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

We examined the participation of endothelin ET(A) and ET(B) receptors in modulation by endothelin-1 of adrenal catecholamine secretion during cholinergic activation in pentobarbital-anesthetized dogs. Drugs were infused intra-arterially into the adrenal gland. Splanchnic nerve stimulation (1 and 3 Hz) increased adrenal catecholamine output in a frequency-dependent manner. Endothelin-1 (0.2, 0.6, and 2 ng/kg/min) enhanced the catecholamine response induced by the 3-Hz nerve stimulation. Under pretreatment with an endothelin ET(A) receptor antagonist (R)-2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-m eth ylpentanoyl]amino-3-(2-pyridyl) propionic acid (FR139317) (1 microg/kg/min), endothelin-1 suppressed the 1- and 3- Hz nerve stimulation-induced catecholamine response in a dose-dependent manner. No inhibitory or facilitatory effect of endothelin-1 was observed under simultaneous pretreatment with FR139317 and an endothelin ET(B) receptor antagonist N-cis 2, 6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-met hox ycarbonyl tryptophanyl-D-norleucine (BQ-788) (1 microg/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 cholinergic activation by stimulating endothelin ET(A) and ET(B) receptors, respectively.