Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats.

Abstract

Adrenal insufficiency in human and rat is associated with an impairment of the diuretic response to water load, and only glucorticoids (GCs) restore this deficit. Our observation that GCs potentiate atrial natriuretic polypeptide (ANP)-stimulated cGMP production in cultured renal cells prompted us to examine the possibility that GCs may restore the diuretic response through the potentiation of ANP action. Initially, changes in urine volume and ANP levels were studied in adrenalectomized (Adx) and sham-operated intact rats after an oral water load of 5 ml/100 g BW. Urine volume after water load was 4.5 +/- 0.5 ml/30 min in the intact rats, whereas it was 0.8 +/- 0.2 ml/30 min in the Adx rats. In the intact rats, a significant increase in plasma ANP level was observed 30 min after the water load, whereas no increase was observed in Adx rats. This defective ANP response may be involved in the impairment of the diuretic response in Adx rats. Indeed, pretreatment of Adx rats with dexamethasone (Dex, 20 micrograms/100 g BW) increased plasma ANP levels even before water load and improved diuretic response. Subsequently, effect of iv administration of human or rat ANP at a pharmacological dose (2.5 micrograms/100 g BW) on urine volume, osmolarity, and urinary excretion of cGMP, and sodium was studied in Adx rats that received an oral water load 30 min before ANP. Dex treatment was achieved by per os administration 3 h before the ANP injection. In Adx rats, the urine volume after ANP administration was 1.2 +/- 0.1 ml/30 min, and pretreatment with Dex markedly increased the urine volume to 6.3 +/- 0.4 ml/30 min. Dex also increased ANP-induced osmolar and sodium excretion by 2.6- and 2.9-fold, respectively. Although urinary excretion of cGMP was increased in Adx rats by ANP administration, a further significant increase was observed by the pretreatment with Dex. Injection of (Bu)2cGMP to Adx rats pretreated with Dex resulted in a significant increase in urine volume and osmolar and sodium excretion. However, no significant increase in urine volume was observed in Adx rats not pretreated with Dex. The present study suggests that GCs restore the diuretic response to acute water load not only by increasing the secretion of ANP but also by potentiating ANP-stimulated cGMP production. Furthermore, GCs may augment ANP action at one or more steps other than cGMP formation because administration of (Bu)2cGMP to Adx rats did not correct the diuretic response to water load.

Regulation of collecting duct AQP3 expression: response to mineralocorticoid

“…The observed decrease in urinary output is consistent with previous studies demonstrating that glucocorticoid deficiency is associated with an impaired water diuresis (19,23,29,41) and glucocorticoid treatment has been shown to restore this defect (29), partly by augmenting atrial natriuretic peptide (ANP) action (18). The impaired excretion of water by the kidney in glucocorticoid deficiency has been extensively investigated (1,16,19,24,29,41).…”

“…Adrenocortical hormones, glucocorticoid and mineralocorticoid, are importantly involved in the normal modulation of renal water excretion and regulation of ECF volume (23,29,37,41,42). Therefore, chronic adrenal insufficiency with depletion of adrenocortical hormones is associated with altered water and Na metabolism (40), e.g., an inability to excrete a water load in glucocorticoid deficiency (18,19,24) or increased urinary flow and natriuresis in aldosterone deficiency (44). Moreover, elevated vasopressin and ANG II levels secondary to the altered ECF volume status (29, 41) may also contribute to the change in water balance, e.g., an impairment of free water clearance and dilutional hyponatremia (43).…”

Updates on Veterinary Anatomy and Physiology

“…Cortisol also raises insulin concentrations in horses, but EC actions generally oppose but sometimes synergize with those of insulin [140]. For example, EC and insulin have opposite actions on blood glucose levels, as well as on appetite, gluconeogenesis, glucose transport, protein synthesis, muscle wastage, lipolysis, lipogenesis, and fat deposition in adipose tissue [141,142].…”