Facilitation and inhibition by endothelin-1 of adrenal catecholamine secretion in anesthetized dogs

We examined the participation of endothelin ETA and ETB receptors in modula tion by endothelin-1 of adrenal catecholamine secretion during cholinergic activation in pentobarbital-anesthetized dogs. Drugs were infused intra-art erially into the adrenal gland. Splanchnic nerve stimulation (1 and 3 Hz) i ncreased adrenal catecholamine output in a frequency-dependent manner. Endo thelin-1 (0.2, 0.6, and 2 ng/kg/min) enhanced the catecholamine response in duced by the 3-Hz nerve stimulation. Under pretreatment with an endothelin ETA receptor antagonist (R)-2-[( R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]ca rbonyl]amino-4-methylpentolyl]amino-3-(2-pyridyl) propionic acid (FR139317) (1 mu g/kg/min), endothelin-1 suppressed the 1- and 3- Hz nerve stimulatio n-induced catecholamine response in a dose-dependent manner. No inhibitory or facilitatory effect of endothelin-1 was observed under simultaneous pret reatment with FR139317 and an endothelin ETB receptor antagonist N-cis 2,6- dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxy- carbonyltrypto phanyl-D-norleucine (BQ-788) (1 mu g/kg/min) or under pretreatment with BQ- 788 alone. These results suggest that in the dog adrenal gland, endothelin- 1 facilitates and inhibits adrenal catecholamine secretion during cholinerg ic activation by stimulating endothelin ETA and ETB receptors, respectively . (C) 2000 Elsevier Science B.V. All rights reserved.