Endothelin-1 enhances pressor responses to norepinephrine: involvement of endothelin-B receptor.

We investigated the effects of endothelin-1 (ET-1) on pressor responses to norepinephrine (NE) in perfused rat mesenteric arteries. Perfusion of the arteries with a subpressor dose of ET-1 (3 x 10(-10) M) for 15 min markedly enhanced the pressor responses to NE (10(-6) and 3 x 10(-6) M), and this effect was significantly prevented by BQ788 (10(-6) M) but not by FR139317 (10(-6) M). In DOCA-salt hypertensive rats, exogenous ET-1 had little effect on pressor responses to NE. Pressor responses to NE (10(-6) M) were significantly increased in DOCA-salt rats compared with those in normotensive rats. This increased response to NE was reduced to the level of normotensive rats by BQ788. FR139317 was without effect on the increased responses. These results suggest that ET-1 enhances contractile responses to NE through ETB receptors. Moreover, this phenomenon is stimulated tonically by endogenous ET-1 in DOCA-salt hypertensive rats and may contribute to the maintenance of hypertension in these rats.