Abstract
We determined the antihypertensive effects of BQ-123 (cyclo(- d-Trp- d-Asp- l-Pro- d-Val- l-Leu-), sodium salt), a selective endothelin ET A 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.
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