Role of ET_B receptors and nitric oxide in adrenal catecholamine secretion in anesthetized dogs

Abstract

We examined the effects of sarafotoxin 6c (S6c), an endothelin-B (ET(B)) receptor agonist, on adrenal catecholamine secretion in response to cholinergic stimuli in pentobarbital sodium-anesthetized dogs. Drugs were administered intra-arterially into the adrenal gland through the phrenicoabdominal artery. Infusion of S6c attenuated increases in adrenal catecholamine output induced by splanchnic nerve stimulation. The inhibitory effect of S6c on the catecholamine secretion response was suppressed with a selective ET(B) receptor antagonist N-cis 2, 6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyl tryptophanyl-D-norleucine (BQ-788), a nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester, and a neuronal NOS inhibitor 7-nitroindazole monosodium salt (7-NINA). Similar results were obtained with the catecholamine secretion response induced by injection of ACh. 7-NINA alone did not affect these catecholamine secretion responses. These results suggest that ET(B) receptors play an inhibitory role in adrenal catecholamine secretion by activating neuronal NOS, whereas neuronal NOS is unlikely to be involved in regulation of adrenal catecholamine secretion in the absence of simultaneous ET(B) receptor stimulation.

Facilitatory role of NO in neural norepinephrine release in the rat kidney

“…In the isolated guinea pig atria, 7-NINA enhances positive chronotropic and inotropic responses induced by cardiac nerve stimulation but not the responses induced by exogenous NE (5), suggesting that NO produced by nNOS suppresses the neurotransmitter release. Recent work in our laboratory suggested that nNOS is responsible for endothelin-Breceptor-mediated suppression of the cholinergic adrenal catecholamine secretion in dogs (10). nNOS is also found in the rat kidney (22) and is considered to par-ticipate in the control of renal hemodynamics (11) and renin secretion (18).…”

Endothelin Signaling Pathways in Rat Adrenal Medulla

“…However, it has been shown that ET, acting as a paracrine and/or autocrine mechanism through the stimulation of ET B receptor-NO/cGMP pathway, is able to inhibit catecholamines secretion evoked by physiological activation of the nicotinic acetylcholine receptor present in the adrenal gland (Oset-Gasque et al, 1994;Hosokawa et al, 1999). Hence, it is probable that endothelin exerts a dual modulatory action through stimulation of ET B receptor: an inhibitory control of catecholamine release under conditions of high levels of stimulation of catecholamine secretion by acetylcholine and a stimulatory secretagogue action when ET is released as a paracrine hormone within the adrenal medulla.…”