Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus

Abstract

The hypothesis that nitric oxide plays a key role in the regulation of adrenal blood flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6‐0.8 of gestation, 11 llama fetuses were surgically prepared for long‐term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l‐NAME. Adrenal blood flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l‐NAME. Treatment with l‐NAME during normoxaemia led to a marked fall in adrenal blood flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline‐infused fetuses, acute hypoxaemia elicited an increase in adrenal blood flow and in plasma ACTH, cortisol, adrenaline and noradrenaline concentrations. Treatment with l‐NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in adrenal blood flow and in plasma cortisol and adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l‐NAME further enhanced the increase in fetal plasma noradrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of adrenal blood flow and adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus.

The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E 2

“…10C). Discussion NO has been postulated as an autocrine͞paracrine regulator of steroidogenesis in several tissues, with effects on adrenal steroid secretion (3,27,28). Our present results indicate that NO stimulates corticosterone release from adrenals in vitro.…”

Adrenocortical Suppression in Highland Chick Embryos Is Restored during Incubation at Sea Level

“…Our group (Riquelme et al, 1998;Riquelme et al, 2002) and Ducsay and Myers (Adachi et al, 2004;Imamura et al, 2004) have hypothesized that possible mechanisms exist to override suppression of fetal adrenocortical function during superimposed stress during development at high altitude. One strategy may be to increase acutely the gain of neural influences on adrenocortical function, which are triggered by a carotid chemoreflex (Riquelme et al, 1998;Riquelme et al, 2002) and mediated by splanchnic innervation to the adrenal gland (Myers et al, 1990).…”

“…Our group (Riquelme et al, 1998;Riquelme et al, 2002) and Ducsay and Myers (Adachi et al, 2004;Imamura et al, 2004) have hypothesized that possible mechanisms exist to override suppression of fetal adrenocortical function during superimposed stress during development at high altitude. One strategy may be to increase acutely the gain of neural influences on adrenocortical function, which are triggered by a carotid chemoreflex (Riquelme et al, 1998;Riquelme et al, 2002) and mediated by splanchnic innervation to the adrenal gland (Myers et al, 1990). Compared to sheep, such neural influences on adrenocortical ouput during acute stress in the fetus are sensitized in the llama (Riquelme et al, 1998;Riquelme, 2002), a species adapted to the chronic hypoxia of life at high altitude for generational times (Giussani et al, 1999).…”

“…One strategy may be to increase acutely the gain of neural influences on adrenocortical function, which are triggered by a carotid chemoreflex (Riquelme et al, 1998;Riquelme et al, 2002) and mediated by splanchnic innervation to the adrenal gland (Myers et al, 1990). Compared to sheep, such neural influences on adrenocortical ouput during acute stress in the fetus are sensitized in the llama (Riquelme et al, 1998;Riquelme, 2002), a species adapted to the chronic hypoxia of life at high altitude for generational times (Giussani et al, 1999). Ducsay and Myers have recently reported (Vargas et al, 2010) that the enhanced plasma cortisol response to a second stressor in the LTH sheep fetus may involve enhanced adrenocortical intracellular signaling downstream from cAMPdependent protein kinase A (PKA).…”

Down-regulation of adrenal neuronal nitric oxide synthase mRNAs and proteins after deoxycorticosterone acetate-salt treatment in rats

“…Besides, NO can regulate the rate of aldosterone and corticosterone production in adrenal glomerulosa [10] and fasciculata [12,13,27] cells. In addition to the modulation of NO on adrenocorticomedullary functions, NO is found to be capable to regulate adrenal blood flow [28]. Therefore, reduced adrenal NO synthesis secondary to decreased nNOS expression in DOCA-salt induced volume expansion state might contribute to dysregulation of adrenal function and to substantial reductions in resting flow rate to both medulla and cortex, and seemed to be a result of pre-hypertension in the rats.…”