Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat

Renal blood flow (RBF) autoregulatory efficiency may be enhanced during NO inhibition in the rat, as recently reported. Under these conditions, endoth elin (ET) synthesis and release may be increased. Our purpose was therefore to determine the role of ET in RBF autoregulatory changes induced by NO in hibition. To address this point, ETA/B receptors were blocked in anesthetiz ed rats with bosentan, or selectively with BQ-610 or BQ-788. NO synthesis w as inhibited with N-G-nitro-L-arginine methyl ester (L-NAME). Mean arterial pressure (MAP) was decreased after bosentan (-10 mmHg; P < 0.01) or increa sed after L-NAME (25 mmHg; P < 0.001). RBF measured with an electromagnetic flow probe was reduced by L-NAME (-50%) and by BQ-788 (-24%). The pressure limits of the autoregulatory plateau (P-A similar to 100 mmHg) and of no R BF autoregulation (P-o similar to 80 mmHg) were significantly lowered by 15 mmHg after L-NAME but were unchanged after bosentan, BQ-610, or BQ-788. Du ring NO inhibition, autoregulatory resetting was completely hindered by bos entan (P-A similar to 100 mmHg) and by ETB receptor blockade with BQ-788 (P -A similar to 106 mmHg), but not by ETA receptor blockade with BQ-610 (P-A similar to 85 mmHg). These results suggest that the involvement of ET in th e RBF autoregulatory resetting occurs during NO inhibition, possibly by pre ferential activation of the ETB receptor. However, the relative contributio n of ET receptor subtypes remains to be further specified.