation to a similar extent as ACE inhibition. Therefore, ACE inhibitors seem to act in this model by inhibiting the renin angiotensin system and not by other effects such as accumulation of bradykinin.