Antihypertensive effects of BQ-123, a selective endothelin ETA receptor antagonist, in spontaneously hypertensive rats treated with DOCA-salt.

We determined the antihypertensive effects of BQ-123 (cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu-), sodium salt), a selective endothelin ETA receptor antagonist, in spontaneously hypertensive rats treated with deoxycorticosterone acetate-salt (DOCA-salt SHR). BQ-123 (1-30 mg/kg/h) decreased blood pressure in DOCA-salt SHR in a dose-dependent manner, although plasma immunoreactive endothelin-1 did not significantly increase and the maximal contractile response to endothelin-1 in the aorta significantly decreased as compared with values observed in age-matched SHR. These results suggest that endogenous endothelin-1 is involved in the maintenance of hypertension in DOCA-salt SHR, and that circulating endothelin-1 is not sufficient to reflect the physiological role of endothelin-1.