Abstract
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-1 H-azepinyl)]carbonyl]amino-4-methylpentanoyl]amino-3-(2-pyridyl) propionic acid (FR139317) (1 μg/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-γ-methylleucyl- d-1-methoxycarbonyltryptophanyl- d-norleucine (BQ-788) (1 μg/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.
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