Arterial stiffness is a key determinant of cardiovascular risk. We have shown previously that endogenous endothelin-1 (ET-1), acting via endothelin A (ET_A) receptors, directly regulates large artery stiffness in vivo [1]. However, the contribution of endothelin B (ET_B) receptors to this response has not been described. Therefore, the aim of this study was to investigate the role of ET_B receptors in the regulation of arterial stiffness.

All studies were conducted in anaesthetized sheep, with the approval of the University of New South Wales Animal Care and Ethics Committee. PWV was calculated using the foot-to-foot methodology from two pressure waveforms simultaneously recorded with a high fidelity, dual pressure-sensing catheter placed in the common iliac artery. In five sheep, following baseline recordings, the selective ET_B receptor agonist, sarafotoxin 6c (S6c, 7.5 pmol min^-1), was infused for 60 min and in five sheep, exogenous ET-1 (10 pmol min^-1) was infused for 60 min. In a further five sheep, the selective ET_B receptor antagonist, BQ-788 (1 nmol min^-1) was infused for 45 min, followed by saline for 30 min.

Intra-arterial infusion of the ET_B receptor agonist, S6c, had no effect on the PWV (change of 0 ± 6%, mean ± SD, P = 0.8). In contrast, exogenously infused ET-1 significantly increased the PWV by 11 ± 3%, after 60 min. The selective ET_B receptor antagonist, BQ-788, did not alter the PWV (change of –2 ± 6%, P = 0.8). Importantly, mean arterial pressure or heart rate did not change throughout any of the studies.

These results suggest that ET_B receptors are not involved in the regulation of arterial stiffness in vivo. Moreover, they confirm our previous findings in the ovine model that endothelin-1 acts predominantly via ET_A receptors to regulate arterial stiffness in vivo.